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Guan, Jiankun, Yuxin Wu, Huimin Wang, Haowen Zeng, Zifu Li i Xiangliang Yang. "A DiR loaded tumor targeting theranostic cisplatin-icodextrin prodrug nanoparticle for imaging guided chemo-photothermal cancer therapy". Nanoscale 13, nr 46 (2021): 19399–411. http://dx.doi.org/10.1039/d1nr05824j.
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A novel theranostic nanoplatform DPtFIP exhibited outstanding tumor targeting ability, imaging and photothermal properties, increased cellular uptake, selective drug release, and potent antitumor effect with decreased toxicity.
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Serda, Rita E., Natalie L. Adolphi, Marco Bisoffi i Laurel O. Sillerud. "Targeting and Cellular Trafficking of Magnetic Nanoparticles for Prostate Cancer Imaging". Molecular Imaging 6, nr 4 (1.07.2007): 7290.2007.00025. http://dx.doi.org/10.2310/7290.2007.00025.
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Antibody-conjugated iron oxide nanoparticles offer a specific and sensitive tool to enhance magnetic resonance (MR) images of both local and metastatic cancer. Prostate-specific membrane antigen (PSMA) is predominantly expressed on the neovasculature of solid tumors and on the surface of prostate cells, with enhanced expression following androgen deprivation therapy. Biotinylated anti-PSMA antibody was conjugated to streptavidin-labeled iron oxide nanoparticles and used in MR imaging and confocal laser scanning microscopic imaging studies using LNCaP prostate cancer cells. Labeled iron oxide nanoparticles are internalized by receptor-mediated endocytosis, which involves the formation of clathrin-coated vesicles. Endocytosed particles are not targeted to the Golgi apparatus for recycling but instead accumulate within lysosomes. In T1-weighted MR images, the signal enhancement owing to the magnetic particles was greater for cells with magnetic particles bound to the cell surface than for cells that internalized the particles. However, the location of the particles (surface vs internal) did not significantly alter their effect on T2-weighted images. Our findings indicate that targeting prostate cancer cells using PSMA offers a specific and sensitive technique for enhancing MR images.
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Jiang, Shan, Muthu Kumara Gnanasammandhan i Yong Zhang. "Optical imaging-guided cancer therapy with fluorescent nanoparticles". Journal of The Royal Society Interface 7, nr 42 (16.09.2009): 3–18. http://dx.doi.org/10.1098/rsif.2009.0243.
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The diagnosis and treatment of cancer have been greatly improved with the recent developments in nanotechnology. One of the promising nanoscale tools for cancer diagnosis is fluorescent nanoparticles (NPs), such as organic dye-doped NPs, quantum dots and upconversion NPs that enable highly sensitive optical imaging of cancer at cellular and animal level. Furthermore, the emerging development of novel multi-functional NPs, which can be conjugated with several functional molecules simultaneously including targeting moieties, therapeutic agents and imaging probes, provides new potentials for clinical therapies and diagnostics and undoubtedly will play a critical role in cancer therapy. In this article, we review the types and characteristics of fluorescent NPs, in vitro and in vivo imaging of cancer using fluorescent NPs and multi-functional NPs for imaging-guided cancer therapy.
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Santoso, Michelle R., i Phillip C. Yang. "Magnetic Nanoparticles for Targeting and Imaging of Stem Cells in Myocardial Infarction". Stem Cells International 2016 (2016): 1–9. http://dx.doi.org/10.1155/2016/4198790.
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Stem cell therapy has broad applications in regenerative medicine and increasingly within cardiovascular disease. Stem cells have emerged as a leading therapeutic option for many diseases and have broad applications in regenerative medicine. Injuries to the heart are often permanent due to the limited proliferation and self-healing capability of cardiomyocytes; as such, stem cell therapy has become increasingly important in the treatment of cardiovascular diseases. Despite extensive efforts to optimize cardiac stem cell therapy, challenges remain in the delivery and monitoring of cells injected into the myocardium. Other fields have successively used nanoscience and nanotechnology for a multitude of biomedical applications, including drug delivery, targeted imaging, hyperthermia, and tissue repair. In particular, superparamagnetic iron oxide nanoparticles (SPIONs) have been widely employed for molecular and cellular imaging. In this mini-review, we focus on the application of superparamagnetic iron oxide nanoparticles in targeting and monitoring of stem cells for the treatment of myocardial infarctions.
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Chen, Bin, Brian W. Pogue, P. Jack Hoopes i Tayyaba Hasan. "Combining vascular and cellular targeting regimens enhances the efficacy of photodynamic therapy". International Journal of Radiation Oncology*Biology*Physics 61, nr 4 (marzec 2005): 1216–26. http://dx.doi.org/10.1016/j.ijrobp.2004.08.006.
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Jin, Zhao-Hui, Atsushi B. Tsuji, Mélissa Degardin, Pascal Dumy, Didier Boturyn i Tatsuya Higashi. "Multiplexed Imaging Reveals the Spatial Relationship of the Extracellular Acidity-Targeting pHLIP with Necrosis, Hypoxia, and the Integrin-Targeting cRGD Peptide". Cells 11, nr 21 (4.11.2022): 3499. http://dx.doi.org/10.3390/cells11213499.
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pH (low) insertion peptides (pHLIPs) have been developed for cancer imaging and therapy targeting the acidic extracellular microenvironment. However, the characteristics of intratumoral distribution (ITD) of pHLIPs are not yet fully understood. This study aimed to reveal the details of the ITD of pHLIPs and their spatial relationship with other tumor features of concern. The fluorescent dye-labeled pHLIPs were intravenously administered to subcutaneous xenograft mouse models of U87MG and IGR-OV1 expressing αVβ3 integrins (using large necrotic tumors). The αVβ3 integrin-targeting Cy5.5-RAFT-c(-RGDfK-)4 was used as a reference. In vivo and ex vivo fluorescence imaging, whole-tumor section imaging, fluorescence microscopy, and multiplexed fluorescence colocalization analysis were performed. The ITD of fluorescent dye-labeled pHLIPs was heterogeneous, having a high degree of colocalization with necrosis. A direct one-to-one comparison of highly magnified images revealed the cellular localization of pHLIP in pyknotic, karyorrhexis, and karyolytic necrotic cells. pHLIP and hypoxia were spatially contiguous but not overlapping cellularly. The hypoxic region was found between the ITDs of pHLIP and the cRGD peptide and the Ki-67 proliferative activity remained detectable in the pHLIP-accumulated regions. The results provide a better understanding of the characteristics of ITD of pHLIPs, leading to new insights into the theranostic applications of pHLIPs.
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Liang, Zhiquan, Ziwen Lu, Yafei Zhang, Dongsheng Shang, Ruyan Li, Lanlan Liu, Zhicong Zhao i in. "Targeting Membrane Receptors of Ovarian Cancer Cells for Therapy". Current Cancer Drug Targets 19, nr 6 (21.06.2019): 449–67. http://dx.doi.org/10.2174/1568009618666181010091246.
