Dissertations / Theses on the topic 'Nanoparticle treatment'
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1
Fisusi, F. A. "Nanoparticle based strategies for the treatment of glioblastoma." Thesis, University College London (University of London), 2014. http://discovery.ucl.ac.uk/1456357/.
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Glioblastoma is the most common and most biologically aggressive primary brain tumour in adults. In spite of tremendous investment into research which has led to the development and application of novel diagnostic and therapeutic measures in the management of glioblastoma, the prognosis is still dismal with median survival time of about 12 – 15 months. Also, the success of most cytotoxic drugs clinically employed in the treatment of glioblastoma is greatly limited by their dose-limiting toxicity which typically manifests as clinically significant reduction in blood cell counts. The aim of this study is to demonstrate that a high dose nanoparticle formulation of the cytotoxic drug lomustine using a self-assembling chitosan amphiphile, quaternary ammonium palmitoyl glycol chitosan would lead to improved survival outcomes without a commensurate increase in toxic effects. The novel nanoparticle based lomustine formulation employed in this study enabled the administration of a lomustine dose (13 mg kg-1) 10 times higher than the dose (1.2 mg kg-1) achievable with an ethanolic formulation of lomustine. Human glioblastoma tumour bearing mice treated with the high dose formulation had a mean survival time of 33.1 days while the mice treated with the low dose formulation had a mean survival time of 22.5 days after intravenous administration of the drug once daily for 10 consecutive days. The increased (1.5 times longer) survival time resulting from treatment with the nanoparticle based high dose formulation was not accompanied by an increase in gross toxic effects. Thus, the nanoparticle based formulation afforded the administration of lomustine in a continuous high dose schedule which led to beneficial therapeutic outcomes. In addition, three self-assembling peptide amphiphiles were synthesised and characterised for potential application in the transport and delivery of therapeutic molecules to the brain for the treatment of intracranial tumours.
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Wallat, Jaqueline Diane. "Fluorous Nanoparticle Platform for Cancer Imaging and Treatment." Case Western Reserve University School of Graduate Studies / OhioLINK, 2018. http://rave.ohiolink.edu/etdc/view?acc_num=case1513787381901888.
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Phelane, Lisebo. "Metal nanoparticle modified polysulfone membrane for water treatment." Thesis, University of the Western Cape, 2013. http://hdl.handle.net/11394/4480.
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>Magister Scientiae - MScMembrane separation processes have been widely applied in the treatment of wastewater with polysulfone (PSF) polymer membrane being the most frequently used in ultrafiltration of wastewater due to its chemical and structural stability and mechanical robustness. The disadvantage to these membranes is their hydrophobicity which leads to membrane fouling caused by organic pollutants in water. Many studies have been conducted to increase the hydrophilic properties of the polysulfone membrane surface. Most recently metal oxide nanoparticles have been introduced to the polymer matrix in order to reduce membrane fouling and increase its hydrophilicity with measurable success. Natural organic matters are the one of the major fouling agents during ultrafiltration, reverse osmosis and microfiltration. Two organic acids (Tannic Acid and Alginic Acid) were selected to test the fouling behaviour of nanometallic synthesised polysulfone membranes. For this study, polysulfone casting suspension was prepared by dissolving polysulfone beads in N,N-dimethly acetamide. Three metallic nanoparticles of Silver, Cobalt and Nickel were selected to improve the hydrophilicity of the polysulfone membrane. The metal nanoparticles were prepared using the chemical reduction method. Cobalt nanoparticles were synthesized by dissolving the cobalt chloride salt in deionized water and reduced with sodium borohydride at room temperature. The nickel chloride salt was dissolved in ethanol and reduced with sodium borohydride under magnetic stirrer. Silver nanoparticles were prepared by dissolving the silver nitrate in deionised water and heated to boil, the sodium citrate was added to reduced the silver nitrate. These nanoparticles were then integrated into the polysulfone polymer matrix to form the metal nanoparticle polysulfone nanocomposites. This study focused on four prepared polysulfone nanocomposite membrane; 1 unmodified polysulfone (PSF), 2 polysulfone modified with cobalt nanoparticles (PSF/Co), 3 polysulfone modified with nickel nanoparticles (PSF/Ni) and 4 polysulfone modified with silver nanoparticles (PSF/Ag).
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Peters, David Thomas. "Targeting atherosclerosis nanoparticle delivery for diagnosis and treatment /." Diss., Connect to a 24 p. preview or request complete full text in PDF format. Access restricted to UC campuses, 2009. http://wwwlib.umi.com/cr/ucsd/fullcit?p3339266.
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Thesis (Ph. D.)--University of California, San Diego, 2009.Title from first page of PDF file (viewed February 10, 2009). Available via ProQuest Digital Dissertations. Vita. Includes bibliographical references.
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Restis, Eva Marie. "Development of Drug Loaded Nanoparticles for Treatment of Mycobacterium avium Infection." Diss., Virginia Tech, 2014. http://hdl.handle.net/10919/52565.
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Currently, about one third of the world's population is latently infected with Mycobacterium tuberculosis and about 4 million people die from the disease annually worldwide. Although treatment with antimicrobials can be curative, many people fail to complete the prescribed therapeutic regimen which can increase the risk of disease re-emergence, spread of infection to others and development of drug resistance. An improved approach is urgently needed for patient compliance. Development of safe and effective colloidal drug delivery systems may reduce the amount and frequency of antimicrobial therapy needed. The major goal of this research effort is to explore the safety and efficacy of antimicrobial loaded nanoparticles against M. avium. Various in vitro efficacy studies were done with a) amikacin-loaded nanoparticles, b) clarithromycin-loaded nanoparticles, and c) with aerogel nanoparticles loaded with rifampicin, clarithromycin and ethambutol. Clarithromycin (CLA) and amikacin (AMK) loaded nanoparticles showed a significant reduction in viable M. avium compared to free antibiotics and untreated controls. Cytotoxicity assays revealed that all types of drug-laden nanoparticles were non-toxic to J774A.1 mouse macrophage cells at therapeutic doses. In vivo efficacy studies showed that only amikacin-loaded polymeric
nanoparticles improved clearance compared to free amikacin in M. avium infected BALB/c mice. In general, none of the nanoparticle formulations elicited any significant microscopic lesions in the organs of infected mice at tested doses. Each nanoparticle formulation was analyzed physicochemically for size, zeta potential, amount of drug load, minimum inhibitory concentration (MIC) and stability. Both the AMK and CLA polymeric nanoparticles were below 200 nm in size and had a slightly negative overall surface charge, aerogel nanoparticles were somewhat larger in size. The amount of drug load varied between all three nanoparticles and is largely dependent on the chemical structure and interactions between the nanoparticle and drug. The AMK and CLA nanoparticles were relatively stable under varying environmental conditions and time points and had MIC ranges equivalent to the respective free drugs.Ph. D.
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Andersson, Mikael. "Modeling and characterization of magnetic nanoparticles intended for cancer treatment." Thesis, Uppsala universitet, Fasta tillståndets fysik, 2013. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-199055.
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Cancer is one of the challenges for today's medicine and therefore a great deal of effort is being put into improving known methods of treatment and developing new ones. A new method that has been proposed is magnetic hyperthermia where magnetic nanoparticles linked to the tumor dissipate heat when subjected to an alternating magnetic field and will thus increase the temperature of the tumor. This method makes the tumor more susceptible to radiation therapy and chemotherapy, or can be used to elevate the temperature of the tumor cells to cause cell death. The particles proposed for this are single core and often have a size in the range of 10 nm to 50 nm. To achieve an effective treatment the particles should have a narrow size distribution and the proper size. In this work, a theoretical model for predicting the heating power generated by magnetic nanoparticles was evaluated. The model was compared with experimental results for magnetite particles of size 15 nm to 35 nm dissolved in water. The properties of the particles were characterized, including measurements of the magnetic saturation, the effective anisotropy constant, average size and size distribution. To evaluate the results from the model the AC susceptibility and heating power were experimentally determined. The model is a two-step model. First the out-of-phase component of the AC susceptibility as a function of frequency is calculated. Then this result is used to calculate the heating power. The model gives a correct prediction of the shape of the out-of-phase component of the susceptibility but overestimates its magnitude. Using the experimentally determined out-of-phase component of the susceptibility, the model estimation of the heating power compares quite well with the measured values.
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Wu, Xingchen. "Multiple sclerosis : MRI diagnosis, potential treatment and future potential for nanoparticle applications /." Stockholm, 2005. http://diss.kib.ki.se/2005/91-7140-515-1/.
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Lin, Kevin (Kevin Yu-Ming). "Nanoparticle systems that exploit host biology for diagnosis and treatment of disease." Thesis, Massachusetts Institute of Technology, 2014. http://hdl.handle.net/1721.1/98337.
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Thesis: Sc. D., Massachusetts Institute of Technology, Department of Chemical Engineering, 2014.Cataloged from PDF version of thesis.
Includes bibliographical references (pages 131-151).
Over the past 30 years, advances in nanotechnology have generated a multitude of nanostructures exhibiting a breadth of physical, chemical, and biological properties that have tremendous potential to improve the detection and treatment of disease. Despite this progress, biomedical nanotechnologies have yet to approach the same level of complexity as biological systems, which produce higher-order functions through coordinated interactions between multiple nanoscale components. This thesis aims to explore the potential of nanoparticles to interface with the host biology to perform systems-level applications that benefit disease sensing and treatment. First, we engineered nanoparticles to sense dysregulated protease activity associated with thrombosis and generate reporters that can be noninvasively quantified in the urine. These nanoparticles exploit the vascular transport of the circulatory system and the size filtration function of the renal system to emit reporters into the urine following proteolytic cleavage events. The reporter levels in the urine differentiate between healthy and thrombotic states and correlate with clot burden in a mouse model of pulmonary embolism. Next, we developed nanoparticles that homeostatically regulate the biological cascade responsible for haemostasis to prevent the aberrant formation of clots. These nanoparticles form a negative feedback loop with thrombin, a key enzyme in the coagulation cascade, to regulate their release of the anticoagulant heparin. In mice, they inhibited the formation of pulmonary embolisms without an associated increase in bleeding, the primary side-effect of antithrombotic therapy in the clinic. Finally, we investigated a two-component system whereby the first therapeutic entity induces the upregulation a molecular signal within a malignant environment to amplify the local recruitment of a secondary population of targeted nanoparticles. Here, the interaction between the initial therapeutic and the targeted nanoparticles occurred indirectly through a biological stress pathway. This cooperative targeting system delivered up to five-fold higher nanoparticle doses to tumors than non-cooperative controls, leading to delayed tumor growth and improved survival in mice. Together, these systems highlight the potential for interactive nanoparticle systems to perform highly complex functions in vivo by leveraging and modulating the host biology. In contrast to the current strategy of injecting large populations of nanoparticles that carry out identical, pre-defined tasks with little to no feedback from the in vivo environment, this work supports the construction of nanoparticle systems that leverage both synthetic and endogenous components to produce emergent behaviors for enhancing diagnostics and therapeutics.
by Kevin Lin.
Sc. D.
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Uppalapati, Lakshmi. "Peptides as therapeutics and active gene delivery vehicles for cancer treatment." Diss., Kansas State University, 2015. http://hdl.handle.net/2097/35231.
