Journal articles: 'Cellular Delivery - Anionic Nanoparticles'

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Maity, Amit Ranjan, and Nikhil R. Jana. "Chitosan−Cholesterol-Based Cellular Delivery of Anionic Nanoparticles." Journal of Physical Chemistry C 115, no. 1 (December 14, 2010): 137–44. http://dx.doi.org/10.1021/jp108828c.

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Xu, Zhi Ping, and G. Q. (Max) Lu. "Layered double hydroxide nanomaterials as potential cellular drug delivery agents." Pure and Applied Chemistry 78, no. 9 (January 1, 2006): 1771–79. http://dx.doi.org/10.1351/pac200678091771.

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This paper briefly reviews the recent progress in using layered double hydroxide (LDH) nanomaterials as cellular delivery agents. The advantages of LDHs as cellular delivery agents are summarized, and the processes of interaction/de-intercalation of anionic drugs (genes) into/from LDH nanoparticles are discussed. Then the cellular delivery of LDH-drug (gene) nanohybrids and subsequent intracellular processes are presumably proposed. At the end, some challenges and remarks for efficient delivery of drugs (genes) via LDH nanoparticles are provided to the best of our knowledge.

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Choi, Soo-Jin, Jae-Min Oh, Taeun Park, and Jin-Ho Choy. "Cellular Toxicity of Inorganic Hydroxide Nanoparticles." Journal of Nanoscience and Nanotechnology 7, no. 11 (November 1, 2007): 4017–20. http://dx.doi.org/10.1166/jnn.2007.085.

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Layered double hydroxides (LDHs), anionic clays, have attracted increasing interest as nanovehicles for delivering genes, drugs, and bio-active molecules into cells. However, no attempts have been made to evaluate the potential undesirable effects of LDH nanoparticles. The cytotoxicity of LDHs with different chemical compositions (ZnAl- and MgAl-LDH) was systematically evaluated in various cell types, such as human normal cells, carcinoma cells, and red blood cells, by measuring cell viability, cell proliferation, membrane damage, and hemolytic effect. No significant cytotoxic effects could be seen in both cases, but ZnAl-LDH was determined to be slightly more toxic than MgAl-LDH in terms of membrane damage and hemolysis induction. It is, therefore, expected that LDHs could be promising candidates for novel inorganic drug delivery carriers.

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Choi, Soo-Jin, Jae-Min Oh, Taeun Park, and Jin-Ho Choy. "Cellular Toxicity of Inorganic Hydroxide Nanoparticles." Journal of Nanoscience and Nanotechnology 7, no. 11 (November 1, 2007): 4017–20. http://dx.doi.org/10.1166/jnn.2007.18081.

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Layered double hydroxides (LDHs), anionic clays, have attracted increasing interest as nanovehicles for delivering genes, drugs, and bio-active molecules into cells. However, no attempts have been made to evaluate the potential undesirable effects of LDH nanoparticles. The cytotoxicity of LDHs with different chemical compositions (ZnAl- and MgAl-LDH) was systematically evaluated in various cell types, such as human normal cells, carcinoma cells, and red blood cells, by measuring cell viability, cell proliferation, membrane damage, and hemolytic effect. No significant cytotoxic effects could be seen in both cases, but ZnAl-LDH was determined to be slightly more toxic than MgAl-LDH in terms of membrane damage and hemolysis induction. It is, therefore, expected that LDHs could be promising candidates for novel inorganic drug delivery carriers.

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Berger, Eric, Dalibor Breznan, Sandra Stals, Viraj J. Jasinghe, David Gonçalves, Denis Girard, Sylvie Faucher, Renaud Vincent, Alain R. Thierry, and Carole Lavigne. "Cytotoxicity assessment, inflammatory properties, and cellular uptake of Neutraplex lipid-based nanoparticles in THP-1 monocyte-derived macrophages." Nanobiomedicine 4 (January 1, 2017): 184954351774625. http://dx.doi.org/10.1177/1849543517746259.

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Current antiretroviral drugs used to prevent or treat human immunodeficiency virus type 1 (HIV-1) infection are not able to eliminate the virus within tissues or cells where HIV establishes reservoirs. Hence, there is an urgent need to develop targeted delivery systems to enhance drug concentrations in these viral sanctuary sites. Macrophages are key players in HIV infection and contribute significantly to the cellular reservoirs of HIV because the virus can survive for prolonged periods in these cells. In the present work, we investigated the potential of the lipid-based Neutraplex nanosystem to deliver anti-HIV therapeutics in human macrophages using the human monocyte/macrophage cell line THP-1. Neutraplex nanoparticles as well as cationic and anionic Neutraplex nanolipoplexes (Neutraplex/small interfering RNA) were prepared and characterized by dynamic light scattering. Neutraplex nanoparticles showed low cytotoxicity in CellTiter-Blue reduction and lactate dehydrogenase release assays and were not found to have pro-inflammatory effects. In addition, confocal studies showed that the Neutraplex nanoparticles and nanolipoplexes are rapidly internalized into THP-1 macrophages and that they can escape the late endosome/lysosome compartment allowing the delivery of small interfering RNAs in the cytoplasm. Furthermore, HIV replication was inhibited in the in vitro TZM-bl infectivity assay when small interfering RNAs targeting CXCR4 co-receptor was delivered by Neutraplex nanoparticles compared to a random small interfering RNA sequence. This study demonstrates that the Neutraplex nanosystem has potential for further development as a delivery strategy to efficiently and safely enhance the transport of therapeutic molecules into human monocyte-derived macrophages in the aim of targeting HIV-1 in this cellular reservoir.

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Tsai, Li-Hui, Chia-Hsiang Yen, Hao-Ying Hsieh, and Tai-Horng Young. "Doxorubicin Loaded PLGA Nanoparticle with Cationic/Anionic Polyelectrolyte Decoration: Characterization, and Its Therapeutic Potency." Polymers 13, no. 5 (February 25, 2021): 693. http://dx.doi.org/10.3390/polym13050693.

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Optimized Doxorubicin hydrochloride (DOX) loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles (DPN) were prepared by controlling the water/oil distribution of DOX at different pH solutions and controlling the electrostatic interaction between DOX and different terminated-end PLGAs. Furthermore, cationic polyethylenimine (PEI) and anionic poly (acrylic acid) (PAA) were alternately deposited on DPN surface to form PEI-DPN (IDPN) and PAA-PEI-DPN (AIDPN) to enhance cancer therapy potency. Compared to DPN, IDPN exhibited a slower release rate in physiological conditions but PEI was demonstrated to increase the efficiency of cellular uptake and endo/lysosomal escape ability. AIDPN, with the outermost negatively charged PAA layer, still retained better endo/lysosomal escape ability compared to DPN. In addition, AIDPN exhibited the best pH-dependent release profile with 1.6 times higher drug release in pH 5.5 than in pH 7.4. Therefore, AIDPN with the characteristics of PEI and PAA simultaneously was the most optional cancer therapy choice within these three PLGA nanoparticles. As the proposed nanoparticles integrated optimal procedure factors, and possessed cationic and anionic outlayer, our drug delivery nanoparticles can provide an alternative solution to current drug delivery technologies.

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Rotan, Olga, Katharina N. Severin, Simon Pöpsel, Alexander Peetsch, Melisa Merdanovic, Michael Ehrmann, and Matthias Epple. "Uptake of the proteins HTRA1 and HTRA2 by cells mediated by calcium phosphate nanoparticles." Beilstein Journal of Nanotechnology 8 (February 7, 2017): 381–93. http://dx.doi.org/10.3762/bjnano.8.40.