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Ovarian cancer is a leading cause of death worldwide from gynecological malignancies, mainly because there are few early symptoms and the disease is generally diagnosed at an advanced stage. In addition, despite the effectiveness of cytoreductive surgery for ovarian cancer and the high response rates to chemotherapy, survival has improved little over the last 20 years. The management of patients with ovarian cancer also remains similar despite studies showing striking differences and heterogeneity among different subtypes. It is therefore clear that novel targeted therapeutics are urgently needed to improve clinical outcomes for ovarian cancer. To that end, several membrane receptors associated with pivotal cellular processes and often aberrantly overexpressed in ovarian cancer cells have emerged as potential targets for receptor-mediated therapeutic strategies including specific agents and multifunctional delivery systems based on ligand-receptor binding. This review focuses on the profiles and potentials of such strategies proposed for ovarian cancer treatment and imaging.
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Liu, Huiting, Xiaoqin Wang, Ran Yang, Wenbing Zeng, Dong Peng, Jason Li i Hu Wang. "Recent Development of Nuclear Molecular Imaging in Thyroid Cancer". BioMed Research International 2018 (2018): 1–10. http://dx.doi.org/10.1155/2018/2149532.
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Therapies targeting specific tumor pathways are easy to enter the clinic. To monitor molecular changes, cellular processes, and tumor microenvironment, molecular imaging is becoming the key technology for personalized medicine because of its high efficacy and low side effects. Thyroid cancer is the most common endocrine malignancy, and its theranostic radioiodine has been widely used to diagnose or treat differentiated thyroid cancer. This article summarizes recent development of molecular imaging in thyroid cancer, which may accelerate the development of personalized thyroid cancer therapy.
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Tanasova, Marina, Vagarshak V. Begoyan i Lukasz J. Weselinski. "Targeting Sugar Uptake and Metabolism for Cancer Identification and Therapy: An Overview". Current Topics in Medicinal Chemistry 18, nr 6 (28.06.2018): 467–83. http://dx.doi.org/10.2174/1568026618666180523110837.
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Metabolic deregulations have emerged as a cancer characteristic, opening a broad avenue for strategies and tools to target cancer through sugar uptake and metabolism. High expression levels of sugar transporters in cancer cells offered glycoconjugation as an approach to achieve enhanced cellular accumulation of drugs and imaging agents, with the sugar moiety anchoring the bioactive cargo to cancer cells. On the other hand, high demand for sugar nutrients in cancers provided a new avenue to target cancer cells with metabolic or sugar uptake inhibitors to induce cancer cells starvation or death. This overview summarizes recent advances in targeting cancer cells through sugar transport for cancer detection and therapy.
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Lalatonne, Y., M. Monteil, H. Jouni, J. M. Serfaty, O. Sainte-Catherine, N. Lièvre, S. Kusmia, P. Weinmann, M. Lecouvey i L. Motte. "Superparamagnetic Bifunctional Bisphosphonates Nanoparticles: A Potential MRI Contrast Agent for Osteoporosis Therapy and Diagnostic". Journal of Osteoporosis 2010 (2010): 1–7. http://dx.doi.org/10.4061/2010/747852.
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A bone targeting nanosystem is reported here which combined magnetic contrast agent for Magnetic Resonance Imaging (MRI) and a therapeutic agent (bisphosphonates) into one drug delivery system. This new targeting nanoplatform consists of superparamagneticγFe2O3nanoparticles conjugated to 1,5-dihydroxy-1,5,5-tris-phosphono-pentyl-phosphonic acid (di-HMBPs) molecules with a bisphosphonate function at the outer of the nanoparticle surface for bone targeting. The as-synthesized nanoparticles were evaluated as a specific MRI contrast agent by adsorption study onto hydroxyapatite and MRI measurment. The strong adsorption of the bisphosphonates nanoparticles to hydroxyapatite and their use as MRIT2∗contrast agent were demonstrated. Cellular tests performed on human osteosarcoma cells (MG63) show thatγFe2O3@di-HMBP hybrid nanomaterial has no citoxity effect in cell viability and may act as a diagnostic and therapeutic system.
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BOYES, STEPHEN G., MISTY D. ROWE, NATALIE J. SERKOVA, FERNANDO J. KIM, JAMES R. LAMBERT i PRIYA N. WERAHERA. "POLYMER-MODIFIED GADOLINIUM NANOPARTICLES FOR TARGETED MAGNETIC RESONANCE IMAGING AND THERAPY". Nano LIFE 01, nr 03n04 (wrzesień 2010): 263–75. http://dx.doi.org/10.1142/s1793984410000250.
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Functional imaging is a novel area in radiological sciences and allows for the non-invasive assessment and visualization of specific targets such as gene and protein expression, metabolic rates, and drug delivery in intact living subjects. As such, the field of molecular imaging has been defined as the non-invasive, quantitative, and repetitive imaging of biomolecules and biological processes in living organisms. For example, cancer cells may be genetically altered to attract molecules that alter the magnetic susceptibility, thereby permitting their identification by magnetic resonance imaging. These contrast agents and/or molecular reporters are seen as essential to the task of molecular medicine to increase both sensitivity and specificity of imaging. Therefore, there are five general principles which need to be fulfilled in order to conduct a successful in vivo molecular imaging study: (1) selection of appropriate cellular and subcellular targets; (2) development of suitable in vivo affinity ligands (molecular probes); (3) delivery of these probes to the target organ; (4) amplification strategies able to detect minimal target concentrations; and (5) development of imaging systems with high resolution. Although there has been a wide range of routes taken to incorporate both imaging agents and a disease-targeting moiety into diagnostic devices, arguably the most interesting of these routes employs the use of nanoparticles. Nanoscale diagnostic systems that incorporate molecular targeting agents and diagnostic imaging capabilities are emerging as the next-generation imaging agents and have the potential to dramatically improve the outcome of the imaging, diagnosis, and treatment of a wide range of diseases. The present review addresses chemical aspects in development of molecular probes based upon gadolinium nanoparticles and their potential role in translational clinical imaging and therapy.
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Allen, Kevin J. H., Mackenzie E. Malo, Rubin Jiao i Ekaterina Dadachova. "Targeting Melanin in Melanoma with Radionuclide Therapy". International Journal of Molecular Sciences 23, nr 17 (23.08.2022): 9520. http://dx.doi.org/10.3390/ijms23179520.
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Nearly 100,000 individuals are expected to be diagnosed with melanoma in the United States in 2022. Treatment options for late-stage metastatic disease up until the 2010s were few and offered only slight improvement to the overall survival. The introduction of B-RAF inhibitors and anti-CTLA4 and anti-PD-1/PD-L1 immunotherapies into standard of care brought measurable increases in the overall survival across all stages of melanoma. Despite the improvement in the survival statistics, patients treated with targeted therapies and immunotherapies are subject to very serious side effects, the development of drug resistance, and the high costs of treatment. This leaves room for the development of novel approaches as well as for the exploration of novel combination therapies for the treatment of metastatic melanoma. One such approach is targeting melanin pigment with radionuclide therapy. Advances in melanin-targeting radionuclide therapy of melanoma can be viewed from two spheres: (1) radioimmunotherapy (RIT) and (2) radiolabeled small molecules. The investigation of mechanisms of the action and efficacy of targeting melanin in melanoma treatment by RIT points to the involvement of the immune system such as complement dependent cytotoxicity. The combination of RIT with immunotherapy presents synergistic killing in mouse melanoma models. The field of radiolabeled small molecules is focused on radioiodinated compounds that have the ability to cross the cellular membranes to access intracellular melanin and can be applied in both therapy and imaging as theranostics. Clinical applications of targeting melanin with radionuclide therapies have produced encouraging results and clinical work is on-going. Continued work on targeting melanin with radionuclide therapy as a monotherapy, or possibly in combination with standard of care agents, has the potential to strengthen the current treatment options for melanoma patients.