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Doctor of PhilosophyDepartment of Agronomy
Masaaki Tamura
Over the years proteins/peptides have evolved as promising therapeutic agents in the treatment of cancer. Considering the advantages of peptides such as their small size, ease of synthesis, tumor-penetrating ability and bio-compatibility, present report discusses proof of concept for 1. C1B5 peptide of protein kinase Cγ and a low dose of gemcitabine combination treatment for peritoneally disseminated pancreatic cancer and 2. dTAT peptide nanoparticles mediated gene (angiotensin II type 2 receptor gene) therapy for lung cancer. 1. A significant reduction in intraperitoneally (IP) transplanted pancreatic carcinoma growth was demonstrated with C1B5 peptide and gemcitabine co-treatment in an immunocompetent mouse model. Increased number of Granzyme B positive cells was observed in treated mice ascites, suggesting the involvement of immune response in tumor attenuation. The strong effect observed in combination treatment might be because of increase in lymphocyte recruitment by gemcitabine followed by C1B5 peptide mediated CD8+ T-cells or NK cells activation apart from direct cancer cell apoptosis. 2. To test dTAT peptide nanoparticles (dTAT NPs) mediated therapeutic gene delivery, luciferase reporter gene containing dTAT nanoparticles were synthesized (dTAT/pLUC/Ca2+). Synthesis conditions for nanoparticles were optimized based on dTAT/pLUC/Ca2+ nanoparticles transfection efficiency. With the optimized conditions, dTAT NPs containing AT2R, TRAIL or miR-34a pDNA (dTAT/pAT2R, dTAT/TRAIL or dTAT/miR- 34a) were synthesized. Therapeutic potential of these NPs was analyzed in lung adenocarcinoma containing mice by administering them intravenously (IV) or/and intratracheally (IV). Combination treatment with the IV injection of the new dTAT/pAT2R/Ca2+ formulation and the IT injection of the original dTAT/pAT2R/Ca2+ formulation is effective in attenuation of developed human bronchioloalveolar carcinoma in the SCID mouse lungs. Findings from the above mentioned studies have vital clinical relevance as it implies that peptides alone or when used as gene delivery systems may prove to be beneficial in the treatment of various stages of cancer.
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Seyedi, Seyed Mojtaba. "Engineered iron oxide nanoparticle-polymer composites for the removal of dissolved arsenic and antimony." Thesis, Edith Cowan University, Research Online, Perth, Western Australia, 2017. https://ro.ecu.edu.au/theses/2038.
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Dissolved metalloids, such as arsenic (As), antimony (Sb) and boron (B), are often found in contaminated surface waters or groundwater. Their removal is essential for protecting the water environment. This MEngSci research project investigated the use of magnetite (Fe3O4) nanoparticle – polymethylmethacrylate (PMMA) composites, as a reusable adsorbent toremove dissolved As andSb.
Comparative experiments were carried out to examine the effectiveness ofcommercial magnetite nanoparticles, lab synthesized nanoparticles, and the composites of synthesed Fe3O4nanoparticle-PMMA, for adsorbing As (III) and Sb (III) ions. The effects of major environmental and operating parameters (e.g. pH and adsorbent dosage) were investigated.Four cycles of adsorption-desorption experiment were conducted; the results demonstrating significant capability of the composites of removing the dissolved metalloids. In addition, the competitive adsorption of As and Sb to the composites was studied in batch experiments. It was found that the affinity of antimony to the adsorbents was generally greater than arsenic ions. A variety of analytical methods, such as X-Ray Diffraction (XRD), microwave plasma atomic emission spectrometry (MP-AES) and Malvern Zetasizer, were used to characterise the properties of the composites and analyze dissolved As and Sb concentrations. Details of the experimentalprocedures and results have been presented in this MEngSci thesis. Overall, this research validated: (a) a process to synthesize Fe3O4 nanoparticle-PMMA composites; and (b) the efficiency of using the composites to remove dissolved metalloids from contaminated water.
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Manohar, Nivedh Harshan. "Quantitative imaging of gold nanoparticle distribution for preclinical studies of gold nanoparticle-aided radiation therapy." Diss., Georgia Institute of Technology, 2015. http://hdl.handle.net/1853/54877.
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Gold nanoparticles (GNPs) have recently attracted considerable interest for use in radiation therapy due to their unique physical and biological properties. Of interest, GNPs (and other high-atomic-number materials) have been used to enhance radiation dose in tumors by taking advantage of increased photoelectric absorption. This physical phenomenon is well-understood on a macroscopic scale. However, biological outcomes often depend on the intratumoral and even intracellular distribution of GNPs, among other factors. Therefore, there exists a need to precisely visualize and accurately quantify GNP distributions. By virtue of the photoelectric effect, x-ray fluorescence (XRF) photons (characteristic x-rays) from gold can be induced and detected, not only allowing the distribution of GNPs within biological samples to be determined but also providing a unique molecular imaging option in conjunction with bioconjugated GNPs. This work proposes the use of this imaging modality, known as XRF imaging, to develop experimental imaging techniques for detecting and quantifying sparse distributions of GNPs in preclinical settings, such as within small-animal-sized objects, tissue samples, and superficial tumors. By imaging realistic GNP distributions, computational methods can then be used to understand radiation dose enhancement on an intratumoral scale and perhaps even down to the nanoscopic, subcellular realm, elucidating observed biological outcomes (e.g., radiosensitization of tumors) from the bottom-up. Ultimately, this work will result in experimental and computational tools for developing a better understanding of GNP-mediated dose enhancement and associated radiosensitization within the scope of GNP-aided radiation therapy.
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Sun, Lin. "Penetration evaluation and PLGA nanoparticle development of curcumin for topical delivery to treat psoriasis." Thesis, University of Macau, 2017. http://umaclib3.umac.mo/record=b3690807.
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Zibin, Hai. "Modification of Titania with Gold-Copper Bimetallic Nanoparticles and Preparation of Copper-Based Photocatalysts : Application in Water Treatment." Phd thesis, Université Paris Sud - Paris XI, 2013. http://tel.archives-ouvertes.fr/tel-00926757.
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Photocatalysis is recently extensively studied because it implies a variety of potential industrial applications ranging from the hydrogen generation of water splitting to the treatment of waste water. Among all the semiconductors, TiO2 has attracted the most attention. But the rate of the electron-hole recombinations is very important and TiO2 is active only under UV light. Various methods are developed to enhance the photoactivity of TiO2. Other semiconductors like copper oxides and copper sulfides also attracted attention due to their lower band-gaps which allow applications in solar photocatalysis. In this work, different kinds of photocatalysts were developed and studied: surface modified TiO2 with metal nanoparticles and copper sulfides and oxides. The nanostructures were characterized by different techniques: HRTEM, SEM, XRD, XPS, HAADF-SEM, and TRMC. Their photocatalytic activity was studied for degradation of model pollutants: phenol, rhodamine B and methyl orange. Different chemical and radiolytic methods have been investigated to modify the surface of TiO2 by mono- and bimetallic (Au, Cu and Au-Cu) nanoparticles in the aim to improve its photocatalytic activity. The best results in term of photocatalytic activity have been obtained with reduction of THPC (tetrakis (hydroxymethyl) phosphonium chloride) and with radiolytic reduction after deposition with urea. Titania surface modification with Au, Cu and bimetallic Au-Cu NPs enables the increase of the photocatalytic activity under UV light. We have found that very small amounts of metal (0.5% wt.) can activate titania for photocatalytic applications, thus the costs of photocatalyst preparation are relatively low. Radiolytic syntheses of non-TiO2 photocatalysts including Cu2O and CuS nanostructures with different morphologies have been developed. The photocatalytic activity of the synthesized photocatalysts has been studied. Truncated octahedral Cu2O exhibit an excellent photocatalytic activity under visible illumination. CuS nanotubes (NTs) exhibit both a high ability to adsorb dyes and a photocatalytic activity under visible light.
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Bielecki, Peter. "Advanced Mesoporous Silica Nanoparticles for the Treatment of Brain Tumors." Case Western Reserve University School of Graduate Studies / OhioLINK, 2020. http://rave.ohiolink.edu/etdc/view?acc_num=case159558503832021.
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Knapp, Christopher M. "Engineering siRNA Lipid Nanoparticles for the Treatment of Mantle Cell Lymphoma." Research Showcase @ CMU, 2017. http://repository.cmu.edu/dissertations/886.
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Mantle cell lymphoma (MCL) is an extremely difficult to treat subtype of non-Hodgkin lymphoma (NHL) with a low patient survival rate compared to most common cancers. Recently, nanoparticle delivery systems have received a great deal of interest for treating NHL. One of the more promising cargo options for these systems is short interfering RNA (siRNA). siRNA is a 18-23 nucleotide long double stranded RNA that is used to inhibit the protein expression of target mRNAs in a sequence specific manner. MCLs have several commonly overexpressed genes compared to normal cells making it an ideal candidate for siRNA therapies. For RNA interference to occur, A delivery vehicle is needed for the siRNA to reach the cytoplasm of the cell. In this thesis, ionizable lipid-like materials termed lipidoids are formulated into lipid nanoparticles (LNPs) to deliver siRNA. A new library of lipidoids is constructed to gain a better understanding of how the lipidoid tail-structure affects the silencing ability of LNPs. A novel tail precursor is identified as conferring potency to LNPs. Then, LNPs are used to silence genes within difficult to transfect MCL cells. LNPs targeting the anti-apoptotic protein Mcl-1 exhibit potent gene silencing and cause an increase in the fraction of cells undergoing apoptosis. This is important because there is no therapeutic that is FDA approved that targets this commonly overexpressed protein. Because of this LNP’s potency, siRNAs targeting multiple genes can be encapsulated into LNPs without causing unwanted toxicity. LNPs targeting several genes in multiple pathways cause a larger fraction of MCL cells to undergo apoptosis compared to cells treated with LNPs targeting only one gene. A major issue in cancer therapeutics is that the majority of nanoparticles accumulate in the liver. In an effort to improve the delivery of LNPs to target cells, changes to their formulations and administration methods are investigated as a means to improve LNP circulation time, biodistribution, and silencing ability. Overall, this work identifies lipidoid nanoparticles as potent siRNA delivery systems to treat MCL and investigates key properties for further improvement in LNP siRNA delivery to target cells.
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Abedin, Farhana. "Magnetic and albumin targeted drug delivery for breast cancer treatment." Thesis, Wichita State University, 2011. http://hdl.handle.net/10057/5054.
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This research work involves multifunctional magnetically targeted drug delivery
microspheres for treatment against breast cancer. A combination therapy approach was followed
by encapsulating two chemotherapeutics, 5-Fluorouracil (5-Fu) and cyclophosphamide in
poly(D, L-lactide-co-glycolide) (PLGA) microspheres. Magnetite nanoparticles and albumin
were also incorporated in the microspheres to achieve targeted treatment. The microspheres were
fabricated using oil-in-oil emulsion/solvent evaporation technique. Albumin is attracted to cancer
cells and thus it is likely to draw the microspheres towards tumor cells. On application of
magnetic field near tumor site, magnetites in the microspheres are likely to guide them to the
region of magnetic field. This will allow release of drugs from microspheres in the cancer cells.