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The efficient intracellular delivery of (bio)molecules into living cells remains a challenge in biomedicine. Many biomolecules and synthetic drugs are not able to cross the cell membrane, which is a problem if an intracellular mode of action is desired, for example, with a nuclear receptor. Calcium phosphate nanoparticles can serve as carriers for small and large biomolecules as well as for synthetic compounds. The nanoparticles were prepared and colloidally stabilized with either polyethyleneimine (PEI; cationic nanoparticles) or carboxymethyl cellulose (CMC; anionic nanoparticles) and loaded with defined amounts of the fluorescently labelled proteins HTRA1, HTRA2, and BSA. The nanoparticles were purified by ultracentrifugation and characterized by dynamic light scattering and scanning electron microscopy. Various cell types (HeLa, MG-63, THP-1, and hMSC) were incubated with fluorescently labelled proteins alone or with protein-loaded cationic and anionic nanoparticles. The cellular uptake was followed by light and fluorescence microscopy, confocal laser scanning microscopy (CLSM), and flow cytometry. All proteins were readily transported into the cells by cationic calcium phosphate nanoparticles. Notably, only HTRA1 was able to penetrate the cell membrane of MG-63 cells in dissolved form. However, the application of endocytosis inhibitors revealed that the uptake pathway was different for dissolved HTRA1 and HTRA1-loaded nanoparticles.

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Uto, Tomofumi, Takami Akagi, Mitsuru Akashi, and Masanori Baba. "Induction of Potent Adaptive Immunity by the Novel Polyion Complex Nanoparticles." Clinical and Vaccine Immunology 22, no. 5 (March 25, 2015): 578–85. http://dx.doi.org/10.1128/cvi.00080-15.

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ABSTRACTThe development of effective and simple methods of vaccine preparation is desired for the prophylaxis and treatment of a variety of infectious diseases and cancers. We have created novel polyion complex (PIC) nanoparticles (NPs) composed of amphiphilic anionic biodegradable poly(γ-glutamic acid) (γ-PGA) and cationic polymers as a vaccine adjuvant. PIC NPs can be prepared by mixing γ-PGA-graft-l-phenylalanine ethylester (γ-PGA-Phe) polymer with cationic polymer in phosphate-buffered saline. We examined the efficacy of PIC NPs for antigen delivery and immunostimulatory activityin vitroandin vivo. PIC NPs enhanced the uptake of ovalbumin (OVA) by dendritic cells (DCs) and subsequently induced DC maturation. The immunization of mice with OVA-carrying PIC NPs induced potent and antigen-specific cellular and humoral immunity. Since PIC NPs can be created with water-soluble anionic γ-PGA-Phe and a cationic polymer by simple mixing in the absence of any organic solvents, PIC NPs may have potential as a novel candidate for an effective antigen carrier and vaccine adjuvant.

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Cotta, Karishma Berta, Sarika Mehra, and Rajdip Bandyopadhyaya. "pH-driven enhancement of anti-tubercular drug loading on iron oxide nanoparticles for drug delivery in macrophages." Beilstein Journal of Nanotechnology 12 (October 7, 2021): 1127–39. http://dx.doi.org/10.3762/bjnano.12.84.

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Nanoparticle deployment in drug delivery is contingent upon controlled drug loading and a desired release profile, with simultaneous biocompatibility and cellular targeting. Iron oxide nanoparticles (IONPs), being biocompatible, are used as drug carriers. However, to prevent aggregation of bare IONPs, they are coated with stabilizing agents. We hypothesize that, zwitterionic drugs like norfloxacin (NOR, a fluoroquinolone) can manifest dual functionality – nanoparticle stabilization and antibiotic activity, eliminating the need of a separate stabilizing agent. Since these drugs have different charges, depending on the surrounding pH, drug loading enhancement could be pH dependent. Hence, upon synthesizing IONPs, they were coated with NOR, either at pH 5 (predominantly as cationic, NOR+) or at pH 10 (predominantly as anionic, NOR−). We observed that, drug loading at pH 5 exceeded that at pH 10 by 4.7–5.7 times. Furthermore, only the former (pH 5 system) exhibited a desirable slower drug release profile, compared to the free drug. NOR-coated IONPs also enable a 22 times higher drug accumulation in macrophages, compared to identical extracellular concentrations of the free drug. Thus, lowering the drug coating pH to 5 imparts multiple benefits – improved IONP stability, enhanced drug coating, higher drug uptake in macrophages at reduced toxicity and slower drug release.

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Tukova, Anastasiia, Inga Christine Kuschnerus, Alfonso Garcia-Bennett, Yuling Wang, and Alison Rodger. "Gold Nanostars with Reduced Fouling Facilitate Small Molecule Detection in the Presence of Protein." Nanomaterials 11, no. 10 (September 29, 2021): 2565. http://dx.doi.org/10.3390/nano11102565.

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Gold nanoparticles have the potential to be used in biomedical applications from diagnostics to drug delivery. However, interactions of gold nanoparticles with different biomolecules in the cellular environment result in the formation of a “protein corona”—a layer of protein formed around a nanoparticle, which induces changes in the properties of nanoparticles. In this work we developed methods to reproducibly synthesize spheroidal and star-shaped gold nanoparticles, and carried out a physico-chemical characterization of synthesized anionic gold nanospheroids and gold nanostars through transmission electron microscopy (TEM), dynamic light scattering (DLS), zeta potential (ZP), nanoparticles tracking analysis (NTA), ultraviolet-visible (UV–Vis) spectroscopy and estimates of surface-enhanced Raman spectroscopy (SERS) signal enhancement ability. We analyzed how they interact with proteins after pre-incubation with bovine serum albumin (BSA) via UV–Vis, DLS, ZP, NTA, SERS, cryogenic TEM (cryo-TEM) and circular dichroism (CD) spectroscopy. The tests demonstrated that the protein adsorption on the particles’ surfaces was different for spheroidal and star shaped particles. In our experiments, star shaped particles limited the protein corona formation at SERS “hot spots”. This benefits the small-molecule sensing of nanostars in biological media. This work adds more understanding about protein corona formation on gold nanoparticles of different shapes in biological media, and therefore guides design of particles for studies in vitro and in vivo.

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Kont, Ayse, Monique C. P. Mendonça, Michael F. Cronin, Mary R. Cahill, and Caitriona M. O’Driscoll. "Co-Formulation of Amphiphilic Cationic and Anionic Cyclodextrins Forming Nanoparticles for siRNA Delivery in the Treatment of Acute Myeloid Leukaemia." International Journal of Molecular Sciences 23, no. 17 (August 29, 2022): 9791. http://dx.doi.org/10.3390/ijms23179791.

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Non-viral delivery of therapeutic nucleic acids (NA), including siRNA, has potential in the treatment of diseases with high unmet clinical needs such as acute myeloid leukaemia (AML). While cationic biomaterials are frequently used to complex the nucleic acids into nanoparticles, attenuation of charge density is desirable to decrease in vivo toxicity. Here, an anionic amphiphilic CD was synthesised and the structure was confirmed by Fourier-transform infrared spectroscopy (FT-IR), Nuclear Magnetic Resonance (NMR), and high-resolution mass spectrometry (HRMS). A cationic amphiphilic cyclodextrin (CD) was initially used to complex the siRNA and then co-formulated with the anionic amphiphilic CD. Characterisation of the co-formulated NPs indicated a significant reduction in charge from 34 ± 7 mV to 24 ± 6 mV (p < 0.05) and polydispersity index 0.46 ± 0.1 to 0.16 ± 0.04 (p < 0.05), compared to the cationic CD NPs. Size was similar, 161–164 nm, for both formulations. FACS and confocal microscopy, using AML cells (HL-60), indicated a similar level of cellular uptake (60% after 6 h) followed by endosomal escape. The nano co-formulation significantly reduced the charge while maintaining gene silencing (21%). Results indicate that blending of anionic and cationic amphiphilic CDs can produce bespoke NPs with optimised physicochemical properties and potential for enhanced in vivo performance in cancer treatment.

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Tripathi, R. M., Sun-Young Yoon, Dohee Ahn, and Sang J. Chung. "Facile Synthesis of Triangular and Hexagonal Anionic Gold Nanoparticles and Evaluation of Their Cytotoxicity." Nanomaterials 9, no. 12 (December 12, 2019): 1774. http://dx.doi.org/10.3390/nano9121774.