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Sk, Ugir Hossain, i Chie Kojima. "Dendrimers for theranostic applications". Biomolecular Concepts 6, nr 3 (1.06.2015): 205–17. http://dx.doi.org/10.1515/bmc-2015-0012.
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AbstractRecently, there have been tremendous advances in the development of various nanotechnology-based platforms for diagnosis and therapy. These nanoplatforms, which include liposomes, micelles, polymers, and dendrimers, comprise highly integrated nanoparticles that provide multiple functions, such as targeting, imaging, and therapy. This review focuses on dendrimer-based nanocarriers that have recently been developed for ‘theranostics (or theragnosis)’, a combination of therapy and diagnostics. We discuss the in vitro and in vivo applications of these nanocarriers in strategies against diseases including cancer. We also explore the use of dendrimers as imaging agents for fluorescence imaging, magnetic resonance imaging, X-ray computed tomography, and nuclear medical imaging.
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HUANG, HUANG-CHIAO, JAMES RAMOS, TARAKA SAI PAVAN GRANDHI, THRIMOORTHY POTTA i KAUSHAL REGE. "GOLD NANOPARTICLES IN CANCER IMAGING AND THERAPEUTICS". Nano LIFE 01, nr 03n04 (wrzesień 2010): 289–307. http://dx.doi.org/10.1142/s1793984410000274.
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The use of nanomedicine in the war on cancer diseases has progressed significantly in the recent past. Liposomal- and albumin-based chemotherapeutic agents as well as tumor contrast agents (e.g. Gd-DTPA, ferumoxides) have received FDA approval for human clinical use, while many other agents are in different phases of pre-clinical investigation and clinical trials. Plasmonic gold nanoparticles hold great promise as potential theranostic devices for detection and ablation of cancer diseases. This review discusses recent progress in the imaging, photothermal therapy, and nucleic acid/drug delivery using gold nanoparticles (spheres, shells, rods, cages) in vitro and in vivo. Issues relating to toxicity, biocompatibility, biodistribution, cellular uptake, and targeting efficiency are also discussed.
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Thariat, Juliette, Samuel Valable, Carine Laurent, Siamak Haghdoost, Elodie A. Pérès, Myriam Bernaudin, François Sichel i in. "Hadrontherapy Interactions in Molecular and Cellular Biology". International Journal of Molecular Sciences 21, nr 1 (24.12.2019): 133. http://dx.doi.org/10.3390/ijms21010133.
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The resistance of cancer cells to radiotherapy is a major issue in the curative treatment of cancer patients. This resistance can be intrinsic or acquired after irradiation and has various definitions, depending on the endpoint that is chosen in assessing the response to radiation. This phenomenon might be strengthened by the radiosensitivity of surrounding healthy tissues. Sensitive organs near the tumor that is to be treated can be affected by direct irradiation or experience nontargeted reactions, leading to early or late effects that disrupt the quality of life of patients. For several decades, new modalities of irradiation that involve accelerated particles have been available, such as proton therapy and carbon therapy, raising the possibility of specifically targeting the tumor volume. The goal of this review is to examine the up-to-date radiobiological and clinical aspects of hadrontherapy, a discipline that is maturing, with promising applications. We first describe the physical and biological advantages of particles and their application in cancer treatment. The contribution of the microenvironment and surrounding healthy tissues to tumor radioresistance is then discussed, in relation to imaging and accurate visualization of potentially resistant hypoxic areas using dedicated markers, to identify patients and tumors that could benefit from hadrontherapy over conventional irradiation. Finally, we consider combined treatment strategies to improve the particle therapy of radioresistant cancers.
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Sharma, Anirudh, Erik Cressman, Anilchandra Attaluri, Dara L. Kraitchman i Robert Ivkov. "Current Challenges in Image-Guided Magnetic Hyperthermia Therapy for Liver Cancer". Nanomaterials 12, nr 16 (12.08.2022): 2768. http://dx.doi.org/10.3390/nano12162768.
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For patients diagnosed with advanced and unresectable hepatocellular carcinoma (HCC), liver transplantation remains the best option to extend life. Challenges with organ supply often preclude liver transplantation, making palliative non-surgical options the default front-line treatments for many patients. Even with imaging guidance, success following treatment remains inconsistent and below expectations, so new approaches are needed. Imaging-guided thermal therapy interventions have emerged as attractive procedures that offer individualized tumor targeting with the potential for the selective targeting of tumor nodules without impairing liver function. Furthermore, imaging-guided thermal therapy with added standard-of-care chemotherapies targeted to the liver tumor can directly reduce the overall dose and limit toxicities commonly seen with systemic administration. Effectiveness of non-ablative thermal therapy (hyperthermia) depends on the achieved thermal dose, defined as time-at-temperature, and leads to molecular dysfunction, cellular disruption, and eventual tissue destruction with vascular collapse. Hyperthermia therapy requires controlled heat transfer to the target either by in situ generation of the energy or its on-target conversion from an external radiative source. Magnetic hyperthermia (MHT) is a nanotechnology-based thermal therapy that exploits energy dissipation (heat) from the forced magnetic hysteresis of a magnetic colloid. MHT with magnetic nanoparticles (MNPs) and alternating magnetic fields (AMFs) requires the targeted deposition of MNPs into the tumor, followed by exposure of the region to an AMF. Emerging modalities such as magnetic particle imaging (MPI) offer additional prospects to develop fully integrated (theranostic) systems that are capable of providing diagnostic imaging, treatment planning, therapy execution, and post-treatment follow-up on a single platform. In this review, we focus on recent advances in image-guided MHT applications specific to liver cancer
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Adams, Lisa, Julia Brangsch, Bernd Hamm, Marcus R. Makowski i Sarah Keller. "Targeting the Extracellular Matrix in Abdominal Aortic Aneurysms Using Molecular Imaging Insights". International Journal of Molecular Sciences 22, nr 5 (7.03.2021): 2685. http://dx.doi.org/10.3390/ijms22052685.