Also the burst release of drugs and then slow release due to diffusion in the cancer cells lead to
effective treatment and also limit excessive spreading of drugs in other regions of the body.
Release rate study was carried out using high performance liquid chromatography (HPLC). Invitro
and in-vivo study was carried out to check the efficacy of treatment.Thesis (M.S.)--Wichita State University, College of Engineering, Dept. of Mechanical Engineering.
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Stigliano, Robert Vincent. "Development and validation of a treatment planning model for magnetic nanoparticle hyperthermia cancer therapy." Thesis, Dartmouth College, 2014. http://pqdtopen.proquest.com/#viewpdf?dispub=1566731.
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The use of magnetic nanoparticles (mNPs) to induce local hyperthermia has been emerging in recent years as a promising cancer therapy, in both a stand-alone and combination treatment setting, including surgery radiation and chemotherapy. The mNP solution can be injected either directly into the tumor, or administered intravenously. Studies have shown that some cancer cells associate with, internalize, and aggregate mNPs more preferentially than normal cells, with and without antibody targeting. Once the mNPs are delivered inside the cells, a low frequency (30-300kHz) alternating electromagnetic field is used to activate the mNPs. The nanoparticles absorb the applied field and provide localized heat generation at nano-micron scales.
Treatment planning models have been shown to improve treatment efficacy in radiation therapy by limiting normal tissue damage while maximizing dose to the tumor. To date, there does not exist a clinical treatment planning model for magnetic nanoparticle hyperthermia which is robust, validated, and commercially available. The focus of this research is on the development and experimental validation of a treatment planning model, consisting of a coupled electromagnetic and thermal model that predicts dynamic thermal distributions during treatment.
When allowed to incubate, the mNPs are often sequestered by cancer cells and packed into endosomes. The proximity of the mNPs has a strong influence on their ability to heat due to interparticle magnetic interaction effects. A model of mNP heating which takes into account the effects of magnetic interaction was developed, and validated against experimental data. An animal study in mice was conducted to determine the effects of mNP solution injection duration and PEGylation on macroscale mNP distribution within the tumor, in order to further inform the treatment planning model and future experimental technique. In clinical applications, a critical limiting factor for the maximum applied field is the heating caused by eddy currents, which are induced in the noncancerous tissue. Phantom studies were conducted to validate the ability of the model to accurately predict eddy current heating in the case of zero blood perfusion, and preliminary data was collected to show the validity of the model in live mice to incorporate blood perfusion.
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Sagar, Vidya. "Magnetic Nanoparticle-based Targeted Drug Delivery for Treatment of Neuro-AIDS and Drug Addiction." FIU Digital Commons, 2013. http://digitalcommons.fiu.edu/etd/909.
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Brain is one of the safe sanctuaries for HIV and, in turn, continuously supplies active viruses to the periphery. Additionally, HIV infection in brain results in several mild-to-severe neuro-immunological complications termed neuroAIDS. One-tenth of HIV-infected population is addicted to recreational drugs such as opiates, alcohol, nicotine, marijuana, etc. which share common target-areas in the brain with HIV. Interestingly, intensity of neuropathogenesis is remarkably enhanced due to exposure of recreational drugs during HIV infection. Current treatments to alleviate either the individual or synergistic effects of abusive drugs and HIV on neuronal modulations are less effective at CNS level, basically due to impermeability of therapeutic molecules across blood-brain barrier (BBB).
Despite exciting advancement of nanotechnology in drug delivery, existing nanovehicles such as dendrimers, polymers, micelles, etc. suffer from the lack of adequate BBB penetrability before the drugs are engulfed by the reticuloendothelial system cells as well as the uncertainty that if and when the nanocarrier reaches the brain. Therefore, in order to develop a fast, target-specific, safe, and effective approach for brain delivery of anti-addiction, anti-viral and neuroprotective drugs, we exploited the potential of magnetic nanoparticles (MNPs) which, in recent years, has attracted significant importance in biomedical applications. We hypothesize that under the influence of external (non-invasive) magnetic force, MNPs can deliver these drugs across BBB in most effective manner. Accordingly, in this dissertation, I delineated the pharmacokinetics and dynamics of MNPs bound anti-opioid, anti-HIV and neuroprotective drugs for delivery in brain. I have developed a liposome-based novel magnetized nanovehicle which, under the influence of external magnetic forces, can transmigrate and effectively deliver drugs across BBB without compromising its integrity. It is expected that the developed nanoformulations may be of high therapeutic significance for neuroAIDS and for drug addiction as well.
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Зленко, Віталій Олександрович, Виталий Александрович Зленко, Vitalii Oleksandrovych Zlenko, Максим Геннадійович Демиденко, Максим Геннадьевич Демиденко, Maksym Hennadiiovych Demydenko, Сергій Іванович Проценко, Сергей Иванович Проценко, and Serhii Ivanovych Protsenko. "Magneto-optical Studying of Magnetic Nanoparticle Arrays, Obtained by Thin Metal Films Thermal Treatment." Thesis, Sumy State University, 2015. http://essuir.sumdu.edu.ua/handle/123456789/40953.
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Magnetic nanoparticle assemblies were obtained using thermal annealing of thin Co films (initial effective film thickness 1,5-1,8 nm), condensed by thermal evaporation on Si3N4/Si substrates. After condensation samples were annealed (T = 1020 K) in vacuum (residual gas pressure P = 10 – 7 Pa).
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HE, PENG. "DEPOSITION OF EXTREMELY THIN FUNCTIONAL FILMS ON NANOPARTICLE/NANOTUBE SURFACES BY A PLASMA TREATMENT." University of Cincinnati / OhioLINK, 2003. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1068676591.
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Wen, Wucheng. "Development and Evaluation of Nano-herbal Therapy for Metastatic Breast Cancer Treatment." Diss., Temple University Libraries, 2018. http://cdm16002.contentdm.oclc.org/cdm/ref/collection/p245801coll10/id/534260.
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Pharmaceutical SciencesPh.D.
Triptolide (TPL), a diterpenoid triepoxide that is extracted from a traditional Chinese herb called Tripterygium Wilfordii (also known as ‘Thunder God Vine’) has recently drawn increasing interests from pharmaceutical and biomedical researchers, especially in the aspect of its potential efficacy on multiple cancer treatment. TPL has shown significant growth and proliferation inhibition activities in a broad range of cancer cell types. Moreover, it has shown the inhibition of osteoclastogenesis by breast cancer bone metastasis. However, due to its limitation in toxicity, solubility and non-specific biodistribution, it is challenging for the application of TPL in clinical study. Besides, TPL can rapidly distribute in most vital organs and no evidences shown tissue accumulation of drug. It is indispensable to overcome those barriers and optimize the properties and performance of the promising drug molecule. Lipid-based nanocarriers such as nanostructured lipid carriers (NLC) have been extensively studied for delivery of poorly-water soluble drug compounds. They also have the potential to optimize the physicochemical properties of the drug and may enhance a targeted delivery of the drug to specific therapeutic site. Alendronate (Fosamax®), an FDA approved bisphosphonate drug for osteoporosis, osteogenesis imperfecta and several other bone diseases, has been used as a bone targeting decoration agent. Breast cancer cell line MDA-MB-231 and other type of cancer cell lines have been used to study the in vitro cytotoxicity of TPL and the carriers while MC3T3-E1 cell line was used for toxicity assessment. Rats have also been used to study the in vivo performance of the drug. After modifying and optimizing the formulation of the particle, the formulation had the ability to remain structurally and functionally stable when being in the bio-simulated media at 37 °C and in water at room temperature with high encapsulation efficiency. In vitro study illustrated that both TPL free drug (stock solution 10mg/mL dissolved in DMSO) and TPL nanoparticle without alendronate (TPL-NP) had similar cytotoxicity on MDA-MB-231 and some other type of cancer cell lines. The ALE decoration on the particle (ALE-NP-TPL) has enhanced the anti-cancer effect especially with breast cancer cell line. The in vivo study shows that after 24 hours of the dose injection at local bone site, the formulation and TPL can remained at the location without random distribution to other organs. TPL-NP has not only successfully optimized the physicochemical properties of the drug, but also shows great enhancement of therapeutic effect both in vitro and in vivo study.
Temple University--Theses
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Lee, Kate Y. J. "Colloidal gold nanoparticles for cancer therapy: effects of particle size on treatment efficacy, toxicology, and biodistribution." Diss., Georgia Institute of Technology, 2011. http://hdl.handle.net/1853/43640.
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Gold nanoparticle has emerged as an attractive platform for drug delivery applications by complementing the existing drug delivery carriers. Currently, only a few gold nanoparticle-based anticancer drug delivery systems have been reported, compared to the polymer-based delivery systems. Additionally, there is still a lack of understanding for the behavior and fate of the gold-drug conjugate in the body that further attention is required. The overall goal of this thesis is to investigate the in vivo behavior of colloidal gold nanoparticle and its therapeutic efficacy in an animal model, especially in a drug delivery application. To achieve this goal, we investigated the feasibility of using colloidal gold nanoparticle as an anticancer agent delivery vehicle for treatment of cancer. Then, long-term clearance, toxicity, and biodistribution of colloidal gold nanoparticle were studied to further aid in understanding of using colloidal gold nanoparticle as a drug delivery platform. In particular, two representative sizes of gold nanoparticles, 5nm and 60nm, were investigated for the size effect on the therapeutic efficacy, toxicity, biodistribution, and clearance in cancer nanotherapy.
We believe that nanoparticle size plays a critical role in not only delivering the drug to the target site but also determining the in vivo behavior such as biodistribution and clearance. By choosing an appropriate size scale for the system, we successfully used the small-sized gold nanoparticles for drug delivery applications, which also displayed no apparent toxicity with desirable clearance from the biological system. This work is significant by providing an insight on a potential ideal candidate for drug delivery carrier for cancer nanotherapy.
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Shirkhani, Khojasteh. "Bioactivity of new AmB-PMA nanoparticle in prophylaxis and treatment of transplant-related invasive aspergillosis." Thesis, Imperial College London, 2014. http://hdl.handle.net/10044/1/24157.
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Aspergillus species are opportunistic mould pathogens that can cause a wide variety of pulmonary diseases. They are mainly caused by Aspergillus fumigatus (Munoz et al., 2006). Germination of conidia in hosts with a susceptible immune system is the first step in Aspergillus infection, and invasive aspergillosis (IA) is a major cause of mortality in transplant patients. Due to the increased occurrence of IA in high-risk populations, prophylaxis against IA is important. Prophylactic prevention of life threatening infections with drugs is now the preferred clinical strategy for these patients rather than treating the disease after it has become established. Inhaled amphotericin B (AmB) has potential for preventing IA and it has been reported to decrease the incidence of IA in solid organ transplant patients (Arthur et al., 2004). I have generated a new respiratory formulation of AmB (AmB-PMA) with a commercially available high purity, low polydispersity and non-toxic poly methacrylic acid sodium salt (PMA-Na). The chemical synthesis was optimized and showed that AmB-PMA complex was effective against A. fumigatus and was also less toxic than Fungizone in-vitro. The efficacy of AmB-PMA was determined in-vivo in BALB/c and C57BL/6 mice. Mice were infected intranasally with A. fumigatus CEA10 and treated with AmB-PMA by the nasal and nebulisation routes. In this thesis, the optimum routes of in-vivo administration, dosing regimens and treatment frequency were defined. Disease progression in A. fumigatus-infected BALB/c and C57BL/6 mice was monitored by histology, qPCR analysis of chemokine and cytokine responses in mouse lung, colony forming unit (CFU) and qPCR for Aspergillus ribosomal 28S rRNA. The results showed a significant reduction in CFU and DNA fungal load in AmB-PMA infected mice as compared to infected untreated mice. In addition, AmB-PMA could also affect cytokine production by increasing IFN-γ production and reducing MIP-1β, TNF-α and IL-10 as compared to infected untreated mice. However, the increase in IFN-γ production was not statistically significant when compared to infected untreated mice. My thesis demonstrates that a new low-cost AmB based PMA-Na polymer antifungal drug can be successfully given by the aerosol route to immuno-suppressed mice by nebulisation to prevent IA.