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Comprehension of the shape-dependent properties of gold nanoparticles (AuNPs) could benefit the advancements in cellular uptake efficiency. Spherical AuNPs have generally been used for drug delivery, and recent research has indicated that the cellular uptake of triangular AuNPs was higher than that of spherical ones. Previous reports have also revealed that chemically synthesized AuNPs were cytotoxic. Therefore, we have developed a facile, cost-effective, and environmentally friendly method for synthesizing triangular and hexagonal anionic AuNPs. The zeta potential of the synthesized AuNPs was negative, which indicated that their surface could be easily functionalized with positively charged molecules to upload drugs or biomolecules. Transmission electron microscopy (TEM) images illustrated that the largest particle size of the synthesized quasi-hexagonal AuNPs was 61 nm. The TEM images also illustrated that two types of equilateral-triangular AuNPs were synthesized: One featured sharp and the other rounded corners. The sides of the smallest and largest triangular AuNPs were 23 and 178 nm, respectively. Energy-dispersive X-ray spectra of the green-synthesized AuNPs indicated that they consisted entirely of elemental Au. The cytotoxicity of the green-synthesized AuNPs was evaluated using 3T3-L1 adipocytes. Using cell viability data, we determined that the green-synthesized AuNPs did not exhibit any cytotoxic effects on 3T3-L1 adipocytes.

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Guagliardo, Roberta, Pieterjan Merckx, Agata Zamborlin, Lynn De Backer, Mercedes Echaide, Jesus Pérez-Gil, Stefaan C. De Smedt, and Koen Raemdonck. "Nanocarrier Lipid Composition Modulates the Impact of Pulmonary Surfactant Protein B (SP-B) on Cellular Delivery of siRNA." Pharmaceutics 11, no. 9 (August 23, 2019): 431. http://dx.doi.org/10.3390/pharmaceutics11090431.

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Two decades since the discovery of the RNA interference (RNAi) pathway, we are now witnessing the approval of the first RNAi-based treatments with small interfering RNA (siRNA) drugs. Nevertheless, the widespread use of siRNA is limited by various extra- and intracellular barriers, requiring its encapsulation in a suitable (nanosized) delivery system. On the intracellular level, the endosomal membrane is a major barrier following endocytosis of siRNA-loaded nanoparticles in target cells and innovative materials to promote cytosolic siRNA delivery are highly sought after. We previously identified the endogenous lung surfactant protein B (SP-B) as siRNA delivery enhancer when reconstituted in (proteo) lipid-coated nanogels. It is known that the surface-active function of SP-B in the lung is influenced by the lipid composition of the lung surfactant. Here, we investigated the role of the lipid component on the siRNA delivery-promoting activity of SP-B proteolipid-coated nanogels in more detail. Our results clearly indicate that SP-B prefers fluid membranes with cholesterol not exceeding physiological levels. In addition, SP-B retains its activity in the presence of different classes of anionic lipids. In contrast, comparable fractions of SP-B did not promote the siRNA delivery potential of DOTAP:DOPE cationic liposomes. Finally, we demonstrate that the beneficial effect of lung surfactant on siRNA delivery is not limited to lung-related cell types, providing broader therapeutic opportunities in other tissues as well.

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Mazzaglia, Antonino, Norberto Micali, Luigi Monsù Scolaro, Maria Teresa Sciortino, Salvatore Sortino, and Valentina Villari. "Design of photosensitizer/cyclodextrin nanoassemblies: spectroscopy, intracellular delivery and photodamage." Journal of Porphyrins and Phthalocyanines 14, no. 08 (August 2010): 661–77. http://dx.doi.org/10.1142/s1088424610002562.

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The engineering of multifunctional nanoparticles carrying photosensitizer drugs (PS) and exposing binding groups for cellular receptors is of increasing interest in therapeutics and diagnostics applications. Natural and modified cyclodextrins (CDs) offer useful scaffolds to bind PS guests by supramolecular interactions. In particular, amphiphilic β-CDs, which form nanoaggregates of diverse shape and size according to the polarity of substituent groups on the rims, include in their different compartments as CD cavity, hydrophilic and hydrophobic portion, PS with different physicochemical properties. PS embedded in cationic amphiphilic CD nanoassemblies are effective in inducing photodynamic damage in cancer cells. For a carrier/PS system to be used in photodynamic therapy (PDT) or photodynamic diagnosis (PDD), the appropriate combination of the delivery characteristics with the preservation of the photodynamic activity of the PS is strictly required. Homogeneous multilayer films based on cationic amphiphilic β-CD entrapping anionic porphyrins can be constructed to exploit interfacial electrostatic interactions between the two components. The capability of CDs to generate restricted microenvironments for PS which can facilitate photoinduced energy transfer with suitable donor molecules was investigated for potential application in fluorescence diagnosis. Besides, recent findings suggest that PDT could represent a useful tool for properly addressing an alternative approach for killing pathogens and combating infections at a clinical level. Finally, modified CDs can bind gold nanoparticles, yielding hybrid organic/inorganic nanoparticles which were studied in water solution and after casting on solid substrates. These binary assemblies could further encapsulate PS or other conventional drugs, opening new intriguing routes on multimodal therapy.

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Khalil, Ali, Saad Saba, Catherine Ribault, Manuel Vlach, Pascal Loyer, Olivier Coulembier, and Sandrine Cammas-Marion. "Synthesis of Poly(Dimethylmalic Acid) Homo- and Copolymers to Produce Biodegradable Nanoparticles for Drug Delivery: Cell Uptake and Biocompatibility Evaluation in Human Heparg Hepatoma Cells." Polymers 12, no. 8 (July 29, 2020): 1705. http://dx.doi.org/10.3390/polym12081705.

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Hydrophobic and amphiphilic derivatives of the biocompatible and biodegradable poly(dimethylmalic acid) (PdiMeMLA), varying by the nature of the lateral chains and the length of each block, respectively, have been synthesized by anionic ring-opening polymerization (aROP) of the corresponding monomers using an initiator/base system, which allowed for very good control over the (co)polymers’ characteristics (molar masses, dispersity, nature of end-chains). Hydrophobic and core-shell nanoparticles (NPs) were then prepared by nanoprecipitation of hydrophobic homopolymers and amphiphilic block copolymers, respectively. Negatively charged NPs, showing hydrodynamic diameters (Dh) between 50 and 130 nm and narrow size distributions (0.08 < PDI < 0.22) depending on the (co)polymers nature, were obtained and characterized by dynamic light scattering (DLS), zetametry, and transmission electron microscopy (TEM). Finally, the cytotoxicity and cellular uptake of the obtained NPs were evaluated in vitro using the hepatoma HepaRG cell line. Our results showed that both cytotoxicity and cellular uptake were influenced by the nature of the (co)polymer constituting the NPs.

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Straehla, Joelle, Cynthia Hajal, Hannah Safford, Giovanni Offeddu, Jeffrey Wyckoff, Roger Kamm, and Paula Hammond. "EXTH-26. LAYER-BY-LAYER NANOPARTICLES DESIGNED FOR DUAL BLOOD-BRAIN BARRIER AND GLIOMA TARGETING." Neuro-Oncology 23, Supplement_6 (November 2, 2021): vi168—vi169. http://dx.doi.org/10.1093/neuonc/noab196.665.