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This review outlines recent preclinical and clinical advances in molecular imaging of abdominal aortic aneurysms (AAA) with a focus on molecular magnetic resonance imaging (MRI) of the extracellular matrix (ECM). In addition, developments in pharmacologic treatment of AAA targeting the ECM will be discussed and results from animal studies will be contrasted with clinical trials. Abdominal aortic aneurysm (AAA) is an often fatal disease without non-invasive pharmacologic treatment options. The ECM, with collagen type I and elastin as major components, is the key structural component of the aortic wall and is recognized as a target tissue for both initiation and the progression of AAA. Molecular imaging allows in vivo measurement and characterization of biological processes at the cellular and molecular level and sets forth to visualize molecular abnormalities at an early stage of disease, facilitating novel diagnostic and therapeutic pathways. By providing surrogate criteria for the in vivo evaluation of the effects of pharmacological therapies, molecular imaging techniques targeting the ECM can facilitate pharmacological drug development. In addition, molecular targets can also be used in theranostic approaches that have the potential for timely diagnosis and concurrent medical therapy. Recent successes in preclinical studies suggest future opportunities for clinical translation. However, further clinical studies are needed to validate the most promising molecular targets for human application.
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Dupont, Anne-Claire, Bérenger Largeau, Denis Guilloteau, Maria Joao Santiago Ribeiro i Nicolas Arlicot. "The Place of PET to Assess New Therapeutic Effectiveness in Neurodegenerative Diseases". Contrast Media & Molecular Imaging 2018 (2018): 1–15. http://dx.doi.org/10.1155/2018/7043578.
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In vivo exploration of neurodegenerative diseases by positron emission tomography (PET) imaging has matured over the last 20 years, using dedicated radiopharmaceuticals targeting cellular metabolism, neurotransmission, neuroinflammation, or abnormal protein aggregates (beta-amyloid and intracellular microtubule inclusions containing hyperphosphorylated tau). The ability of PET to characterize biological processes at the cellular and molecular levels enables early detection and identification of molecular mechanisms associated with disease progression, by providing accurate, reliable, and longitudinally reproducible quantitative biomarkers. Thus, PET imaging has become a relevant imaging method for monitoring response to therapy, approved as an outcome measure in bioclinical trials. The aim of this paper is to review and discuss the current inputs of PET in the assessment of therapeutic effectiveness in neurodegenerative diseases connected by common pathophysiological mechanisms, including Parkinson’s disease, Huntington’s disease, dementia, amyotrophic lateral sclerosis, multiple sclerosis, and also in psychiatric disorders. We also discuss opportunities for PET imaging to drive more personalized neuroprotective and therapeutic strategies, taking into account individual variability, within the growing framework of precision medicine.
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Vorobyeva, Anzhelika, Elena Konovalova, Tianqi Xu, Alexey Schulga, Mohamed Altai, Javad Garousi, Sara S. Rinne, Anna Orlova, Vladimir Tolmachev i Sergey Deyev. "Feasibility of Imaging EpCAM Expression in Ovarian Cancer Using Radiolabeled DARPin Ec1". International Journal of Molecular Sciences 21, nr 9 (7.05.2020): 3310. http://dx.doi.org/10.3390/ijms21093310.
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Epithelial cell adhesion molecule (EpCAM) is overexpressed in 55%–75% of ovarian carcinomas (OC). EpCAM might be used as a target for a treatment of disseminated OC. Designed ankyrin repeats protein (DARPin) Ec1 is a small (18 kDa) protein, which binds to EpCAM with subnanomolar affinity. We tested a hypothesis that Ec1 labeled with a non-residualizing label might serve as a companion imaging diagnostic for stratification of patients for EpCAM-targeting therapy. Ec1 was labeled with 125I using N-succinimidyl-para-iodobenzoate. Binding affinity, specificity, and cellular processing of [125I]I-PIB-Ec1 were evaluated using SKOV-3 and OVCAR-3 ovarian carcinoma cell lines. Biodistribution and tumor-targeting properties of [125I]I-PIB-Ec1 were studied in Balb/c nu/nu mice bearing SKOV-3 and OVCAR-3 xenografts. EpCAM-negative Ramos lymphoma xenografts served as specificity control. Binding of [125I]I-PIB-Ec1 to ovarian carcinoma cell lines was highly specific and had affinity in picomolar range. Slow internalization of [125I]I-PIB-Ec1 by OC cells confirmed utility of non-residualizing label for in vivo imaging. [125I]I-PIB-Ec1 provided 6 h after injection tumor-to-blood ratios of 30 ± 11 and 48 ± 12 for OVCAR-3 and SKOV-3 xenografts, respectively, and high contrast to other organs. Tumor targeting was highly specific. Saturation of tumor uptake at a high dose of Ec1 in SKOV-3 model provided a rationale for dose selection in further studies using therapeutic conjugates of Ec1 for targeted therapy. In conclusion, [125I]I-PIB-Ec1 is a promising agent for visualizing EpCAM expression in OC.
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Hernández-Pedro, Norma Y., Edgar Rangel-López, Roxana Magaña-Maldonado, Verónica Pérez de la Cruz, Abel Santamaría del Angel, Benjamín Pineda i Julio Sotelo. "Application of Nanoparticles on Diagnosis and Therapy in Gliomas". BioMed Research International 2013 (2013): 1–20. http://dx.doi.org/10.1155/2013/351031.
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Glioblastoma multiforme (GBM) is one of the most deadly diseases that affect humans, and it is characterized by high resistance to chemotherapy and radiotherapy. Its median survival is only fourteen months, and this dramatic prognosis has stilled without changes during the last two decades; consequently GBM remains as an unsolved clinical problem. Therefore, alternative diagnostic and therapeutic approaches are needed for gliomas. Nanoparticles represent an innovative tool in research and therapies in GBM due to their capacity of self-assembly, small size, increased stability, biocompatibility, tumor-specific targeting using antibodies or ligands, encapsulation and delivery of antineoplastic drugs, and increasing the contact surface between cells and nanomaterials. The active targeting of nanoparticles through conjugation with cell surface markers could enhance the efficacy of nanoparticles for delivering several agents into the tumoral area while significantly reducing toxicity in living systems. Nanoparticles can exploit some biological pathways to achieve specific delivery to cellular and intracellular targets, including transport across the blood-brain barrier, which many anticancer drugs cannot bypass. This review addresses the advancements of nanoparticles in drug delivery, imaging, diagnosis, and therapy in gliomas. The mechanisms of action, potential effects, and therapeutic results of these systems and their future applications in GBM are discussed.
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Liu, Bin, Wen Cao, Jin Cheng, Sisi Fan, Shaojun Pan, Lirui Wang, Jiaqi Niu i in. "Human natural killer cells for targeting delivery of gold nanostars and bimodal imaging directed photothermal/photodynamic therapy and immunotherapy". Cancer Biology & Medicine 16, nr 4 (15.11.2019): 756–70. http://dx.doi.org/10.20892/j.issn.2095-3941.2019.0112.