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Cover, Natasha Faith. "A Novel Device and Nanoparticle-Based Approach for Improving Diagnosis and Treatment of pelvic Inflammatory Disease." Scholar Commons, 2012. http://scholarcommons.usf.edu/etd/4020.
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Pelvic Inflammatory Disease (PID) is one of the most common causes of morbidity in women. PID is a polymicrobial infection of the female reproductive tract, and is associated with pelvic pain, abnormal uterine bleeding, and tubal damage that can lead to ectopic pregnancies and infertility. It is curable but the effects of PID can be permanent if not properly diagnosed and treated. PID presents as a spectrum of disease and is often missed at early stages; even acute PID can be difficult to diagnose, as there is no single conclusive diagnostic test. Currently, PID is identified and treated syndromically because pelvic pain is the only consistent clinical finding. The Center for Disease Control and Prevention (CDC) recommends doxycycline, a broad-spectrum antibiotic, for treatment but doxycycline can cause gastrointestinal irritation and local inflammation leading to an incomplete treatment. Most cases of PID are polymicrobial infections of the tubes and endometrium, which are not accessible to culture due to the difficulty of procuring samples above the naturally contaminated vagina and distal cervix. Given the difficulty of properly diagnosing PID and the limitations and side effects of the current treatments, there is an urgent need for new approaches for improving the accuracy for diagnosis and treatment of PID. We propose a new and practical approach to collect sterile specimen samples from the endometrium for more accurate PID diagnosis, and to treat the reproductive tract locally using doxycycline-loaded nanoparticles. The proposed research presents a novel sterile uterine sampler cover (SUSC) device that can safely and effectively collect uncontaminated specimen samples from the uterus, and also deliver nano-encapsulated drugs directly to the site of infection. The analysis of uncontaminated endometrium samples is expected to provide an understanding of uterine flora in symptomatic and asymptomatic women, and will lead to the identification of infective microbes in symptomatic women for pathogen-specific treatment. The use of nano-encapsulated doxycycline will enable localized drug delivery to lower drug dosage and minimize side effects for the patient. The doxycycline-loaded nanoparticles are characterized and evaluated based on their drug release properties, size distribution, and tissue response in vitro. This research will lead towards a more effective approach for the diagnosis and treatment of PID while freeing women from prolonged systemic treatments and their adverse effects. Moreover, this research will increase our understanding of the uterine biome under various hormonal and pathologic conditions, in symptomatic and asymptomatic women.
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Papa, Simonetta Giulia. "Characterization of a Nanoparticle Drug Delivery System for the Treatment of Inflammation in Spinal Cord Injury." Thesis, Open University, 2017. http://oro.open.ac.uk/48334/.
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Spinal cord injury (SCI) results from a mechanical primary injury that is followed by a multifactorial secondary injury which worsens the clinical course. Persistent inflammation is a crucial event during the secondary injury. Indeed, microglia/macrophage respond to traumatic stimuli by adopting an activated phenotype, which has a dual role. An M1 phenotype, associated with harmful effects, is expressed very early and persists for a long time in the injured site, whereas M2, associated with a beneficial phenotype, has only a transient expression in a subacute phase of the trauma. This suggests that microglia/macrophage mediated inflammation is a crucial therapeutic target. Nanoparticles (NPs) are selectively engulfed by microglia/macrophage as part of their endocytic/phagocytic activity in removing foreign bodies. Microglia assume phagocytic activity after traumatic stimuli and this makes NPs an excellent tool for carrying drug to these cells. So, in order to counteract this deleterious pro-inflammatory response, we decided to maximize the efficacy of a well-known anti-inflammatory drug, minocycline, through a NPs delivery tool selectively targeted to microglia/macrophage. We developed and tested a new drug delivery nanocarrier (minocycline loaded in poly-ε-caprolactone NPs, PCL Mino) in vitro and in vivo. Specifically, we demonstrated a reduced activation of microglia/macrophage after PCL Mino treatment in vitro and a reduction of cells with phagocytic-like phenotype, up to 15 days tested in vivo. To clarify the involvement of the inflammatory response associated to microglia/macrophage in SCI progression, we treated SCI mice in acute and subacute phase. PCL Mino treatment, only when administered acutely after the damage, was able to ameliorate the locomotor activity up to 63 days post injury. Furthermore, we demonstrated that this treatment reduced M1 macrophages recruitment orchestrated by activated microglial cells via CCL2 chemokine in the damaged site, suggesting a deleterious effect in the early phase of the injury of these cells. In conclusion, this delivery tool represents a new hope for SCI treatment by showing several advantages compared to conventionally administered anti-inflammatory therapy, such as maximization of therapeutic efficiency and reduction of side effects. Furthermore, the potential of transfer to clinical practice is aided by the large clinical use of minocycline and the high biocompatibility of the proposed NPs.
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Mapukata, Sivuyisiwe. "Photocatalytic treatment of organic and inorganic water pollutants using zinc phthalocyanine-cobalt ferrite magnetic nanoparticle conjugates." Thesis, Rhodes University, 2019. http://hdl.handle.net/10962/67603.
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This work explores the synthesis and photophysicochemical properties of zinc phthalocyanines when conjugated to cobalt ferrite magnetic nanoparticles. Phthalocyanines with amine and carboxylic acid functional groups were synthesised so as to covalently link them via amide bonds to cobalt ferrite magnetic nanoparticles with carboxylic acid and amine groups, respectively. Spectroscopic and microscopic studies confirmed the formation and purity of the phthalocyanine-cobalt ferrite magnetic nanoparticle conjugates which exhibited enhanced triplet and singlet quantum yields compared to the phthalocyanines alone. The studies showed that the presence of cobalt ferrite nanoparticles significantly lowered fluorescence quantum yields and lifetimes. The conjugates not only showed much higher singlet oxygen quantum yields compared to the phthalocyanines alone but were also attractive because of their magnetic regeneration and hence reusability properties, making them appealing for photocatalytic applications. The photocatalytic ability of some of the phthalocyanines and their conjugates were then tested based on their photooxidation and photoreduction abilities on Methyl Orange and hexavalent chromium, respectively. For catalyst support, some of the zinc phthalocyanines, cobalt ferrite magnetic nanoparticles and their respective conjugates were successfully incorporated into electrospun polystyrene and polyamide-6 fibers. Spectral characteristics of the functionalized electrospun fibers confirmed the incorporation of the photocatalysts and indicated that the phthalocyanines and their respective conjuagates remained intact with their integrity maintained within the polymeric fiber matrices. The photochemical properties of the complexes were equally maintained within the electrospun fibers hence they were applied in the photooxidation of azo dyes using Orange G and Methyl Orange as model organic compounds.
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Dyne, Eric D. "Magnetic Nanoparticle Hyperthermia-Mediated Clearance of Beta-amyloid Plaques: Implications in the Treatment of Alzheimer’s Disease." Kent State University / OhioLINK, 2021. http://rave.ohiolink.edu/etdc/view?acc_num=kent1618706341759415.
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Guo, Pengbo. "Bone targeting nanoparticle as a new platform of antibiotic agent delivery for the treatment of osteomyelitis." Diss., Temple University Libraries, 2019. http://cdm16002.contentdm.oclc.org/cdm/ref/collection/p245801coll10/id/577034.
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Pharmaceutical SciencesPh.D.
Osteomyelitis is a bone infection disease that is caused by microbes. One of the reason that a successful antimicrobial therapy has not been achieved in bone related infection is due to the physiological and structural limitations and multi-drug resistant bacteria, such as methicillin-resistant Staphylococcus aureus (MRSA). Alendronate, a type of bisphosphonate, is a commonly used drug to treat osteoporosis that can strongly chelate with the calcium ions in bone mineral (hydroxyapatite), could be utilized as an active targeting moiety in a drug delivery system to bone tissues. Since nanomedicine can provide a robust drug delivery platform, with the properties of encapsulating molecules of different hydrophilicity, tunable drug release profile, and potential of differential targeting cells and tissues, we proposed a lipid-polymer nanoparticle system, Bone-Targeting Nanoparticle (BTN), with surface modified with covalently bonded alendronate. In this study, BTN encapsulates linezolid, which has dose-related adverse effect that prevent long duration usage. According to our current results, BTN demonstrates three distinguished traits that potentially improves the therapeutic effect of linezolid towards MRSA induced osteomyelitis: a) a hydrophobic polymeric core that can encapsulate a high amount of linezolid; b) alendronate as a targeting moiety that can guide BTN to bone tissue and accumulate near the site of infection; and c) a PEGylated lipid interface that can enhance the drug release profile and provide increased serum stability relative to standard delivery methods.
Temple University--Theses
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Kennell, Carly M. "Synthesis and Characterization of Hybrid Co-Delivery Nanoparticles for Triple Negative Breast Cancer Treatment." University of Cincinnati / OhioLINK, 2016. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1470741290.
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Stolzoff, Michelle L. "Designing the surface properties of expansile nanoparticles for targeted cancer therapy." Thesis, Boston University, 2013. https://hdl.handle.net/2144/21256.
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Thesis (M.Sc.Eng.) PLEASE NOTE: Boston University Libraries did not receive an Authorization To Manage form for this thesis or dissertation. It is therefore not openly accessible, though it may be available by request. If you are the author or principal advisor of this work and would like to request open access for it, please contact us at open-help@bu.edu. Thank you.Nanoparticle-based drug delivery has been explored to circumvent the often-toxic chemotherapy treatments used today by providing a more efficient and specific delivery to diseased tissues. Recently we have developed polymeric pH-responsive expansile nanoparticles (eNPs) for intracellular delivery of paclitaxel (Pax) as an improvement upon the traditional methods of delivery of Pax with using Cremophor/ethanol. As eNPs are internalized by the cell, the hydrophobic protecting groups found on side chains along the polymer backbone are hydrolyzed, leaving behind hydrophilic moieties that cause the eNPs to slowly swell with water. In this manner, the encapsulation and controlled release of a hydrophobic drug can be achieved. By altering the surface characteristics of the eNPs, one can change the behavior of the delivery vehicle as well as the biological response. To explore this approach, two surfactant strategies were employed. Specifically, the original sodium dodecyl sulfate (SDS) surfactant has been substituted with PEGylated surfactants (either lipids or poloxamer) to improve circulation and in vivo stability. In addition, these surfactants were functionalized to target the folate receptor (FR), which is overexpressed in several cancers, in order to increase cancer cell-specific localization and uptake. The resulting eNPs retained their swelling characteristics while demonstrating improved cellular uptake in folate receptor-expressing KB and MDA-MB-231 carcinoma cells with no change in uptake in A549 cells, which do not express the folate receptor.