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Abstract BACKGROUND While biologically diverse, high grade gliomas (HGGs) have a dismal prognosis in both adults and children. Promising therapeutics have been identified for HGGs based on common genomic alterations and aberrant signaling pathways, but achieving effective drug exposure at the tumor site remains a challenge largely due to the blood-brain barrier (BBB). HYPOTHESIS: A tunable nanocarrier platform can improve nanoparticle delivery across the (BBB) and into glioma cells. METHODS We synthesized layer-by-layer nanoparticles by coating anionic, fluorescent liposomes with nanometers-thick layers of oppositely charged polyelectrolytes, creating a library of organic, nontoxic drug carriers with varied surface chemistries. We characterized the library using dynamic light scattering and quantified interactions with a range of pediatric and adult glioma cell lines using flow cytometry. We used intravital two-photon microscopy to quantify nanoparticle trafficking across the intact BBB through a cranial window in anesthetized mice. RESULTS Nanoparticle surface chemistry strongly influences cellular trafficking in vitro, with two polymers identified as particularly high-performing across brain tumors lines: poly-L-aspartic acid (semi-synthetic) and hyaluronic acid (natural polysaccharide). The addition of the angiopep-2 targeting moiety onto these polymers improved nanoparticle uptake into brain microvascular endothelial cells in vitro without abrogating tumor affinity. We developed a new algorithm to quantify permeability of fluorescent compounds across the BBB in vivo and validated our method by measuring dextran permeability at varied molecular weights. In our initial study in non-tumor-bearing mice (n=12), we successfully quantified nanoparticle permeability across the BBB. In this study, surface functionalization did not increase BBB permeability above the control nanoparticle, though it did improve nanoparticle half-life in circulation and may still impart a therapeutic benefit when loaded with drug. Additional investigations in orthotopic tumor-bearing mice are ongoing. In summary, we report the development of layer-by-layer nanocarriers as a modular drug delivery platform with therapeutic potential for gliomas.

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Kim, Tae-Hyun, Gyeong Jin Lee, Joo-Hee Kang, Hyoung-Jun Kim, Tae-il Kim, and Jae-Min Oh. "Anticancer Drug-Incorporated Layered Double Hydroxide Nanohybrids and Their Enhanced Anticancer Therapeutic Efficacy in Combination Cancer Treatment." BioMed Research International 2014 (2014): 1–11. http://dx.doi.org/10.1155/2014/193401.

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Objective. Layered double hydroxide (LDH) nanoparticles have been studied as cellular delivery carriers for anionic anticancer agents. As MTX and 5-FU are clinically utilized anticancer drugs in combination therapy, we aimed to enhance the therapeutic performance with the help of LDH nanoparticles.Method. Anticancer drugs, MTX and 5-FU, and their combination, were incorporated into LDH by reconstruction method. Simply, LDHs were thermally pretreated at 400°C, and then reacted with drug solution to simultaneously form drug-incorporated LDH. Thus prepared MTX/LDH (ML), 5-FU/LDH (FL), and (MTX + 5-FU)/LDH (MFL) nanohybrids were characterized by X-ray diffractometer, scanning electron microscopy, infrared spectroscopy, thermal analysis, zeta potential measurement, dynamic light scattering, and so forth. The nanohybrids were administrated to the human cervical adenocarcinoma, HeLa cells, in concentration-dependent manner, comparing with drug itself to verify the enhanced therapeutic efficacy.Conclusion. All the nanohybrids successfully accommodated intended drug molecules in their house-of-card-like structures during reconstruction reaction. It was found that the anticancer efficacy of MFL nanohybrid was higher than other nanohybrids, free drugs, or their mixtures, which means the multidrug-incorporated LDH nanohybrids could be potential drug delivery carriers for efficient cancer treatment via combination therapy.

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Tseu, Gloria Yi Wei, and Khairul Azfar Kamaruzaman. "A Review of Different Types of Liposomes and Their Advancements as a Form of Gene Therapy Treatment for Breast Cancer." Molecules 28, no. 3 (February 3, 2023): 1498. http://dx.doi.org/10.3390/molecules28031498.

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Breast cancer incidence and mortality rates have increased exponentially during the last decade, particularly among female patients. Current therapies, including surgery and chemotherapy, have significant negative physical and mental impacts on patients. As a safer alternative, gene therapy utilising a therapeutic gene with the potential to treat various ailments is being considered. Delivery of the gene generally utilises viral vectors. However, immunological reactions and even mortality have been recorded as side effects. As a result, non-viral vectors, such as liposomes, a system composed of lipid bilayers formed into nanoparticles, are being studied. Liposomes have demonstrated tremendous potential due to their limitless ability to combine many functions into a system with desirable characteristics and functionality. This article discusses cationic, anionic, and neutral liposomes with their stability, cytotoxicity, transfection ability, cellular uptake, and limitation as a gene carrier suitable for gene therapy specifically for cancer. Due to the more practical approach of employing electrostatic contact with the negatively charged nucleic acid and the cell membrane for absorption purposes, cationic liposomes appear to be more suited for formulation for gene delivery and therapy for breast cancer treatment. As the other alternatives have numerous complicated additional modifications, attachments need to be made to achieve a functional gene therapy system for breast cancer treatment, which were also discussed in this review. This review aimed to increase understanding and build a viable breast cancer gene therapy treatment strategy.

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Busmann, Eike Folker, and Henrike Lucas. "Particle Engineering of Innovative Nanoemulsion Designs to Modify the Accumulation in Female Sex Organs by Particle Size and Surface Charge." Pharmaceutics 14, no. 2 (January 27, 2022): 301. http://dx.doi.org/10.3390/pharmaceutics14020301.

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Particle engineering of nanosized drug delivery systems (DDS) can be used as a strategic tool to influence their pharmacokinetics after intravenous (i.v.) application by the targeted adaptation of their particle properties according to the needs at their site of action. This study aimed to investigate particle properties depending on patterns in the biodistribution profile to modify the accumulation in the female sex organs using tailor-made nanoemulsion designs and thereby to either increase therapeutic efficiency for ovarian dysfunctions and diseases or to decrease the side effects caused by unintended accumulation. Through the incorporation of the anionic phospholipid phosphatidylglycerol (PG) into the stabilizing macrogol 15 hydroxystearate (MHS) layer of the nanoemulsions droplets, it was possible to produce tailor-made nanoparticles with tunable particle size between 25 to 150 nm in diameter as well as tunable surface charges between −2 to nearly −30 mV zeta potential using a phase inversion-based process. Three chosen negatively surface-charged nanoemulsions of 50, 100, and 150 nm in diameter showed very low cellular toxicities on 3T3 and NHDF fibroblasts and merely interacted with the blood cells, but instead stayed inert in the plasma. In vivo and ex vivo fluorescence imaging of adult female mice i.v. injected with the negatively surface-charged nanoemulsions revealed a high accumulation depending on their particle size in the reticuloendothelial system (RES), being found in the liver and spleen with a mean portion of the average radiant efficiency (PARE) between 42–52%, or 8–10%, respectively. With increasing particle size, an accumulation in the heart was detected with a mean PARE up to 8%. These three negatively surface-charged nanoemulsions overcame the particle size-dependent accumulation in the female sex organs and accumulated equally with a small mean PARE of 5%, suitable to reduce the side effects caused by unintended accumulation while maintaining different biodistribution profiles. In contrast, previously investigated neutral surface-charged nanoemulsions accumulated with a mean PARE up to 10%, strongly dependent on their particle sizes, which is useful to improve the therapeutic efficacy for ovarian dysfunctions and diseases.

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Das, Horváth, Šafranko, Jokić, Széchenyi, and Kőszegi. "Antimicrobial Activity of Chamomile Essential Oil: Effect of Different Formulations." Molecules 24, no. 23 (November 26, 2019): 4321. http://dx.doi.org/10.3390/molecules24234321.