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Objective: To construct a novel nanoplatform GNS@CaCO3/Ce6-NK by loading the CaCO3-coated gold nanostars (GNSs) with Chlorin e6 molecules (Ce6) into human peripheral blood mononuclear cells (PBMCs)-derived NK cells for tumor targeted therapy. Methods: GNS@CaCO3/Ce6 nanoparticles were prepared and characterized by TEM and UV-vis. The cell surface markers and cytokines secretion of NK cells before and after loading the GNS@CaCO3/Ce6 nanoparticles were detected by Flow Cytometry (FCM) and ELISA. Effects of the GNS@CaCO3/Ce6-NK cells on A549 cancer cells was determined by FCM and CCK-8. Intracellular fluorescent signals of GNS@CaCO3/Ce6-NK cells were detected via Confocal laser scanning microscopic (CLSM) and FCM at different time points. Intracellular ROS generation of GNS@CaCO3/Ce6-NK cells under laser irradiation were examined by FCM. The distribution of GNS@CaCO3/Ce6-NK in A549 tumor-bearing mice were observed by fluorescence imaging and PA imaging. The combination therapy of GNS@CaCO3/Ce6-NK under laser irradiation were investigated on tumor-bearing mice. Results: The coated CaCO3 shell on the surface of GNSs exhibited prominent delivery and protection effect of Ce6 during the cellular uptake process. The as-prepared multifunctional GNS@CaCO3/Ce6-NK cells possessed bimodal functions of fluorescence imaging and photoacoustic imaging. The as-prepared multifunctional GNS@CaCO3/Ce6-NK cells could actively target tumor tissues with the enhanced photothermal/photodynamic therapy and immunotherapy. Conclusions: The GNS@CaCO3/Ce6-NK shows effective tumor-targeting ability and prominent therapeutic efficacy toward lung cancer A549 tumor-bearing mice. Through fully utilizing the features of GNSs and NK cells, this new nanoplatform provides a new synergistic strategy for enhanced photothermal/photodynamic therapy and immunotherapy in the field of anticancer development in the near future.
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Sundaram, Prabhavathi, i Heidi Abrahamse. "Phototherapy Combined with Carbon Nanomaterials (1D and 2D) and Their Applications in Cancer Therapy". Materials 13, nr 21 (28.10.2020): 4830. http://dx.doi.org/10.3390/ma13214830.
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Carbon-based materials have attracted research interest worldwide due to their physical and chemical properties and wide surface area, rendering them excellent carrier molecules. They are widely used in biological applications like antimicrobial activity, cancer diagnosis, bio-imaging, targeting, drug delivery, biosensors, tissue engineering, dental care, and skin care. Carbon-based nanomaterials like carbon nanotubes and graphene have drawn more attention in the field of phototherapy due to their unique properties such as thermal conductivity, large surface area, and electrical properties. Phototherapy is a promising next-generation therapeutic modality for many modern medical conditions that include cancer diagnosis, targeting, and treatment. Phototherapy involves the major administration of photosensitizers (PSs), which absorb light sources and emit reactive oxygen species under cellular environments. Several types of nontoxic PSs are functionalized on carbon-based nanomaterials and have numerous advantages in cancer therapy. In this review, we discuss the potential role and combined effect of phototherapy and carbon nanomaterials, the mechanism and functionalization of PSs on nanomaterials, and their promising advantages in cancer therapy.
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Paliwal, Shivani Rai, Rameshroo Kenwat, Sabyasachi Maiti i Rishi Paliwal. "Nanotheranostics for Cancer Therapy and Detection: State of the Art". Current Pharmaceutical Design 26, nr 42 (12.12.2020): 5503–17. http://dx.doi.org/10.2174/1381612826666201116120422.
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Nanotheranostics, an approach of combining both diagnosis and therapy, is one of the latest advances in cancer therapy particularly. Nanocarriers designed and derived from inorganic materials such as like gold nanoparticles, silica nanoparticles, magnetic nanoparticles and carbon nanotubes have been explored for tremendous applications in this area. Similarly, nanoparticles composed of some organic material alone or in combination with inorganic nano-cargos have been developed pre-clinically and possess excellent features desired. Photothermal therapy, MRI, simultaneous imaging and delivery, and combination chemotherapy with a diagnosis are a few of the known methods exploring cancer therapy and detection at organ/tissue/molecular/sub-cellular level. This review comprises an overview of the recent reports meant for nano theranostics purposes. Targeted cancer nanotheranostics have been included for understating tumor micro-environment or cell-specific targeting approach employed. A brief account of various strategies is also included for the readers highlighting the mechanism of cancer therapy.
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Koczorowski, Tomasz, Arleta Glowacka-Sobotta, Maciej Michalak, Dariusz T. Mlynarczyk, Emre Güzel, Tomasz Goslinski i Lukasz Sobotta. "Connections between Metallic Nanoparticles and Chlorin e6—An Overview of Physicochemical and Biological Properties and Prospective Medical Applications". Applied Sciences 13, nr 6 (20.03.2023): 3933. http://dx.doi.org/10.3390/app13063933.
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Photodynamic therapy is a non-invasive method of treatment for both neoplastic diseases and miscellaneous non-cancerous illnesses. It is complementary and, in some way, counter to various traditional treatment techniques, including chemotherapy, radiotherapy, and surgery. To date, various types of nanoparticles and compounds, including those belonging to the porphyrinoid group, have been researched in terms of future applications in technology and medicine. Among them, chlorins and their conjugates, combined with metallic nanoparticles, deserve special attention due to their enhanced photodynamic activity and the accompanied synergic photothermal effect. Many hybrid nanosystems reveal increased cellular uptake and improved stability and, therefore, can be applied in enhanced MRI imaging, as well as in targeting therapy. This review is focused on conjugates of metallic nanoparticles and chlorins, having in mind prospective applications as photosensitizers in multimodal neoplastic therapy, as well as tumor diagnosis.
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Liu, Yewei, Shuncong Wang, Xiaohui Zhao, Yuanbo Feng, Guy Bormans, Johan Swinnen, Raymond Oyen, Gang Huang, Yicheng Ni i Yue Li. "Predicting Clinical Efficacy of Vascular Disrupting Agents in Rodent Models of Primary and Secondary Liver Cancers: An Overview with Imaging-Histopathology Correlation". Diagnostics 10, nr 2 (31.01.2020): 78. http://dx.doi.org/10.3390/diagnostics10020078.
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Vascular disrupting agents (VDAs) have entered clinical trials for over 15 years. As the leading VDA, combretastatin A4 phosphate (CA4P) has been evaluated in combination with chemotherapy and molecular targeting agents among patients with ovarian cancer, lung cancer and thyroid cancer, but still remains rarely explored in human liver cancers. To overcome tumor residues and regrowth after CA4P monotherapy, a novel dual targeting pan-anticancer theragnostic strategy, i.e., OncoCiDia, has been developed and shown promise previously in secondary liver tumor models. Animal model of primary liver cancer is time consuming to induce, but of value for more closely mimicking human liver cancers in terms of tumor angiogenesis, histopathological heterogeneity, cellular differentiation, tumor components, cancer progression and therapeutic response. Being increasingly adopted in VDA researches, multiparametric magnetic resonance imaging (MRI) provides imaging biomarkers to reflect in vivo tumor responses to drugs. In this article as a chapter of a doctoral thesis, we overview the construction and clinical relevance of primary and secondary liver cancer models in rodents. Target selection for CA4P therapy assisted by enhanced MRI using hepatobiliary contrast agents (CAs), and therapeutic efficacy evaluated by using MRI with a non-specific contrast agent, dynamic contrast enhanced (DCE) imaging, diffusion weighted imaging (DWI) are also described. We then summarize diverse responses among primary hepatocellular carcinomas (HCCs), secondary liver and pancreatic tumors to CA4P, which appeared to be related to tumor size, vascularity, and cellular differentiation. In general, imaging-histopathology correlation studies allow to conclude that CA4P tends to be more effective in secondary liver tumors and in more differentiated HCCs, but less effective in less differentiated HCCs and implanted pancreatic tumor. Notably, cirrhotic liver may be responsive to CA4P as well. All these could be instructive for future clinical trials of VDAs.