2031-01-01
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Zamora, Pérez Paula 1988. "Gold nanoparticle-modified polyelectrolyte nanocapsules as luminescent and photothermal agents for the local treatment of cutaneous melanoma." Doctoral thesis, TDX (Tesis Doctorals en Xarxa), 2021. http://hdl.handle.net/10803/671605.
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Gold nanoparticle-modified polyelectrolyte nanocapsules present unique properties that allow them to generate luminescence and heat through exposure to light. Moreover, gold is a material extensively studied in biomedicine for its stability and safety. This Thesis proposes the application of gold nanoparticle-modified nanocapsules as multifunctional agents for the localized treatment of cutaneous melanoma. This platform also permits the incorporation of therapeutic/imaging agents for the development of advanced nanotherapies.
This Thesis has investigated the cell-nanocapsules interactions in terms of particle concentration, internalization, oxidative stress and hypoxia, demonstrating their non-toxic profile. Melanoma cells internalize nanocapsules after 24 h of exposition, being localized inside acidic lysosomes preserving their structure and resisting degradation. The heat produced upon photothermal therapy of cell models (λ=830 nm) resulted in disintegration of the nanocapsules and cellular necrosis. Through photothermal control, oxidative stress and programmed cell death were observed. Thanks to their luminescent properties (λ=830 nm), a relationship between particle concentration and anti-tumoral photothermal efficiency was established. Photothermal therapy of melanoma tumors in mice (λ=806 nm), resulted in tumoral complete reduction. Moreover, the intratumoral administration of the nanocapsules avoided systemic particle biodistribution, being eliminated principally with the necrotic tissue formed after treatment. The nanocapsules’ distribution required for photothermal success was achieved 24 hours after administration in melanoma tumors grown for 5 days. In conclusion, gold nanoparticle modified nanocapsules are promising agents for the selective treatment of superficial solid tumors such as melanoma.Las nanocápsulas de polielectrolitos modificadas con nanopartículas de oro presentan propiedades únicas, que les permiten generar luminiscencia y calor mediante exposición a luz. Además, el oro es un material extensivamente estudiado en biomedicina por su estabilidad y seguridad. Esta Tesis propone la aplicación de nanocápsulas de polielectrolito modificadas con nanopartículas de oro, como agentes multifuncionales para el tratamiento localizado del melanoma cutáneo. Esta plataforma, además, permiten la incorporación de agentes terapéuticos/diagnósticos para el desarrollo de nanoterapias avanzadas. Esta Tesis ha investigado la interacción célula-nanocápsula en términos de concentración, internalización, estrés oxidativo e hipoxia, demostrando su perfil biocompatible. Las células de melanoma internalizan las nanocápsulas tras 24 h de exposición, pudiendo localizarlas en lisosomas (ácidos) preservando su estructura y resistiendo la degradación. El calor producido tras el tratamiento fototérmico de modelos celulares (λ=830 nm) resultó en la desintegración tanto de las nanocápsulas como de la estructura celular (necrosis). Mediante el control de la temperatura, se observó inducción de estrés oxidativo y muerte celular programada (apoptosis). Gracias a sus propiedades luminiscentes (λ=830 nm), se pudo relacionar cantidad de nanocápsulas con la eficiencia antitumoral de la terapia fototérmica in vitro. El tratamiento fototérmico de melanomas in vivo (λ=806 nm), resultó en una reducción tumoral completa. Además, la administración intratumoral de las nanocápsulas evitó su distribución sistémica, siendo eliminadas principalmente con el tejido necrótico formado tras el tratamiento. La distribución de las nanocápsulas tras 24 horas post-administración, fue óptima para el éxito del tratamiento fototérmico en melanomas de 5 días de crecimiento. Todo ello hace de las nanocápsulas, un agente fototérmico prometedor para el tratamiento selectivo de tumores sólidos superficiales como el melanoma.
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Huang, Wei. "Assembly, characterization and evaluation of a 3rd generation nanoparticle based drug carrier for metastatic breast cancer treatment." Diss., Virginia Tech, 2013. http://hdl.handle.net/10919/50932.
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Cancer is one of the leading causes of death in the world. For women in the U.S. and the European countries, breast cancer is the most common type and it continuously threatens the lives of the patients and causes huge economic losses. Chemotherapy and endocrine therapy are the common treatments for recurrence prevention and metastatic cancer symptom palliation. However, the uses of these therapies are meanwhile largely limited because their toxic side effects and non-specificity usually lead to low quality lives of the patients. Low aqueous solubility, multi-drug resistance, degradation of drug, limited intra-tumor diffusion and etc. are other limitations of conventional chemotherapies and endocrine therapies.
Nanoparticle based drug carriers were extensively studied for therapeutic drug delivery. Many carriers could be loaded with high dose of hydrophobic and hydrophilic drugs, protect the drug from the surrounding in vivo environment during the transportation, specifically target and enter the tumor cells and slowly release the drug thereafter. Advanced nanoparticle drug carriers are studied driven by the need of a more efficient drug delivery. The 3rd generation of nanoparticle based drug carriers are recently developed. They usually consist of more than one type of nanoparticles. Different part of the particle has more specialized functions. Therefore, by carefully selecting from the conventional nanoparticle carriers, a 3rd generation particle could have the properties such as high loading capacity of multiple drugs, prolonged half-life in circulation, higher tendency of accumulating at the tumor site, improved specificity to the tumor cells, higher cell uptake rate and accurately triggered controlled release, and combination of the above-mentioned properties.
In our study, a paclitaxel loaded nanoparticle supported immunoliposome was assembled for metastatic breast cancer drug delivery. Functionalized single walled carbon nanohorn or poly(lactic-co-glycolic acid) was encapsulated in the polyethylene glycol (PEG) coated liposome for high drug loading and controlled release. Anti-Her2 antibody or Herceptin® was grafted onto the surface of the liposome for a higher affinity to the Her2 overexpressing breast cancer cells.
Firstly, the conjugation of protein to the surface of liposome and PEGylated liposomes were investigated. Proteins with or without membrane binding domain were conjugated to liposome and PEGylated liposomes through covalent and non-covalent binding for comparison. A modified enzyme-linked immune sorbent assay was developed for surface grafted protein quantification.
Secondly, the encapsulation of solid nanoparticle into PEGylated immunoliposome was investigated. Results showed a new structure of solid nanoparticle in PEGylated immunoliposome at a 1:1 ratio was formed during the repeated freeze-thawing process. Supported immunoliposomes with high homogeneity in size and structure were purified by sucrose density gradient centrifugation.
Thirdly, the drug loading, triggered release, cell binding, cell uptake and cell toxicities of the supported immunoliposome were studied. Release results showed a minimum drug leakage in serum at body temperature from the particle. The release was initiated with a minor burst trigged by low pH inside the tumor cell and followed with a long term linear pattern. Cell assay results showed the highest binding affinity of the antibody or Herceptin® grafted nanoparticles to Her2 overexpressing cell lines and a lysosomal intracellular distribution of the endocytosised particles.
In the final study, a fabrication process for polymeric material nanoparticles was established. The process was capable of providing accurate control of the particle size with significant high output rates, thus largely extends the scope of materials for supporting the immunoliposome.Ph. D.
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Eschweiler, Zachary Taylor. "Superparamagnetic Nanoparticle TechnologyAn Analysis of Water, Water-treatment, Health-risks of Contaminated Water, and a Proposed Solution." Case Western Reserve University School of Graduate Studies / OhioLINK, 2017. http://rave.ohiolink.edu/etdc/view?acc_num=case1497012927923017.
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Bölükbaş, Deniz Ali [Verfasser], and Silke [Akademischer Betreuer] Meiners. "Development of novel nanoparticle-based therapeutics for treatment of lung cancer / Deniz Ali Bölükbaş ; Betreuer: Silke Meiners." München : Universitätsbibliothek der Ludwig-Maximilians-Universität, 2017. http://d-nb.info/1137466707/34.
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Moon, Taylor J. "Development of a Dual-Agonist Immunostimulatory Nanoparticle to Trigger Interferon β-Driven Anti-Tumor Immunity." Case Western Reserve University School of Graduate Studies / OhioLINK, 2020. http://rave.ohiolink.edu/etdc/view?acc_num=case1607349015331713.
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Gilliland, Stanley E. III. "Modified Seed Growth of Iron Oxide Nanoparticles in Benzyl Alcohol: Magnetic Nanoparticles for Radio Frequency Hyperthermia Treatment of Cancer." VCU Scholars Compass, 2014. http://scholarscompass.vcu.edu/etd/3611.
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Iron oxide nanoparticles have received sustained interest for biomedical applications as synthetic approaches are continually developed for precise control of nanoparticle properties. This thesis presents an investigation of parameters in the benzyl alcohol synthesis of iron oxide nanoparticles. A modified seed growth method was designed for obtaining optimal nanoparticle properties for magnetic fluid hyperthermia. With a one or two addition process, iron oxide nanoparticles were produced with crystallite sizes ranging from 5-20 nm using only benzyl alcohol and iron precursor. The effects of reaction environment, temperature, concentration, and modified seed growth parameters were investigated to obtain precise control over properties affecting radiofrequency heat generation. The reaction A2-24(205)_B2-24(205) produced monodispersed (PDI=0.265) nanoparticles with a crystallite size of 19.5±1.06 nm and the highest radiofrequency heating rate of 4.48 (°C/min)/mg (SAR=1,175.56 W/g, ILP=3.1127 nHm2/kg) for the reactions investigated. The benzyl alcohol modified seed growth method offers great potential for synthesizing iron oxide nanoparticles for radiofrequency hyperthermia.
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Guha, Ingrid F. "Effects of silica nanoparticle surface treatment and average diameter on the physical and mechanical properties of poly(dimethylsiloxane)-silica nanocomposites." Thesis, Massachusetts Institute of Technology, 2010. http://hdl.handle.net/1721.1/118564.
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Thesis: S.B., Massachusetts Institute of Technology, Department of Materials Science and Engineering, 2010.Cataloged from PDF version of thesis.
Includes bibliographical references (pages 35-37).
The purpose of this thesis was to quantify the effects of silica nanoparticle surface treatments and average silica nanoparticle diameter on various macroscopic properties of poly(dimethylsiloxane)-silica nanocomposites, specifically stiffness, wettability, and permeability to organic solvents. Poly(dimethylsiloxane)-silica nancomposites were prepared with constant amounts (4.8 wt%, 1.8 vol%) of fumed silica nanoparticles with varying surface treatments (hexamethyldisilazane and octamethylcyclotetrasiloxane) and varying particle diameter (7 and 12 nm). The Young's elastic modulus, mass increase due to dodecane absorption after 10 minutes, and advancing and receding water contact angles were measured for each nanocomposite. PDMS-silica nanocomposites containing untreated silica nanoparticles were found to have a higher Young's elastic modulus than nanocomposites containing hexamethyldisilazane-treated silica nanoparticles with the same diameter. However, nanocomposites containing identically sized silica nanoparticles with and without the octamethylcyclotetrasiloxane surface treatment had the same stiffness. The average nanocomposite stiffness increased slightly as the untreated silica nanoparticle diameter decreased from 12 nm to 7 nm. Varying the surface treatment or particle diameter of the filler did not significantly affect the level of dodecane absorption or the wettability of the nanocomposite. All nanocomposites showed approximately 20-23 wt% increase from dodecane absorption after 10 minutes of dodecane immersion. All nanocomposites exhibited average advancing contact angles around 115-120° and average receding contact angles around 85-90°. Nanocomposites were imaged using optical coherence tomography to examine particle dispersion. Potential differences in particle dispersion are discussed.
by Ingrid F. Guha.