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Essential oils (EOs) are highly lipophilic, which makes the measurement of their biological action difficult in an aqueous environment. We formulated a Pickering nanoemulsion of chamomile EO (CPe). Surface-modified Stöber silica nanoparticles (20 nm) were prepared and used as a stabilizing agent of CPe. The antimicrobial activity of CPe was compared with that of emulsion stabilized with Tween 80 (CT80) and ethanolic solution (CEt). The antimicrobial effects were assessed by their minimum inhibitory concentration (MIC90) and minimum effective (MEC10) concentrations. Besides growth inhibition (CFU/mL), the metabolic activity and viability of Gram-positive and Gram-negative bacteria as well as Candida species, in addition to the generation of oxygen free radical species (ROS), were studied. We followed the killing activity of CPe and analyzed the efficiency of the EO delivery for examined formulations by using unilamellar liposomes as a cellular model. CPe showed significantly higher antibacterial and antifungal activities than CT80 and CEt. Chamomile EOs generated superoxide anion and peroxide related oxidative stress which might be the major mode of action of Ch essential oil. We could also demonstrate that CPe was the most effective in donation of the active EO components when compared with CT80 and CEt. Our data suggest that CPe formulation is useful in the fight against microbial infections.

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Das, Sourav, Barbara Vörös-Horváth, Tímea Bencsik, Giuseppe Micalizzi, Luigi Mondello, Györgyi Horváth, Tamás Kőszegi, and Aleksandar Széchenyi. "Antimicrobial Activity of Different Artemisia Essential Oil Formulations." Molecules 25, no. 10 (May 21, 2020): 2390. http://dx.doi.org/10.3390/molecules25102390.

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The extreme lipophilicity of essential oils (EOs) impedes the measurement of their biological actions in an aqueous environment. We formulated oil in water type Pickering Artemisia annua EO nanoemulsions (AEP) with surface-modified Stöber silica nanoparticles (20 nm) as the stabilizing agent. The antimicrobial activity of AEP and its effects on mature Candida biofilms were compared with those of Tween 80 stabilized emulsion (AET) and ethanolic solution (AEE) of the Artemisia EO. The antimicrobial activity was evaluated by using the minimum inhibitory concentrations (MIC90) and minimum effective concentrations (MEC10) of the compounds. On planktonic bacterial and fungal cells beside growth inhibition, colony formation (CFU/mL), metabolic activity, viability, intracellular ATP/total protein (ATP/TP), along with reactive oxygen species (ROS) were also studied. Artemisia annua EO nanoemulsion (AEP) showed significantly higher antimicrobial activity than AET and AEE. Artemisia annua EO nanoemulsions (AEP) generated superoxide anion and peroxides-related oxidative stress, which might be the underlying mode of action of the Artemisia EO. Unilamellar liposomes, as a cellular model, were used to examine the delivery efficacy of the EO of our tested formulations. We could demonstrate higher effectiveness of AEP in the EO components’ donation compared to AET and AEE. Our data suggest the superiority of the AEP formulation against microbial infections.

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Uchida, Noriyuki, Masayoshi Yanagi, and Hiroki Hamada. "Transdermal Delivery of Anionic Phospholipid Nanoparticles Containing Fullerene." Natural Product Communications 17, no. 2 (February 2022): 1934578X2210784. http://dx.doi.org/10.1177/1934578x221078444.

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In this work, we prepared a transparent dispersion of fullerene nanoparticles by sonication with anionic phospholipids of 1,2-dipalmitoyl-sn-glycero-3-phosphorylglycerol (DPPG) with fluorescently NBD-labeled 1,2-dipalmitoyl-sn-glycero-3-phosphorylethanolamine (DPPE). Upon incubation of the fullerene nanoparticles with a rat skin, the nanoparticles successfully penetrated the stratum corneum and reached the epidermis.

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Yuan, Hong, Wei Zhang, Yong-Zhong Du, and Fu-Qiang Hu. "Ternary nanoparticles of anionic lipid nanoparticles/protamine/DNA for gene delivery." International Journal of Pharmaceutics 392, no. 1-2 (June 15, 2010): 224–31. http://dx.doi.org/10.1016/j.ijpharm.2010.03.025.

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Parlea, Lorena, Anu Puri, Wojciech Kasprzak, Eckart Bindewald, Paul Zakrevsky, Emily Satterwhite, Kenya Joseph, Kirill A. Afonin, and Bruce A. Shapiro. "Cellular Delivery of RNA Nanoparticles." ACS Combinatorial Science 18, no. 9 (August 26, 2016): 527–47. http://dx.doi.org/10.1021/acscombsci.6b00073.

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Faraji, Amir H., and Peter Wipf. "Nanoparticles in cellular drug delivery." Bioorganic & Medicinal Chemistry 17, no. 8 (April 2009): 2950–62. http://dx.doi.org/10.1016/j.bmc.2009.02.043.

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Uchida, Noriyuki, Masayoshi Yanagi, and Hiroki Hamada. "Piceid Nanoparticles Stabilized by Anionic Phospholipids for Transdermal Delivery." Natural Product Communications 15, no. 5 (May 2020): 1934578X2092557. http://dx.doi.org/10.1177/1934578x20925578.

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Piceid, stilbenoid glucoside, is a representative resveratrol derivative. Because of a high tyrosinase inhibitory activity of piceid through resveratrol derivatives, transdermal delivery of piceid has been desired for taking advantage of the activity. Here we successfully prepared composite nanoparticles composed of anionic phospholipid of 1,2-dipalmitoyl- sn-glycero-3-phosphorylglycerol (DPPG) and piceid by mixing them in water and a subsequent heating/cooling process. When small-sized fluorescently labeled DPPG-piceid (DPPG-FLpiceid) nanoparticles were added to rat skin tissue, FLpiceid molecules were localized in stratum corneum.

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Pamujula, Sarala, Sidhartha Hazari, Gevoni Bolden, Richard A. Graves, Dakshinamurthy Devanga Chinta, Srikanta Dash, Vimal Kishore, and Tarun K. Mandal. "Cellular delivery of PEGylated PLGA nanoparticles." Journal of Pharmacy and Pharmacology 64, no. 1 (November 24, 2011): 61–67. http://dx.doi.org/10.1111/j.2042-7158.2011.01376.x.

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Huang, Xiaomeng, Sebastian Schwind, Ann-Kathrin Eisfeld, Bo Yu, Ramasamy Santhanam, Pia Hoellerbauer, Yan Jin, et al. "Therapeutic Targeting of the RAS-Pathway by Synthetic Mir-181a Nanoparticles in Acute Myeloid Leukemia (AML)." Blood 120, no. 21 (November 16, 2012): 2422. http://dx.doi.org/10.1182/blood.v120.21.2422.2422.