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Oronova, Adelina, i Marina Tanasova. "Late-Stage Functionalization through Click Chemistry Provides GLUT5-Targeting Glycoconjugate as a Potential PET Imaging Probe". International Journal of Molecular Sciences 24, nr 1 (22.12.2022): 173. http://dx.doi.org/10.3390/ijms24010173.
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The targeting of facilitative sugar transporters (GLUTs) has been utilized in the development of tools for diagnostics and therapy. The interest in this area is promoted by the phenomenon of alterations in cellular metabolic processes that are linked to multitudes of metabolic disorders and diseases. However, nonspecific targeting (e.g., glucose-transporting GLUTs) leads to a lack of disease detection efficiency. Among GLUTs, GLUT5 stands out as a prominent target for developing specific molecular tools due to its association with metabolic diseases, including cancer. This work reports a non-radiolabeled fluoride (19F) coumarin-based glycoconjugate of 2,5-anhydro-D-mannitol as a potential PET imaging probe that targets the GLUT5 transporter. Inherent fluorescent properties of the coumarin fluorophore allowed us to establish the probe’s uptake efficiency and GLUT5-specificity in a GLUT5-positive breast cell line using fluorescence detection techniques. The click chemistry approach employed in the design of the probe enables late-stage functionalization, an essential requirement for obtaining the radiolabeled analog of the probe for future in vivo cancer imaging applications. The high affinity of the probe to GLUT5 allowed for the effective uptake in nutrition-rich media.
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Nicosia, Aldo, Gennara Cavallaro, Salvatore Costa, Mara Utzeri, Angela Cuttitta, Gaetano Giammona i Nicolò Mauro. "Carbon Nanodots for On Demand Chemophotothermal Therapy Combination to Elicit Necroptosis: Overcoming Apoptosis Resistance in Breast Cancer Cell Lines". Cancers 12, nr 11 (25.10.2020): 3114. http://dx.doi.org/10.3390/cancers12113114.
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Background: Engineered luminescent carbon nanodots (CDs) are appealing nanomaterials for cancer image-guided photothermal therapy combining near infrared (NIR)–triggered hyperthermia, imaging, and drug delivery in a single platform for efficient killing of cancer cells. This approach would allow eliciting synergistic regulated cell death (RCD) routes such as necroptosis, targeting breast cancer cells refractory to apoptosis, thus overcoming drug resistance. Methods: We report the preparation of CDs bearing biotin as a targeting agent (CDs-PEG-BT), which are able to load high amounts of irinotecan (23.7%) to be released in a pulsed on-demand fashion. CDs-PEG-BT have narrow size distribution, stable red luminescence, and high photothermal conversion in the NIR region, allowing imaging of MDA-MB231 and MCF-7 cancer cells and killing them by photothermal and chemotherapeutic insults. Results: Cellular uptake, viability profiles, and RCD gene expression analyses provided insights about the observed biocompatibility of CDs-PEG-BT, indicating that necroptosis can be induced on-demand after the photothermal activation. Besides, photothermal activation of drug-loaded CDs-PEG-BT implies both necroptosis and apoptosis by the TNFα and RIPK1 pathway. Conclusions: The controlled activation of necroptosis and apoptosis by combining phototherapy and on-demand release of irinotecan is the hallmark of efficient anticancer response in refractory breast cancer cell lines in view of precision medicine applications.
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Lu, Kai, Zheng Li, Qiang Hu, Jianfei Sun i Ming Chen. "CRPC Membrane-Camouflaged, Biomimetic Nanosystem for Overcoming Castration-Resistant Prostate Cancer by Cellular Vehicle-Aided Tumor Targeting". International Journal of Molecular Sciences 23, nr 7 (26.03.2022): 3623. http://dx.doi.org/10.3390/ijms23073623.
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Castration-resistant prostate cancer (CRPC) is the most common malignant tumor of the male urinary system. Nanodrug delivery systems (NDDS) have been widely applied in drug delivery for tumor therapy; however, nanotherapeutics encounter various biological barriers that prevent successful accumulation of drugs, specifically at diseased sites. Therefore, there is an urgent need to develop a CRPC-targeting nanocomposite with fine biocompatibility for penetrating various biological barriers, delivering sufficient drugs to the targeting site and improving therapeutic efficiency. In this work, CRPC cell membranes were firstly adapted as biomimetic vectors for the encapsulating PEG−PLGA polymer containing the chemotherapy drug docetaxel (DTX). The CRPC membrane-camouflaged nanoparticles can easily escape early recognition by the immune system, penetrate the extracellular barrier, and evade clearance by the circulatory system. In addition to the characteristics of traditional nanoparticles, the CRPC cell membrane contains an arsenal of highly specific homotypic moieties that can be used to recognize the same cancer cell types and increase the targeted drug delivery of DTX. In vivo fluorescence and radionuclide dual-model imaging were fulfilled by decorating the biomimetic nanosystem with near-infrared dye and isotope, which validated the homotypic targeting property offered by the CRPC cell membrane coating. Importantly, remarkably improved therapeutic efficacy was achieved in a mice model bearing CRPC tumors. This homologous cell membrane enabled an efficient drug delivery strategy and enlightened a new pathway for the clinical application of tumor chemotherapy drugs in the future.
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Humby, Frances, Myles Lewis, Nandhini Ramamoorthi, Jason A. Hackney, Michael R. Barnes, Michele Bombardieri, A. Francesca Setiadi i in. "Synovial cellular and molecular signatures stratify clinical response to csDMARD therapy and predict radiographic progression in early rheumatoid arthritis patients". Annals of the Rheumatic Diseases 78, nr 6 (16.03.2019): 761–72. http://dx.doi.org/10.1136/annrheumdis-2018-214539.