S.B.
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Jones, Bernard Lee. "Development of dosimetry and imaging techniques for pre-clinical studies of gold nanoparticle-aided radiation therapy." Diss., Georgia Institute of Technology, 2011. http://hdl.handle.net/1853/43727.
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Cancer is one of the leading causes of death worldwide, and affects roughly 1.5 million new people in the United States every year. One of the leading tools in the detection and treatment of cancer is radiation. Tumors can be detected and identified using CT or PET scans, and can then be treated with external beam radiotherapy or brachytherapy. By taking advantage of the physical properties of gold and the biological properties of nanoparticles, gold nanoparticles (GNPs) can be used to improve both cancer radiotherapy and imaging. By infusing a tumor with GNPs, either using passive extravasation of nanoparticles by the tumor vasculature or active targeting of an antibody-conjugated nanoparticle to a specific tumor marker, the higher photon cross-section of gold will cause more radiation dose to be deposited in the tumor during photon-based radiotherapy. In principle, this would allow escalation of dose to the tumor while not increasing the dose to normal healthy tissue. Additionally, if a tumor infused with GNPs was irradiated by an external kilo-voltage source, the fluorescence emitted by the gold atoms would allow one to localize and quantify the GNP concentration. This work has two main aims: to quantify the GNP-mediated dose enhancement during GNRT on a nanometer scale, and to develop a refined imaging modality capable of quantifying GNP location and concentration within a small-animal-sized object. In order to quantify the GNP-mediated dose enhancement on a nanometer scale, a computational model was developed. This model combines both large-scale and small-scale calculations in order to accurately determine the heterogeneous dose distribution of GNPs. The secondary electron spectra were calculated using condensed history Monte Carlo, which is able to accurately take into account changes in beam quality throughout the tumor and calculate the average energy spectrum of the secondary charged particles created. Then, the dose distributions of these electron spectra were calculated on a nanometer scale using event-by-event Monte Carlo. The second aim is to develop an imaging system capable of reconstructing a tomographic image of GNP location and concentration in a small animal-sized object by capturing gold fluorescence photons emitted during irradiation of the object by an external beam. This would not only allow for localization of GNPs during gold nanoparticle-aided radiation therapy (GNRT), but also facilitate the use of GNPs as imaging agents for drug-delivery or other similar studies. The purpose of this study is to develop a cone-beam implementation of XFCT that meets realistic constrains on image resolution, detection limit, scan time, and dose. A Monte Carlo model of this imaging geometry was developed and used to test the methods of data acquisition and image reconstruction. The results of this study were then used to drive the production of a functioning benchtop, polychromatic cone-beam XFCT system.
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Verry, Camille. "Traitement des métastases cérébrales par radiothérapie et nanoparticule de gadolinium : du modèle pré clinique à l'utilisation chez l'homme Treatment of multiple brain metastases using gadolinium nanoparticles and radiotherapy: NANO-RAD, a phase 1 study protocol First in man injection of gadolinium-chelated based nanoparticle (AGuIX®) as theranostic agent for treatment of multiple brain metastases by adiotherapy: a case report." Thesis, Université Grenoble Alpes (ComUE), 2018. http://www.theses.fr/2018GREAS029.
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L'apparition de métastases cérébrales multiples est une évolution critique de nombreux cancers avec un impact majeur sur la survie globale. Une nouvelle nanoparticule à base de gadolinium, l’AGuIX®, a récemment démontré son efficacité en tant que radiosensibilisant et agent de contraste IRM dans plusieurs études précliniques. L’objectif de cette thèse est d’établir une preuve de concept sur un modèle animal puis de réaliser la première administration chez l’homme de ce nouveau médicament dans le cadre d’un essai de phase 1.La première partie de ce travail a consisté à l’irradiation en 6 MeV après injection d’AGuIX® d’un modèle de rat Fisher porteur du gliome cérébral 9L suivi par IRM. Nous avons mis en évidence une distribution favorable des nanoparticules dans la tumeur par effet EPR (Enhanced Permeability and Retention) avec une concentration de gadolinium dans la tumeur 20 fois plus importante que dans le cerveau sain. L’effet radiosensibilisant a été démontré avec une diminution significative (p=0.02) de la taille des tumeurs dans le groupe irradié après injection d’AGuIX®. Ces résultats, associés au profil de tolérance favorable sur les modèles animaux ont motivés le transfert chez l’homme de ce nouveau médicament dans une étude de phase 1 nommée NANO-RAD (EudraCT 2015-004259-30 ; NCT02820454). Il s’agit d’une étude monocentrique, ouverte, évaluant la faisabilité et la tolérance d'AGuIX® associé à une irradiation panencéphalique (30 Gy, 10 Fr de 3 Gy) pour des patients atteints de métastases cérébrales multiples. L'objectif principal est de déterminer la dose maximale tolérée des nanoparticules avec un schéma d’escalade de dose par palier de 3 patients à 15, 30, 50, 75 et 100 mg/kg. Les objectifs secondaires sont l’étude pharmacocinétique de la distribution d'AGuIX® par IRM, de la survie sans progression intracrânienne et de la survie globale. La première administration chez l’homme a été réalisée au CHU de Grenoble le 18 juillet 2016 et le dernier patient (n=15) a été inclus le 06 février 2018. L’ensemble des lésions, quelques soit l’origine histologique (poumon, mélanome, sein) ont eu une prise de contraste d’AGuIX® dont la concentration retrouvée dans la tumeur était proportionnelle à la dose injectée. La demi-vie sanguine moyenne est de 1h09 (± 26min). La tolérance au traitement a été bonne avec une escalade de dose jusqu’à 100 mg/kg qui devient ainsi la dose retenue pour la suite des essais cliniques. Sur les 14 patients évaluables, 12 ont eu un bénéfice clinique du traitement avec une diminution du volume tumoral. Les résultats préliminaires sont prometteurs en termes de tolérance, de distribution et d’efficacité et devront être confirmés par l’étude de phase 2 multicentrique randomisée prévue pour la fin de l’année 2018The occurrence of multiple brain metastases is a critical evolution of many cancers with a major impact on overall survival. A new gadolinium-based nanoparticle, AGuIX®, has recently demonstrated its efficacy as a radiosensitizer and MRI contrast agent in several preclinical studies. The objective of this thesis is to establish a proof of concept on an animal model and then to perform the first administration of this new drug in humans in a phase 1 trial. The first part of this work consisted of a 6 MeV irradiation after AGuIX® injection of a Fisher rat model carrying 9L cerebral gliomas assessed by MRI. A favorable distribution of nanoparticles was observed by EPR effect (Enhanced Permeability and Retention) with a concentration of gadolinium into the tumor 20 times higher than in healthy brain. The radiosensitizing effect was demonstrated with a significant decrease in tumor size (p=0.02) for the irradiated group with AGuIX® injection. These results, combined with the favorable safety profile in animal models, motivated the transfer of this new drug to humans in a Phase 1 study named NANO-RAD (EudraCT2015-004259-30; NCT02820454). This is a monocentric, open-label study evaluating the feasibility and safety of AGuIX® combined with whole brain radiation therapy (30 Gy, 10 Fr of 3 Gy) for patients with multiple brain metastases. The main objective is to determine the maximum tolerated dose of nanoparticles with a dose escalation scheme by steps of 3 patients at 15, 30, 50, 75 and 100 mg/kg. Secondary objectives are the pharmacokinetics, distribution of AGuIX® by MRI, intracranial progression-free survival and overall survival. The first human administration was performed at Grenoble University Hospital on 18 July 2016 and the last patient (n=15) was included on 06 February 2018. All metastases, whatever the histological type (lung, melanoma, breast) had a uptake of AGuIX® whose concentration in the tumor was proportional to the injected dose. The average blood half-life is 1h09 (± 26 min). Tolerance to the treatment was good with a dose escalation up to 100 mg/kg, which became the dose selected for further clinical trials. Of the 14 evaluable patients, 12 had a clinical benefit of treatment with a decrease in tumor volume. These preliminary results are promising in terms of safety, distribution and efficacy and should be confirmed by the randomized multicenter Phase 2 study planned for the end of 2018
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Le, Hoai Nga [Verfasser], Gianaurelio [Gutachter] Cuniberti, Michael [Gutachter] Stintz, and Sven [Gutachter] Wießner. "A concept for nanoparticle-based photocatalytic treatment of wastewater from textile industry / Hoai Nga Le ; Gutachter: Gianaurelio Cuniberti, Michael Stintz, Sven Wießner." Dresden : Saechsische Landesbibliothek- Staats- und Universitaetsbibliothek Dresden, 2018. http://d-nb.info/1226430562/34.
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Hood, Robert L. "Development of a Fiberoptic Microneedle Device for Simultaneous Co-Delivery of Fluid Agents and Laser Light with Specific Applications in the Treatment of Brain and Bladder Cancers." Diss., Virginia Tech, 2013. http://hdl.handle.net/10919/51678.
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This dissertation describes the development of the fiberoptic microneedle device (FMD), a microneedle technology platform for fluid and light delivery, from general engineering characterization to specific applications in treating bladder and brain cancers. The central concept of the FMD is physical modification of silica fiberoptics and capillary tubes into sharp microneedles capable of penetrating a tissue's surface, enabling light and fluid delivery into the interstitial spaces. Initial studies sought to characterize the mechanical penetration and optical delivery of multimode fiberoptics and capillary tubes modified through a custom, CO2 laser melt-drawing technique. Additional work with multimode fibers investigated using an elastomeric lateral support medium to ensure robust penetration of small diameter fibers. These early experiments laid an engineering foundation for understanding the FMD technology.
Subsequent studies focused on developing the FMD to treat specific diseases. The first such investigation sought to leverage the high aspect ratio nature of FMDs made from long capillary tubes as a therapy delivery device deployable through the instrument channel of a urological cystoscope. The therapeutic strategy was to infuse single-walled carbon nanohorns (SWNHs), a carbon-based nanoparticle allowing surface modification and drug encapsulation, into the infiltrating front of later stage bladder tumors. The SWNHs primarily serve as exogenous chromophores, enabling a fluid-based control of photothermal heat generation created when the SWNHs interacted with laser energy from an interstitial FMD or a light-emitting fiber in the bladder's interior. The study described here primarily sought to characterize the dispersal of the infused SWNHs and the photothermal response of the particles when heated with a 1064 nm laser.