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Abstract Abstract 2422 Today most AML patients (pts) still fail to achieve long-term survival. New therapeutic options are needed. We and others reported that high miR-181a expression associated with better outcomes in AML pts (Marcucci et al NEJM 2008; Schwind et al JCO 2010; Li et al Blood 2012), but the underlying mechanisms remain unclear. Aberrant RAS activation by mutations or overexpression is frequent in human malignancies, including AML. Previously KRAS was described as a direct miR-181a target in oral squamous cell carcinoma (Shin et al BBRC 2011). Here we confirmed KRAS as a direct miR-181a target & identified miR-181a-binding sites in the MAPK1 untranslated region (UTR) utilizing in silico tools & consequently identified MAPK1 as a new direct miR-181a target of the RAS signaling pathway. We observed respectively a 30±5% (±standard deviation; P=.003) & 35±2% (P=.0002) downregulation of luciferase activity after co-transfecting 293T cells with miR-181a mimic vs scramble control (sc) molecules and luciferase reporter constructs spanning the predicted miR-181a binding sites (seed sequences) in KRAS or MAPK1. Mutations in the seed sequences of KRAS or MAPK1 could rescue the miR-181a mimic induced downregulation. In the KG1a & OCI-AML3 AML cells with low endogenous miR-181a level but activated RAS-signaling, lentiviral miR-181a overexpression reduced KRAS protein by 2.8 & 2.1 fold and MAPK1 by 2.8 & 1.5 fold (normalized to β-actin & quantified by densitometry) respectively compared to sc expressing controls. Consistent with this result, lentiviral-based knock-down of miR-181a increased KRAS by 1.4 & 3.2 fold and MAPK1 protein by 2.3 & 1.8 fold in KG1a & OCI-AML3 cells respectively, compared to sc controls. Since higher miR-181a associated with improved outcomes & miR-181a targets the RAS-pathway in AML, increasing miR-181a may have therapeutic value for AML pts. We formulated transferrin (Tf) targeted anionic lipid based lipopolyplex nanoparticles (NP) to deliver synthetic miR-181a mimic molecules to AML cells which overexpress Tf receptors, while overcoming RNA degradation & facilitating the cellular uptake of the miR molecules. Mature miR-181a in KG1a, OCI-AML3 cells & pts blasts (n=3) were measured by qPCR after treatment with Tf conjugated NP (TfNP) encapsulating miR-181a mimic molecules (TfNP181a) or sc (TfNPsc) at 10 nM. After 24h mature miR-181a levels increased 211±31, 880±10 & 145±19 fold in KG1a, OCI-AML3 & pts blasts (n=3), while levels of miR-181b & unrelated miR-140 remained unchanged. We found that delivered miR-181a downregulated KRAS & MAPK1 proteins (KG1a: 2.5 & 2.1 fold; OCI-AML3: 2.5 & 2.4 fold; pts blasts: 9.0 & 5.8 fold respectively) compared to TfNPsc treatment. To analyze downstream effects of TfNP181a mediated inhibition of the RAS pathway we assessed the expression of total MEK & AKT and p-MEK & p-AKT. TfNP181a compared to TfNPsc treatment decreased p-MEK by 3.2, 2.1 & 5 fold and p-AKT by 2.9, 3.6 & 6.5 fold in KG1a, OCI-AML3 & pts blasts. Furthermore, a 3.2, 4.7 & 3.1 fold reduction of the transcription factor MYC, which is regulated by MAPK in KG1a, OCI-AML3 & pts blasts treated with TfNP181a vs TfNPsc was observed. TfNP181a treatment also resulted in antileukemic activity. TfNP181a compared to TfNPsc treatment led to reduced proliferation of KG1a (34±8% at day 4, P=.01) & OCI-AML3 (31±4% at day 4, P=.02) cells, and decreased colony formation (after 2 weeks) in both cell lines by 40±5% (P<.01) & 44±5% (P<.0001) respectively. Since higher miR-181a levels associated with improved treatment response we next tested whether TfNP181a could sensitize AML cells to daunorubicin (DNR). After 24h priming with 10 nM TfNP181a or TfNPsc, KG1a & OCI-AML3 cells were treated with 0.2 μM DNR for 72h. MTS assays showed decreased viability of the cells primed with TfNP181a vs TfNPsc: 66% vs 80.6% (P=.01) and 58% vs 81% (P=.02) for KG1a & OCI-AML3 respectively. We confirmed these findings in pts blasts primed with TfNP181a: 62.4% vs TfNPsc: 96.5% (P<.01). Preclinical in vivo tests of TfNP181a are ongoing. In conclusion we first report that miR-181a targets KRAS and its downstream effector MAPK1 in AML. TfNP181a treatment resulted in reduced RAS expression & signaling inhibition, antileukemic activity & increased sensitivity to chemotherapy in AML cells. Developing TfNP181a for miR-181a replacement therapy may represent a novel therapeutic approach to AML & may be extended to other malignancies involving RAS signaling. Disclosures: No relevant conflicts of interest to declare.

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Chavanpatil, Mahesh D., Ayman Khdair, and Jayanth Panyam. "Nanoparticles for Cellular Drug Delivery: Mechanisms and Factors Influencing Delivery." Journal of Nanoscience and Nanotechnology 6, no. 9 (September 1, 2006): 2651–63. http://dx.doi.org/10.1166/jnn.2006.443.

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Polymeric nanoparticles have demonstrated enormous potential as cellular drug delivery vehicles. Nanoparticles improve drug's stability as well as its availability and retention at the target intracellular site of action. Therapeutic efficacy of nanoparticles can be further enhanced by conjugating specific ligands to nanoparticle surface. Ligand conjugation can also be used to favorably modify the intracellular disposition of nanoparticles. A number of ligands are available for this purpose; use of a specific ligand depends on the target cell, the material used for nanoparticle formulation, and the chemistry available for ligand-nanoparticle conjugation. Cellular drug delivery using nanoparticles is also affected by clearance through the reticuloendothelial system. In this paper, we review the recent progress on our understanding of physicochemical factors that affect the cellular uptake of nanoparticles and the different cellular processes that could be exploited to enhance nanoparticle uptake into cells.

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Wendorf, Janet, James Chesko, Jina Kazzaz, Mildred Ugozzoli, Michael Vajdy, Derek O'Hagan, and Manmohan Singh. "A comparison of anionic nanoparticles and microparticles as vaccine delivery systems." Human Vaccines 4, no. 1 (January 2008): 44–49. http://dx.doi.org/10.4161/hv.4.1.4886.

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Mocanu, G., M. Nichifor, L. Picton, E. About-Jaudet, and D. Le Cerf. "Preparation and characterization of anionic pullulan thermoassociative nanoparticles for drug delivery." Carbohydrate Polymers 111 (October 2014): 892–900. http://dx.doi.org/10.1016/j.carbpol.2014.05.037.

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Uchida, Noriyuki, Masayoshi Yanagi, Kei shimoda, and Hiroki Hamada. "Transdermal Delivery of Small-Sized Resveratrol Nanoparticles to Epidermis Using Anionic Phospholipids." Natural Product Communications 15, no. 9 (September 2020): 1934578X2095144. http://dx.doi.org/10.1177/1934578x20951443.

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Composite nanoparticles composed of anionic phospholipid of 1,2-dipalmitoyl- sn-glycero-3-phosphorylglycerol (DPPG) and resveratrol (Res) were successfully prepared by mixing them in water and a subsequent heating/cooling process. Small-sized DPPG-Res nanoparticles (<60 nm) could be prepared by ultrasonic fragmentation. Upon addition of size-controlled fluorescently labeled Res (FLRes) nanoparticles stabilized with DPPG (DPPG-FLRes) to rat skin tissue, FLRes molecules infiltrated into the epidermis layer permeating stratum corneum.

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Hussain, Majad, Mikhail Shchepinov, Muhammad Sohail, Ibrahim F. Benter, Andrew J. Hollins, Edwin M. Southern, and Saghir Akhtar. "A novel anionic dendrimer for improved cellular delivery of antisense oligonucleotides." Journal of Controlled Release 99, no. 1 (September 2004): 139–55. http://dx.doi.org/10.1016/j.jconrel.2004.06.009.

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Insua, Ignacio, Evangelos Liamas, Zhenyu Zhang, Anna F. A. Peacock, Anne Marie Krachler, and Francisco Fernandez-Trillo. "Enzyme-responsive polyion complex (PIC) nanoparticles for the targeted delivery of antimicrobial polymers." Polymer Chemistry 7, no. 15 (2016): 2684–90. http://dx.doi.org/10.1039/c6py00146g.

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Here we present new enzyme-responsive polyion complex (PIC) nanoparticles prepared from antimicrobial poly(ethylene imine) and an anionic enzyme-responsive peptide targetingPseudomonas aeruginosa's elastase.

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Uchida, Noriyuki, Masayoshi Yanagi, and Hiroki Hamada. "Size-Tunable Paclitaxel Nanoparticles Stabilized by Anionic Phospholipids for Transdermal Delivery Applications." Natural Product Communications 15, no. 3 (March 1, 2020): 1934578X1990068. http://dx.doi.org/10.1177/1934578x19900684.

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Composite nanoparticles composed of an anionic phospholipid of 1,2-dipalmitoyl-sn-glycero-3-phosphorylglycerol (DPPG) and paclitaxel (PTX) were successfully prepared by mixing them in water followed by a subsequent heating/cooling process. The size of DPPG-PTX nanoparticle could be easily tuned by ultrasonic fragmentation. Upon addition of small-sized fluorescently labeled paclitaxel (FLPTX) nanoparticles with DPPG (DPPG-FLPTX) to rat skin tissue, part of the FLPTX molecules permeated to the stratum corneum.