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ObjectivesTo unravel the hierarchy of cellular/molecular pathways in the disease tissue of early, treatment-naïve rheumatoid arthritis (RA) patients and determine their relationship with clinical phenotypes and treatment response/outcomes longitudinally.Methods144 consecutive treatment-naïve early RA patients (<12 months symptoms duration) underwent ultrasound-guided synovial biopsy before and 6 months after disease-modifying antirheumatic drug (DMARD) initiation. Synovial biopsies were analysed for cellular (immunohistology) and molecular (NanoString) characteristics and results compared with clinical and imaging outcomes. Differential gene expression analysis and logistic regression were applied to define variables correlating with treatment response and predicting radiographic progression.ResultsCellular and molecular analyses of synovial tissue demonstrated for the first time in early RA the presence of three pathology groups: (1) lympho-myeloid dominated by the presence of B cells in addition to myeloid cells; (2) diffuse-myeloid with myeloid lineage predominance but poor in B cells nd (3) pauci-immune characterised by scanty immune cells and prevalent stromal cells. Longitudinal correlation of molecular signatures demonstrated that elevation of myeloid- and lymphoid-associated gene expression strongly correlated with disease activity, acute phase reactants and DMARD response at 6 months. Furthermore, elevation of synovial lymphoid-associated genes correlated with autoantibody positivity and elevation of osteoclast-targeting genes predicting radiographic joint damage progression at 12 months. Patients with predominant pauci-immune pathology showed less severe disease activity and radiographic progression.ConclusionsWe demonstrate at disease presentation, prior to pathology modulation by therapy, the presence of specific cellular/molecular synovial signatures that delineate disease severity/progression and therapeutic response and may pave the way to more precise definition of RA taxonomy, therapeutic targeting and improved outcomes.
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Etrych, Tomáš, Olga Janoušková i Petr Chytil. "Fluorescence Imaging as a Tool in Preclinical Evaluation of Polymer-Based Nano-DDS Systems Intended for Cancer Treatment". Pharmaceutics 11, nr 9 (12.09.2019): 471. http://dx.doi.org/10.3390/pharmaceutics11090471.
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Targeted drug delivery using nano-sized carrier systems with targeting functions to malignant and inflammatory tissue and tailored controlled drug release inside targeted tissues or cells has been and is still intensively studied. A detailed understanding of the correlation between the pharmacokinetic properties and structure of the nano-sized carrier is crucial for the successful transition of targeted drug delivery nanomedicines into clinical practice. In preclinical research in particular, fluorescence imaging has become one of the most commonly used powerful imaging tools. Increasing numbers of suitable fluorescent dyes that are excitable in the visible to near-infrared (NIR) wavelengths of the spectrum and the non-invasive nature of the method have significantly expanded the applicability of fluorescence imaging. This chapter summarizes non-invasive fluorescence-based imaging methods and discusses their potential advantages and limitations in the field of drug delivery, especially in anticancer therapy. This chapter focuses on fluorescent imaging from the cellular level up to the highly sophisticated three-dimensional imaging modality at a systemic level. Moreover, we describe the possibility for simultaneous treatment and imaging using fluorescence theranostics and the combination of different imaging techniques, e.g., fluorescence imaging with computed tomography.
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Stan, Miruna-Silvia, Ionela Cristina Nica, Juliette Moreau, Maïté Callewaert, Cyril Cadiou, Françoise Chuburu, Hildegard Herman, Anca Hermenean, Anca Dinischiotu i Sorina N. Voicu. "Fluorescent Chitosan Nanogels Developed for Targeting Endothelial Cells of Axillary Lymph Nodes". Materials Proceedings 4, nr 1 (11.11.2020): 12. http://dx.doi.org/10.3390/iocn2020-07847.
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Nanogels are a novel class of three-dimensional cross-linked polymers able to retain high amounts of water in their network structure, with large potential applications in nanomedicine. In our study, the polymer matrix selected was chitosan, as this polysaccharide biopolymer composed of N-acetylglucosamine and glucosamine residues exhibits great biocompatibility and low toxicity. The preparation was performed by ionic gelation in the presence of hyaluronic acid and sodium tripolyphosphate, with rhodamine or fluorescein isothiocyanate molecules grafted on a chitosan backbone. In order to validate the possible usage of these chitosan-fluorophores conjugates for fluorescence imaging purposes in cancer diagnostics and therapy, their biological effect was assessed on SVEC4-10 cells (a simian virus 40-transformed mouse microvascular endothelial cell line). Cell viability, membrane integrity and nanogels uptake were examined following exposure for 6 and 24 h at concentrations up to 120 µg/mL. A good biocompatibility was obtained after both time intervals of incubation with nanogels, with no increase in cell death or membrane damage being noticed as compared to control. By examination on confocal laser scanning microscopy, both types of fluorescent nanogels agglomerated on the surface of the cell membrane, their cellular internalization being observed only for few cells, preferentially at the cell periphery. In conclusion, based on the biocompatibility of the nanogels, these can further incorporate gadolinium for an improved magnetic resonance imaging effect in nanomedicine.
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Wang, Hsin-Ta, Po-Chien Chou, Ping-Han Wu, Chi-Ming Lee, Kang-Hsin Fan, Wei-Jen Chang, Sheng-Yang Lee i Haw-Ming Huang. "Physical and Biological Evaluation of Low-Molecular-Weight Hyaluronic Acid/Fe3O4 Nanoparticle for Targeting MCF7 Breast Cancer Cells". Polymers 12, nr 5 (11.05.2020): 1094. http://dx.doi.org/10.3390/polym12051094.
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Low-molecular-weight hyaluronic acid (LMWHA) was integrated with superparamagnetic Fe3O4 nanoparticles (Fe3O4 NPs). The size distribution, zeta potential, viscosity, thermogravimetric and paramagnetic properties of the LMWHA-Fe3O4 NPs were systematically examined. For cellular experiments, MCF7 breast cancer cell line was carried out. In addition, the cell targeting ability and characteristics of the LMWHA-Fe3O4 NPs for MCF7 breast cancer cells were analyzed using the thiocyanate method and time-of-flight secondary ion mass spectrometry (TOF-SIMS). The experimental results showed that the LMWHA-Fe3O4 NPs were not only easily injectable due to their low viscosity, but also exhibited a significant superparamagnetic property. Furthermore, the in vitro assay results showed that the NPs had negligible cytotoxicity and exhibited a good cancer cell targeting ability. Overall, the results therefore suggest that the LMWHA-Fe3O4 NPs have considerable potential as an injectable agent for enhanced magnetic resonance imaging (MRI) and/or hyperthermia treatment in breast cancer therapy.
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von Spreckelsen, Niklas, Natalie Waldt, Rebecca Poetschke, Christoph Kesseler, Hildegard Dohmen, Hui-Ke Jiao, Attila Nemeth i in. "CBMT-25. THE KLF4K409Q MUTATION IN MENINGIOMA IMPAIRS HIF-1Α DEGRADATION AND CAN BE HARNESSED FOR TARGETED THERAPY". Neuro-Oncology 21, Supplement_6 (listopad 2019): vi38. http://dx.doi.org/10.1093/neuonc/noz175.147.