The FMD was also developed as a platform capable of conducting convection-enhanced delivery (CED), a therapeutic approach to treat invasive tumors of the central nervous system such as malignant glioma (MG). Intracranial CED involves the placement of small catheters local to the tumor site and slow infusion of a chemotherapeutic over long timeframes (12-72 hours). A primary challenge of this treatment approach is infused chemotherapeutics not dispersing sufficiently to reach the infiltrating cells in the tumor's margins. The hypothetical improvement provided by the FMD technology is using sub-lethal photothermal heating to sufficiently increase the diffusive and convective transport of an infusate to reach infiltrative cells in the tumor's periphery. Initial experiments sought to demonstrate and characterize a heat-mediated increase of volumetric dispersal in Agarose tissue phantoms and ex vivo tissue. Subsequent studies with in vivo rodent models determined the best laser parameters to achieve the desired levels of diffuse, sub-lethal heat generation and then demonstrated the hypothesis of increasing the rate of volumetric dispersal though concurrent local hyperthermia. This research was the first demonstration of photothermal augmentation of an interstitially infused fluid's dispersal rate, which may have uses outside of the CED approach to brain cancer exhibited here. Taken in sum, this manuscript describes the potency and versatility of the FMD technology platform through its development in various biomedical applications.Ph. D.
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Morgan, Dana Lee. "Alkaline hydrothermal treatment of titanate nanostructures." Thesis, Queensland University of Technology, 2010. https://eprints.qut.edu.au/39298/1/Dana_Morgan_Thesis.pdf.
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Since its initial proposal in 1998, alkaline hydrothermal processing has rapidly become an established technology for the production of titanate nanostructures. This simple, highly reproducible process has gained a strong research following since its conception. However, complete understanding and elucidation of nanostructure phase and formation have not yet been achieved. Without fully understanding phase, formation, and other important competing effects of the synthesis parameters on the final structure, the maximum potential of these nanostructures cannot be obtained. Therefore this study examined the influence of synthesis parameters on the formation of titanate nanostructures produced by alkaline hydrothermal treatment. The parameters included alkaline concentration, hydrothermal temperature, the precursor material‘s crystallite size and also the phase of the titanium dioxide precursor (TiO2, or titania). The nanostructure‘s phase and morphology was analysed using X-ray diffraction (XRD), Raman spectroscopy and transmission electron microscopy. X-ray photoelectron spectroscopy (XPS), dynamic light scattering (non-invasive backscattering), nitrogen sorption, and Rietveld analysis were used to determine phase, for particle sizing, surface area determinations, and establishing phase concentrations, respectively. This project rigorously examined the effect of alkaline concentration and hydrothermal temperature on three commercially sourced and two self-prepared TiO2 powders. These precursors consisted of both pure- or mixed-phase anatase and rutile polymorphs, and were selected to cover a range of phase concentrations and crystallite sizes. Typically, these precursors were treated with 5–10 M sodium hydroxide (NaOH) solutions at temperatures between 100–220 °C. Both nanotube and nanoribbon morphologies could be produced depending on the combination of these hydrothermal conditions. Both titania and titanate phases are comprised of TiO6 units which are assembled in different combinations. The arrangement of these atoms affects the binding energy between the Ti–O bonds. Raman spectroscopy and XPS were therefore employed in a preliminary study of phase determination for these materials. The change in binding energy from a titania to a titanate binding energy was investigated in this study, and the transformation of titania precursor into nanotubes and titanate nanoribbons was directly observed by these methods. Evaluation of the Raman and XPS results indicated a strengthening in the binding energies of both the Ti (2p3/2) and O (1s) bands which correlated to an increase in strength and decrease in resolution of the characteristic nanotube doublet observed between 320 and 220 cm.1 in the Raman spectra of these products. The effect of phase and crystallite size on nanotube formation was examined over a series of temperatures (100.200 �‹C in 20 �‹C increments) at a set alkaline concentration (7.5 M NaOH). These parameters were investigated by employing both pure- and mixed- phase precursors of anatase and rutile. This study indicated that both the crystallite size and phase affect nanotube formation, with rutile requiring a greater driving force (essentially �\harsher. hydrothermal conditions) than anatase to form nanotubes, where larger crystallites forms of the precursor also appeared to impede nanotube formation slightly. These parameters were further examined in later studies. The influence of alkaline concentration and hydrothermal temperature were systematically examined for the transformation of Degussa P25 into nanotubes and nanoribbons, and exact conditions for nanostructure synthesis were determined. Correlation of these data sets resulted in the construction of a morphological phase diagram, which is an effective reference for nanostructure formation. This morphological phase diagram effectively provides a .recipe book�e for the formation of titanate nanostructures. Morphological phase diagrams were also constructed for larger, near phase-pure anatase and rutile precursors, to further investigate the influence of hydrothermal reaction parameters on the formation of titanate nanotubes and nanoribbons. The effects of alkaline concentration, hydrothermal temperature, crystallite phase and size are observed when the three morphological phase diagrams are compared. Through the analysis of these results it was determined that alkaline concentration and hydrothermal temperature affect nanotube and nanoribbon formation independently through a complex relationship, where nanotubes are primarily affected by temperature, whilst nanoribbons are strongly influenced by alkaline concentration. Crystallite size and phase also affected the nanostructure formation. Smaller precursor crystallites formed nanostructures at reduced hydrothermal temperature, and rutile displayed a slower rate of precursor consumption compared to anatase, with incomplete conversion observed for most hydrothermal conditions. The incomplete conversion of rutile into nanotubes was examined in detail in the final study. This study selectively examined the kinetics of precursor dissolution in order to understand why rutile incompletely converted. This was achieved by selecting a single hydrothermal condition (9 M NaOH, 160 °C) where nanotubes are known to form from both anatase and rutile, where the synthesis was quenched after 2, 4, 8, 16 and 32 hours. The influence of precursor phase on nanostructure formation was explicitly determined to be due to different dissolution kinetics; where anatase exhibited zero-order dissolution and rutile second-order. This difference in kinetic order cannot be simply explained by the variation in crystallite size, as the inherent surface areas of the two precursors were determined to have first-order relationships with time. Therefore, the crystallite size (and inherent surface area) does not affect the overall kinetic order of dissolution; rather, it determines the rate of reaction. Finally, nanostructure formation was found to be controlled by the availability of dissolved titanium (Ti4+) species in solution, which is mediated by the dissolution kinetics of the precursor.
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Hasan, Mohammad Nazmul. "Developing Glycopeptide based nanocarriers by ring opening polymerization for drug delivery applications." Thesis, Uppsala universitet, Institutionen för kemi - Ångström, 2014. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-233891.
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Synthetic glycopeptides have attracted much interest in the biomedical field due to their structural similarities to the natural glycopeptides or glycoproteins. It is still difficult to synthesize glycopeptides with greater efficiency and ring opening polymerization remains an effective way to do so. Proteoglycans are a special class of glycoproteins with glycosaminoglycan chains. In this study, I tried to do controlled ring opening polymerization of Hyaluronic acid derivatives with smaller to higher molecular weight while avoiding side reactions. It is challenging to work with higher molecular weight molecules and do a click reaction in water effectively. Making nanopolymers with a desired size, studies of the characteristics, and how to build nanocarriers for drug delivery application was the focus of this work. Polymeric characteristics, e.g., modification and polymer formation were studied by nuclear magnetic resonance technique; Particle size was studied by dynamic light scattering and the loading of rhodamine B encapsulated into the polymer was measured by confocal imaging technique.
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Wilcox, Ashley M. "Silver Nanoparticles: An effective antibacterial agent against Gram-negative bacteria." Wright State University / OhioLINK, 2019. http://rave.ohiolink.edu/etdc/view?acc_num=wright1576621225597745.
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Ouvinha, De Oliveira Rachel. "Development and evaluation of nanoparticles for cancer treatment." Thesis, Paris 11, 2014. http://www.theses.fr/2014PA114808/document.
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Cette thèse concerne le développement et l'évaluation des nanoparticules pour le traitement du cancer et plus particulièrement pour le cancer de la prostate.Le manuscrit comprend une revue de la littérature sur l'application de la nano médecine pour le traitement du cancer de la prostate. Dans la première partie expérimentale, des nanoparticules d'or fonctionnalisées ont été caractérisées et chargées avec le docétaxel par adsorption non covalente.Ces nanoparticules d'or ont montré un effet cytotoxique in vitro prolongé contre les cellules cancéreuses de la prostate. La deuxième partie expérimentale de cette thèse décrit une étude de synthèse et une nano-précipitation de polyesters pour la co-délivrance de deux médicaments chimio-thérapeutiques, le docétaxel (DOC) et la mitoxantrone (MIT). Les polycaprolactone, poly(acide lactique) et poly(lactide-co-glycolide) ont été synthétisés par polymérisation par ouverture de cycle avec des poids moléculaires différents de polyéthylène glycol. Des nanoparticules monodisperses d’un diamètre d’environ 80 nm ont été obtenues et se sont avérées être efficaces contre les cellules cancéreuses de la prostate quand cela est chargé en MIT et DOC. De plus, un effet synergique a été observé en utilisant des combinaisons de ces nanoparticules. Par conséquent, ces nanoparticules, à base de polyester, ont de potentielles applications cliniquesThis thesis concerns the development and evaluation of nanoparticles for cancer treatment, and in particular to prostate cancer. The manuscript includes a literature review on the application of nanomedicine to the treatment of prostate cancer. In the first experimental part, functionalized gold nanoparticles were characterized and loaded with docetaxel by non covalent adsorption. These gold nanoparticles showed a sustained cytotoxic effect in vitro against prostate cancer cells. The second experimental part of this thesis describes a study of synthesis and nanoprecipitation of polyesters for the co-delivery of two chemotherapeutic drugs, docetaxel (DOC) and mitoxantrone (MIT). Polycaprolactone, poly(lactic acid) and poly (lactide-co-glycolide) were synthesized by ring-opening polymerization with different molecular weights of polyethylene glycol. Monodisperse nanoparticles with diameters of less than 80 nm were produced and were shown to be effective against prostate cancer cells when loaded with MIT and DOC. Moreover, a synergistic effect was observed using combinations of these nanoparticles. Therefore, these polyester based nanoparticles have potential clinical applications
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Franke, Christina E. "Tobacco Mosaic Virus Nanocarrier for Restored Cisplatin Efficacy in Platinum-Resistant Ovarian Cancer." Case Western Reserve University School of Graduate Studies / OhioLINK, 2017. http://rave.ohiolink.edu/etdc/view?acc_num=case1493810190306879.
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Barton, Lauren Elizabeth. "Fate and Transformation of Metal-(Oxide) Nanoparticles in Wastewater Treatment." Diss., Aix-Marseille, 2014. http://hdl.handle.net/10161/8661.
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The study and application of materials possessing size dimensions in the nano scale range and, as a result, unique properties have led to the birth of a new field; nanotechnology. Scientists and engineers have discovered and are exploiting the novel physicochemical characteristics of nanoparticles (NPs) to enhance consumer products and technologies in ways superior to their bulk counterparts. Escalating production and use of NPs will unavoidably lead to release and exposure to environmental systems. This introduction of emerging potential contaminant NPs will provide new and interesting challenges for exposure and risk forecasting as well as environmental endurance.