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Feng, Song, Sisi Cui, Jing Jin, and Yueqing Gu. "Macrophage as cellular vehicles for delivery of nanoparticles." Journal of Innovative Optical Health Sciences 07, no. 03 (May 2014): 1450023. http://dx.doi.org/10.1142/s1793545814500230.

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Treatment of malignant brain tumors continues to challenge scientists and clinicians alike. Location of these tumors within the central nervous system (CNS), which is considered a "privileged" organ, can prevent the penetration of chemotherapeutic agents through the blood–brain barrier (BBB). To overcome this limitation, nanoparticles are taken up and transported by macrophage and then delivered directly into the CNS. In this study, we used macrophage to uptake the folate-targeted bifunctional micelles loaded with near-infrared (NIR) dye ICG-Der-01 and investigate the dynamic bio-distributions of macrophage after intravenous injection into tumor-bearing mice. In vitro cellular experiments by confocal microscopy indicated that the uptake of micelles in macrophage was greatly enhanced due to the folate receptor overexpression. Dynamic bio-distributions of macrophage showed a rapid clearing rate through the liver intestine pathway. In conclusion, macrophage could potentially be used as nanoparticle drug carriers and require further investigation.

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Xu, Zhi Ping, Qing Hua Zeng, Gao Qing Lu, and Ai Bing Yu. "Inorganic nanoparticles as carriers for efficient cellular delivery." Chemical Engineering Science 61, no. 3 (February 2006): 1027–40. http://dx.doi.org/10.1016/j.ces.2005.06.019.

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Lamson, Nicholas G., Adrian Berger, Katherine C. Fein, and Kathryn A. Whitehead. "Anionic nanoparticles enable the oral delivery of proteins by enhancing intestinal permeability." Nature Biomedical Engineering 4, no. 1 (November 4, 2019): 84–96. http://dx.doi.org/10.1038/s41551-019-0465-5.

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Soto, Ernesto R., Abaigeal C. Caras, Lindsey C. Kut, Melissa K. Castle, and Gary R. Ostroff. "Glucan Particles for Macrophage Targeted Delivery of Nanoparticles." Journal of Drug Delivery 2012 (October 13, 2012): 1–13. http://dx.doi.org/10.1155/2012/143524.

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Glucan particles (GPs) are hollow, porous 2–4 μm microspheres derived from the cell walls of Baker's yeast (Saccharomyces cerevisiae). The 1,3-β-glucan outer shell provides for receptor-mediated uptake by phagocytic cells expressing β-glucan receptors. GPs have been used for macrophage-targeted delivery of soluble payloads (DNA, siRNA, protein, and small molecules) encapsulated inside the hollow GPs via core polyplex and layer-by-layer (LbL) synthetic strategies. In this communication, we report the incorporation of nanoparticles as cores inside GPs (GP-NP) or electrostatically bound to the surface of chemically derivatized GPs (NP-GP). GP nanoparticle formulations benefit from the drug encapsulation properties of NPs and the macrophage-targeting properties of GPs. GP nanoparticle formulations were synthesized using fluorescent anionic polystyrene nanoparticles allowing visualization and quantitation of NP binding and encapsulation. Mesoporous silica nanoparticles (MSNs) containing the chemotherapeutic doxorubicin (Dox) were bound to cationic GPs. Dox-MSN-GPs efficiently delivered Dox into GP phagocytic cells resulting in enhanced Dox-mediated growth arrest.

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Mitrach, Franziska, Maximilian Schmid, Magali Toussaint, Sladjana Dukic-Stefanovic, Winnie Deuther-Conrad, Heike Franke, Alexander Ewe, et al. "Amphiphilic Anionic Oligomer-Stabilized Calcium Phosphate Nanoparticles with Prospects in siRNA Delivery via Convection-Enhanced Delivery." Pharmaceutics 14, no. 2 (January 29, 2022): 326. http://dx.doi.org/10.3390/pharmaceutics14020326.

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Convection-enhanced delivery (CED) has been introduced as a concept in cancer treatment to generate high local concentrations of anticancer therapeutics and overcome the limited diffusional distribution, e.g., in the brain. RNA interference provides interesting therapeutic options to fight cancer cells but requires nanoparticulate (NP) carriers with a size below 100 nm as well as a low zeta potential for CED application. In this study, we investigated calcium phosphate NPs (CaP-NPs) as siRNA carriers for CED application. Since CaP-NPs tend to aggregate, we introduced a new terpolymer (o14PEGMA(1:1:2.5) NH3) for stabilization of CaP-NPs intended for delivery of siRNA to brain cancer cells. This small terpolymer provides PEG chains for steric stabilization, and a fat alcohol to improve interfacial activity, as well as maleic anhydrides that allow for both labeling and high affinity to Ca(II) in the hydrolyzed state. In a systematic approach, we varied the Ca/P ratio as well as the terpolymer concentration and successfully stabilized NPs with the desired properties. Labeling of the terpolymer with the fluorescent dye Cy5 revealed the terpolymer’s high affinity to CaP. Importantly, we also determined a high efficiency of siRNA binding to the NPs that caused very effective survivin siRNA silencing in F98 rat brain cancer cells. Cytotoxicity investigations with a standard cell line resulted in minor and transient effects; no adverse effects were observed in organotypic brain slice cultures. However, more specific cytotoxicity investigations are required. This study provides a systematic and mechanistic analysis characterizing the effects of the first oligomer of a new class of stabilizers for siRNA-loaded CaP-NPs.

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Liu, Yang, Ziyuan Song, Nan Zheng, Kenya Nagasaka, Lichen Yin, and Jianjun Cheng. "Systemic siRNA delivery to tumors by cell-penetrating α-helical polypeptide-based metastable nanoparticles." Nanoscale 10, no. 32 (2018): 15339–49. http://dx.doi.org/10.1039/c8nr03976c.

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Metastable nanoparticles capable of tumor targeting, tumor penetration, and selective tumor cell internalization were developed based on membrane penetrating, helical polypeptide PVBLG-8 and anionic PLG, for the efficient encapsulation and delivery of EGFR siRNA.

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Știufiuc, Gabriela Fabiola, Ștefan Nițică, Valentin Toma, Cristian Iacoviță, Dietrich Zahn, Romulus Tetean, Emil Burzo, Constantin Mihai Lucaciu, and Rareș Ionuț Știufiuc. "Synergistical Use of Electrostatic and Hydrophobic Interactions for the Synthesis of a New Class of Multifunctional Nanohybrids: Plasmonic Magneto-Liposomes." Nanomaterials 9, no. 11 (November 15, 2019): 1623. http://dx.doi.org/10.3390/nano9111623.

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By carefully controlling the electrostatic interactions between cationic liposomes, which already incorporate magnetic nanoparticles in the bilayers, and anionic gold nanoparticles, a new class of versatile multifunctional nanohybrids (plasmonic magneto-liposomes) that could have a major impact in drug delivery and controlled release applications has been synthesized. The experimental results confirmed the successful synthesis of hydrophobic superparamagnetic iron oxide nanoparticles (SPIONs) and polyethylene glycol functionalized (PEGylated) gold nanoparticles (AuNPs). The SPIONs were incorporated in the liposomal lipidic bilayers, thus promoting the formation of cationic magnetoliposomes. Different concentrations of SPIONs were loaded in the membrane. The cationic magnetoliposomes were decorated with anionic PEGylated gold nanoparticles using electrostatic interactions. The successful incorporation of SPIONs together with the modifications they generate in the bilayer were analyzed using Raman spectroscopy. The plasmonic properties of the multifunctional nanohybrids were investigated using UV-Vis absorption and (surface-enhanced) Raman spectroscopy. Their hyperthermic properties were recorded at different frequencies and magnetic field intensities. After the synthesis, the nanosystems were extensively characterized in order to properly evaluate their potential use in drug delivery applications and controlled release as a result of the interaction with an external stimulus, such as an NIR laser or alternating magnetic field.

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Garg, Ashish, Sweta Garg, Nitendra K. Sahu, Sarita Rani, Umesh Gupta, and Awesh K. Yadav. "Heparin appended ADH-anionic polysaccharide nanoparticles for site-specific delivery of usnic acid." International Journal of Pharmaceutics 557 (February 2019): 238–53. http://dx.doi.org/10.1016/j.ijpharm.2018.12.049.

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Kim, Hyungjin, Takami Akagi, and Mitsuru Akashi. "Preparation of CpG ODN-encapsulated Anionic Poly(amino acid) Nanoparticles for Gene Delivery." Chemistry Letters 39, no. 3 (March 5, 2010): 278–79. http://dx.doi.org/10.1246/cl.2010.278.

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Heidel, Jeremy D., and Thomas Schluep. "Cyclodextrin-Containing Polymers: Versatile Platforms of Drug Delivery Materials." Journal of Drug Delivery 2012 (February 1, 2012): 1–17. http://dx.doi.org/10.1155/2012/262731.

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Nanoparticles are being widely explored as potential therapeutics for numerous applications in medicine and have been shown to significantly improve the circulation, biodistribution, efficacy, and safety profiles of multiple classes of drugs. One leading class of nanoparticles involves the use of linear, cyclodextrin-containing polymers (CDPs). As is discussed in this paper, CDPs can incorporate therapeutic payloads into nanoparticles via covalent attachment of prodrug/drug molecules to the polymer (the basis of the Cyclosert platform) or by noncovalent inclusion of cationic CDPs to anionic, nucleic acid payloads (the basis of the RONDEL platform). For each of these two approaches, we review the relevant molecular architecture and its rationale, discuss the physicochemical and biological properties of these nanoparticles, and detail the progress of leading drug candidates for each that have achieved clinical evaluation. Finally, we look ahead to potential future directions of investigation and product candidates based upon this technology.

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Niu, Yuting, Meihua Yu, Sandy B. Hartono, Jie Yang, Hongyi Xu, Hongwei Zhang, Jun Zhang, et al. "Nanoparticles Mimicking Viral Surface Topography for Enhanced Cellular Delivery." Advanced Materials 25, no. 43 (August 15, 2013): 6233–37. http://dx.doi.org/10.1002/adma.201302737.

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Lachowicz, Dorota, Agnieszka Kaczyńska, Anna Bodzon-Kulakowska, Anna Karewicz, Roma Wirecka, Michał Szuwarzyński, and Szczepan Zapotoczny. "Coacervate Thermoresponsive Polysaccharide Nanoparticles as Delivery System for Piroxicam." International Journal of Molecular Sciences 21, no. 24 (December 18, 2020): 9664. http://dx.doi.org/10.3390/ijms21249664.

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Low water solubility frequently compromises the therapeutic efficacy of drugs and other biologically active molecules. Here, we report on coacervate polysaccharide nanoparticles (CPNs) that can transport and release a model hydrophobic drug, piroxicam, to the cells in response to changes in temperature. The proposed, temperature-responsive drug delivery system is based on ionic derivatives of natural polysaccharides—curdlan and hydroxypropyl cellulose. Curdlan was modified with trimethylammonium groups, while the anionic derivative of hydroxypropyl cellulose was obtained by the introduction of styrenesulfonate groups. Thermally responsive nanoparticles of spherical shape and average hydrodynamic diameter in the range of 250–300 nm were spontaneously formed in water from the obtained ionic polysaccharides as a result of the coacervation process. Their morphology was visualized using SEM and AFM. The size and the surface charge of the obtained objects could be tailored by adjusting the polycation/polyanion ratio. Piroxicam (PIX) was effectively entrapped inside the nanoparticles. The release profile of the drug from the CPNs-PIX was found to be temperature-dependent in the range relevant for biomedical applications.

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Liu, Chi Hsien, and Mei Shan Cheng. "Nanoparticles Composed by Oligochitosan and Polyethylenimine for Gene Delivery." Applied Mechanics and Materials 284-287 (January 2013): 418–22. http://dx.doi.org/10.4028/www.scientific.net/amm.284-287.418.

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Cationic carriers including polyethylenimine, liposomes, and chitosan have been used to transfer plasmid DNA in vitro by condensing anionic DNA. Here, oligochitosan (OC) was found to have capacity for in-vitro gene delivery in four cell lines. Plasmid containing green fluorescent protein (GFP) gene was used as a reporter gene. The transfection efficacy and cell viability of the transfection vehicles were analyzed by using a high-throughput image analyzer. We found that DNA polyplexes formed by high dosage of OC could be efficiently delivered into the cells. The combination of OC and polyethylenimine (PEI) were found to significantly enhance the fluorescence protein expression. The introduction of oligochitosan in PEI-mediated transfection could increase the transfection efficacy and could reduce the toxicity of PEI. Additionally, the synergistic effects of PEI and OC were confirmed in CHO, Caco2, Hep-SK, and 3T3 cell lines. The detailed mechanism of PEI and oligochitosan on transfection was investigated by using gel retardation and DNase degradation experiments. A facile and inexpensive construction of gene delivering vehicles was developed herein by using oligochitosan and PEI.

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Gupta, Anurag, Lalit N. Goswami, Manivannan Ethirajan, Joseph Missert, K. V. R. Rao, Tymish Ohulchanskyy, Indrajit Roy, Janet Morgan, Paras N. Prasad, and Ravindra K. Pandey. "Organically modified silica nanoparticles as drug delivery vehicles in photodynamic therapy." Journal of Porphyrins and Phthalocyanines 15, no. 05n06 (May 2011): 401–11. http://dx.doi.org/10.1142/s1088424611003306.

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To investigate the effect of hydrophobicity, charge and size of photosensitizers (PS) on their encapsulation efficiency in organically modified silica nanoparticles (ORMOSIL), a series of alkyl ether analogs of 2-(1′-hexyloxyethyl)-2-devinyl pyropheophorbide-a (HPPH) containing varied number of carbon units, HPPH with anionic and cationic functionalities, and HPPH analogs with molecular weight ranging from ~630 to 6000 Daltons were synthesized. Our preliminary results suggest that these factors play a significant role in encapsulation of the photosensitizers and their release from ORMOSIL nanoparticles. The synthesis and characterization of PS-encapsulated ORMOSIL and a comparative study on the effect of PS size, lipophilicity and charge on encapsulation efficiency, photophysical characteristics and release kinetics are discussed.

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Wang, Ming, John A. Zuris, Fantao Meng, Holly Rees, Shuo Sun, Pu Deng, Yong Han, et al. "Efficient delivery of genome-editing proteins using bioreducible lipid nanoparticles." Proceedings of the National Academy of Sciences 113, no. 11 (February 29, 2016): 2868–73. http://dx.doi.org/10.1073/pnas.1520244113.

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A central challenge to the development of protein-based therapeutics is the inefficiency of delivery of protein cargo across the mammalian cell membrane, including escape from endosomes. Here we report that combining bioreducible lipid nanoparticles with negatively supercharged Cre recombinase or anionic Cas9:single-guide (sg)RNA complexes drives the electrostatic assembly of nanoparticles that mediate potent protein delivery and genome editing. These bioreducible lipids efficiently deliver protein cargo into cells, facilitate the escape of protein from endosomes in response to the reductive intracellular environment, and direct protein to its intracellular target sites. The delivery of supercharged Cre protein and Cas9:sgRNA complexed with bioreducible lipids into cultured human cells enables gene recombination and genome editing with efficiencies greater than 70%. In addition, we demonstrate that these lipids are effective for functional protein delivery into mouse brain for gene recombination in vivo. Therefore, the integration of this bioreducible lipid platform with protein engineering has the potential to advance the therapeutic relevance of protein-based genome editing.

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Journal articles on the topic 'Cellular Delivery - Anionic Nanoparticles'

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