The ultimate goal of this research is to develop a framework that incorporates experimental and computational efforts to assess and better understand the exposure of metal and metal-oxide NPs released to wastewater treatment plants (WWTPs) and further implications on land application units (LAUs) where biosolids can be applied. The foundation of the computational effort is comprised of Monte Carlo mass balance models that account for the unique processes affecting NP fate and transport through the different technical compartments of a WWTP and LAU. Functional assay and bioreactor experiments in environmental media were used to determine parameters capable of describing the critical processes that impact the fate of NPs in wastewater.
The results of this research indicate that a simplified, but still environmentally relevant nano-specific exposure assessment is possible through experimentation to parameterize adapted models. Black box modeling efforts, which have been shown in previous studies, show no disadvantage relative to discretization of technical compartments as long as all key transport and fate mechanisms are considered. The distribution coefficient (_), an experimentally determined, time-dependent parameter, can be used to predict the distribution of NPs between the liquid and solid phase in WWTPs. In addition, this parameter can be utilized a step further for the estimation of the more fundamental, time independent attachment efficiency between the NPs and the solids in wastewater. The NP core, size, and surface coating will influence the value of these parameters in addition to the background particle characteristics as the parameters are specific to the environmental system of study. For the metal and metal-oxide NPs studied, preferential overall association of approximately 90% or greater with the solid phase of wastewater was observed and predicted.
Furthermore, NP transformations including dissolution, redox reactions, and adsorption can potentially impact exposure. For example, experimental results showed that nano-CeO2 is reduced from Ce(IV) to Ce(III) when in contact with wastewater bacteria where Ce2S3 will likely govern the Ce(III) phase in biosolids. From the literature, similar transformations have been observed with Ag and ZnO NPs to Ag2S and ZnS. With respect to TiO2 NPs, studies indicated that due to high insolubility, these NPs would not undergo transformation in WWTPs. The distribution and transformation rate coefficients can then be used in fate models to predict the NP species exposed to aquatic and terrestrial systems and environmentally relevant concentrations released from WWTPs.
Upon completion of the WWTP model, the predicted concentrations of NPs and NP transformation byproducts released in effluent and biosolids were attainable. A simple mass balance model for NP fate in LAUs was then developed to use this output. Results indicate that NP loading on LAUs would be very low but that build up over time to steady state could result in mass concentrations on the order of the typical level for the background metal in soil. Transport processes of plant uptake and leaching were expected to greatly impact the solid phase concentration of the NPs remaining in the LAU, while rainfall did not impart a significant influence upon variation between low and high annual amounts. The significance of this research is the introduction of a method for NP exposure assessment in WWTPs and subsequently in LAUs. This work describes and quantifies the key processes that will impact Ag, TiO2, CeO2 and ZnO NP fate and transport, which can inform future studies, the modeling community and regulatory agencies.
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Fallon, Marissa S. "Drug overdose treatment by nanoparticles." [Gainesville, Fla.] : University of Florida, 2005. http://purl.fcla.edu/fcla/etd/UFE0013055.
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Ebeid, Kareem Atef Nassar. "Nanoparticles for targeted treatment of cancer." Diss., University of Iowa, 2018. https://ir.uiowa.edu/etd/6567.
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Cancer is the second leading cause of death in the USA, following cardiovascular disease. Treating cancer using conventional therapies is associated with low response rates and high toxicity, because these therapies usually lack specific tumor accumulation. Loading anticancer drugs into intelligently designed polymeric nanoparticles (NPs) can serve in delivering these drugs specifically to the tumor site, thus boosting their efficacy and reducing any associated off target toxicity. Targeting NPs to the tumor site can occur through either passive or active means. In passive targeting, NPs of specific size and surface characteristics can exploit the tumor’s erratic vasculature and occluded lymphatic drainage to extravasate the systemic circulation and accumulate preferentially at the tumor site. Active targeting mandates grafting the surface of NPs with a ligand that specifically interacts with a protein expressed at higher levels at the tumor site, in comparison to elsewhere in the body. In the current research, we independently investigated the utilization of passive and active targeting strategies to treat aggressive forms of cancer.
Initially, passively targeted poly(lactic-co-glycolic acid) (PLGA) NPs to treat aggressive forms of endometrial cancer (EC) were investigated. A novel combination of soluble paclitaxel (PTX), a first line chemotherapy for EC, and soluble BIBF1120 (BIBF, nintedanib), an antiangiogenic molecular inhibitor, was first tested against three EC cell lines bearing different p53 mutations. The results showed that only EC cells with loss of function (LOF) p53 were sensitive to the combination therapy, indicating the potential of this combination to engender synthetic lethality to PTX. Next, NPs loaded with PTX were investigated with respect to the impact of varying the polymer lactic acid to glycolic acid ratio and the surfactant type on the major physicochemical properties of the prepared nanoparticles, drug loading, cellular uptake, cytotoxicity, and drug release. The optimum formulation was then loaded with BIBF and the combination of independently loaded passively targeted NPs were further evaluated for in vivo activity against a xenograft model of LOF p53 EC. The combination of independently loaded NPs exhibited the highest reduction in tumor volume and prolonged survival when compared to soluble PTX, PTX NPs or untreated control. These data highlight this specific combination of NPs as a novel promising therapy for LOF p53 EC.
In a second study, the use of actively targeted NPs to treat liver cancer was explored. In this study, a combination of small interfering RNA (siRNA) against astrocyte elevated gene-1 (AEG-1), and all-trans retinoic acid (ATRA) was investigated as a new therapy for hepatocellular carcinoma (HCC). AEG-1 is a highly expressed oncogene that is directly involved in HCC progression and aggressiveness, in addition to reducing the ability of retinoic acid to induce apoptosis in HCC cells. First, a new conjugate was synthesized that was capable of delivering siRNA selectively to HCC cells, using galactose as a targeting moiety. The conjugate was prepared by linking poly(amidoamine) (PAMAM) dendrimers, polyethylene glycol (PEG) and lactobionic acid (Gal, disaccharide containing galactose) (PAMAM-PEG-Gal). We confirmed the synthesis of the conjugate using 1H-NMR, Mass spectrometry and Matrix-Assisted Laser Desorption/Ionization (MALDI) Mass Spectrometry. Next, nanoplexes of the synthesized conjugate, PAMAM-PEG-Gal, and AEG-1 siRNA were prepared. Nanoplexes were further characterized for their size, surface charge, morphology, and electrophoretic mobility to identify the optimum complexation ratio between PAMAM-PEG-Gal and the siRNA. Then, mice bearing orthotopic luciferase expressing HCC cells were treated with the optimum nanoplex formulation. Results showed that a combination of AEG-1 nanoplexes and ATRA results in a significant reduction in luciferase expression, reduced liver weight, lower AEG-1 mRNA levels and increased apoptosis, when compared to utilizing nanoplexes with silencing control (siCon), siCon+ATRA, or AEG-1 nanoplexes alone. The results indicate that the combination of liver-targeted AEG-1 nanoplexes and ATRA may be a potential treatment for aggressive HCC.
These data place targeted NPs as a promising efficient delivery system for cancer treatment.
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Jain, Rohan. "Biogenic nanoparticles of elemental selenium : synthesis, characterization and relevance in wastewater treatment." Thesis, Paris Est, 2014. http://www.theses.fr/2014PEST1178/document.
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Les nanoparticules exposent beaucoup de propriétés uniques en comparaison de la possession de matériels (matières) en gros (vrac) à leur haute surface au ratio de volume. Des nanoparticules de sélénium élémentaires exposent aussi les nouvelles propriétés qui sont exploitées dans la formation de cellules solaires, des redresseurs de semi-conducteur et le déplacement (déménagement) de mercure et le cuivre. Cependant, la synthèse chimique de nanoparticules de sélénium élémentaires est coûteuse, exige des équipements spécialisés et utilise des produits chimiques toxiques. D'autre part, la production biologique de nanoparticules de sélénium élémentaires (BioSeNPs) peut être un remplacement(remplaçant) vert pour les chimiquement produits. BioSeNPs sont produit par la réduction microbienne de sélénite et selenate. La source du sélénium oxyanions peut être le wastewaters, où la réduction microbienne est employée comme une technologie de remédiation pour le déplacement (déménagement) de sélénium (...)Nanoparticles exhibit many unique properties as compared to the bulk materials owning to their high surface to volume ratio. Elemental selenium nanoparticles also exhibit novel properties that are exploited in formation of solar cells, semiconductor rectifiers and removal of mercury and copper. However, the chemical synthesis of elemental selenium nanoparticles is costly, requires specialized equipments and uses toxic chemicals. On the other hand, biological production of elemental selenium nanoparticles (BioSeNPs) can be a green replacement for the chemically produced ones.BioSeNPs are produced by microbial reduction of selenite and selenate. The source of the selenium oxyanions can be the wastewaters, where microbial reduction is employed as a remediation technology for the removal of selenium. The formed BioSeNPs are colloidal poly-disperse particles with negative surface charge and are present in the effluent of the microbial reactor. However, the properties of these BioSeNPs are not very well understood. This knowledge would help us to produce better quality selenium nanomaterials, exploit produced BioSeNPs in the wastewater treatment and control the fate of these BioSeNPs in the microbial reactors. The characterization of BioSeNPs revealed the presence of the extracellular polymeric substances (EPS) on the surface of BioSeNPs. The EPS was identified to control the surface charge and to some extent the shape of the BioSeNPs. It was also found that the microbial reduction at 55 and 65 °C can lead to the formation of selenium nanowires as compared to nanospheres when the reduction takes place at 30 °C. These selenium nanowires are present in trigonal crystalline structure and are colloidal suspension, unlike the chemically formed trigonal selenium nanorods. This colloidal nature is due to negative ζ-potential values owning to the presence of EPS on the surface of biogenic selenium nanowires. Since proteins are a major component present in the EPS, the presence of various proteins on the surface of BioSeNPs was determined. The interaction of the various amino acids with the BioSeNPs was also evaluated.The interaction of heavy metals and BioSeNPs was studied with a view of developing a technology where BioSeNPs present in the effluent of an upflow anaerobic sludge blanket (UASB) reactor are mixed with heavy metals containing wastewater leading to removal of both BioSeNPs and heavy metals. It was found that Cu, Cd and Zn can be effectively adsorbed onto BioSeNPs. Cu was 4.7 times preferentially adsorbed onto BioSeNPs. The interaction of BioSeNPs with the heavy metals led to less negative ζ-potential of BioSeNPs loaded with heavy metals and thus better settling of BioSeNPs was achieved. The presence of BioSeNPs in the effluent of the microbial reactor treating selenium oxyanions containing wastewaters is undesirable due to higher total selenium concentrations. Thus, the attempts to capture of these BioSeNPs in the biomass/bioreactors were made. The activated sludge reactor system was investigated to aerobically reduce selenite to BioSeNPs and trap them in the activated sludge flocs. Around 80% of the fed selenium was trapped in the biomass. Sequential extraction revealed that the trapped selenium is BioSeNPs. The trapping of BioSeNPs in the sludge improved the settleability and hydrophilicity of the activated sludge flocs. When the UASB reactor were operated under mesophilic and thermophilic conditions, the total selenium concentration in the effluent under thermophilic conditions were lower than that of observed in mesophilic conditions suggesting better trapping of BioSeNPs.Keywords: Selenium, bioreduction, BioSeNPs, EPS, ζ-potential, heavy metals, activated sludge, UASB reactors, thermophilic