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Abstract Recently, several Non-NF2 driver mutations (KLF4, TRAF7, SMO, AKT1E17K) in meningioma have been identified. While they have been shown to correlate with certain pathological subtypes and locations, the clinical impact and repercussions on cellular pathways have largely remained elusive. Through analysis of clinical, pathological and preoperative imaging data of 96 patients and sequencing of the corresponding 96 tumor samples for the Krueppel like factor 4-K409Q mutation (KLF4K409Q) we present evidence that the KLF4K409Q tumors harbour an increased risk for peritumoral brain edema (PTBE) and can be predicted with the edema-index, a simple tool based on preoperative imaging. Further analysis involving RNA-sequencing of a matched subset of 7 KLF4K409Q and 10 KLF4-wildtype (wt) tumors revealed a significant shift of gene expression and the upregulation of hypoxia driven pathways, including VEGF levels, in KLF4K409Q tumors. On the cellular level, we go on to show that the KLF4K409Q mutation results in an increased KLF-4 stability as well as the inhibition of hydroxylation dependent degradation of HIF1-α and a significant increase of VEGF expression under hypoxic conditions. Finally, we demonstrate that this upregulation of VEGF in KLF4K409Q cells can be inhibited by targeting the mammalian target of rapamycin (mTor) with Temsirolimus. In summary we show that the KLF4K409Q mutation in meningioma has highly relevant repercussions in both, the biological and clinical context and can be harnessed for targeted therapy.
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Collado Camps, Estel, Sanne A. M. van Lith, Cathelijne Frielink, Jordi Lankhof, Ingrid Dijkgraaf, Martin Gotthardt i Roland Brock. "CPPs to the Test: Effects on Binding, Uptake and Biodistribution of a Tumor Targeting Nanobody". Pharmaceuticals 14, nr 7 (23.06.2021): 602. http://dx.doi.org/10.3390/ph14070602.
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Nanobodies are well-established targeting ligands for molecular imaging and therapy. Their short circulation time enables early imaging and reduces systemic radiation exposure. However, shorter circulation time leads to lower tracer accumulation in the target tissue. Cell-penetrating peptides (CPPs) improve cellular uptake of various cargoes, including nanobodies. CPPs could enhance tissue retention without compromising rapid clearance. However, systematic investigations on how the functionalities of nanobody and CPP combine with each other at the level of 2D and 3D cell cultures and in vivo are lacking. Here, we demonstrate that conjugates of the epidermal growth factor receptor (EGFR)-binding nanobody 7D12 with different CPPs (nonaarginine, penetratin, Tat and hLF) differ with respect to cell binding and induction of endocytosis. For nonaarginine and penetratin we compared the competition of EGF binding and performance of L- and D-peptide stereoisomers, and tested the D-peptide conjugates in tumor cell spheroids and in vivo. The D-peptide conjugates showed better penetration into spheroids than the unconjugated 7D12. Both in vivo and in vitro, the behavior of the agent reflects the combination of both functionalities. Although CPPs cause promising increases in in vitro uptake and 3D penetration, the dominant effect of the CPP in the control of biodistribution warrants further investigation.
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Grob, Nathalie M., Roger Schibli, Martin Béhé i Thomas L. Mindt. "Improved Tumor-Targeting with Peptidomimetic Analogs of Minigastrin 177Lu-PP-F11N". Cancers 13, nr 11 (27.05.2021): 2629. http://dx.doi.org/10.3390/cancers13112629.
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The cholecystokinin-2 receptor (CCK2R) is an attractive target in nuclear medicine due to its overexpression by different tumors. Several radiolabeled peptidic ligands targeting the CCK2R have been investigated in the past; however, their low stability against proteases can limit their uptake in tumors and metastases. Substitution of single or multiple amide bonds with metabolically stable 1,4-disubstituted 1,2,3-triazoles as amide bond bioisosteres proved a promising strategy for improving the tumor-targeting properties of a truncated analog of minigastrin. In this study, we applied the previously studied structural modifications to improve the pharmacokinetic and pharmacodynamic properties of PP-F11N, a minigastrin analog currently in clinical trials. Novel minigastrins (NMGs) as analogs of PP-F11N with one or two amide bonds substituted by 1,2,3-triazoles were synthesized, radiolabeled with 177Lu3+, and subjected to full evaluation in vitro (cell internalization, receptor affinity, stability in blood plasma) and in vivo (stability, biodistribution, SPECT/CT imaging). NMGs with triazoles inserted between the amino acids DGlu10-Ala11 and/or Tyr12-Gly13 showed a significantly increased cellular uptake and affinity toward the CCK2R in vitro. Resistance against the metabolic degradation of the NMGs was comparable to those of the clinical candidate PP-F11N. Imaging by SPECT/CT and biodistribution studies demonstrated a higher uptake in CCK2R-positive tumors but also in the CCK2R-positive stomach. The peptidomimetic compounds showed a slow tumor washout and high tumor-to-kidney ratios. The structural modifications led to the identification of analogs with promising properties for progression to clinical applications in the diagnosis and therapy of CCK2R-positive neoplasms.
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Pinto, Ricardo J. B., Nicole S. Lameirinhas, Gabriela Guedes, Gustavo H. Rodrigues da Silva, Párástu Oskoei, Stefan Spirk, Helena Oliveira, Iola F. Duarte, Carla Vilela i Carmen S. R. Freire. "Cellulose Nanocrystals/Chitosan-Based Nanosystems: Synthesis, Characterization, and Cellular Uptake on Breast Cancer Cells". Nanomaterials 11, nr 8 (12.08.2021): 2057. http://dx.doi.org/10.3390/nano11082057.
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Cellulose nanocrystals (CNCs) are elongated biobased nanostructures with unique characteristics that can be explored as nanosystems in cancer treatment. Herein, the synthesis, characterization, and cellular uptake on folate receptor (FR)-positive breast cancer cells of nanosystems based on CNCs and a chitosan (CS) derivative are investigated. The physical adsorption of the CS derivative, containing a targeting ligand (folic acid, FA) and an imaging agent (fluorescein isothiocyanate, FITC), on the surface of the CNCs was studied as an eco-friendly methodology to functionalize CNCs. The fluorescent CNCs/FA-CS-FITC nanosystems with a rod-like morphology showed good stability in simulated physiological and non-physiological conditions and non-cytotoxicity towards MDA-MB-231 breast cancer cells. These functionalized CNCs presented a concentration-dependent cellular internalization with a 5-fold increase in the fluorescence intensity for the nanosystem with the higher FA content. Furthermore, the exometabolic profile of the MDA-MB-231 cells exposed to the CNCs/FA-CS-FITC nanosystems disclosed a moderate impact on the cells’ metabolic activity, limited to decreased choline uptake and increased acetate release, which implies an anti-proliferative effect. The overall results demonstrate that the CNCs/FA-CS-FITC nanosystems, prepared by an eco-friendly approach, have a high affinity towards FR-positive cancer cells and thus might be applied as nanocarriers with imaging properties for active targeted therapy.
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Hallett, Robin M., Sarah E. Poplawski, Mark H. Dornan, Shin Hye Ahn, Shuang Pan, Wu Wengen, Liu Yuxin i in. "Abstract 3303: Pre-clinical characterization of the novel FAP targeting ligand PNT6555 for imaging and therapy of cancer". Cancer Research 82, nr 12_Supplement (15.06.2022): 3303. http://dx.doi.org/10.1158/1538-7445.am2022-3303.
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Abstract Background: Fibroblast Activation Protein-α (FAP) is a transmembrane glycoprotein highly expressed on activated fibroblasts. It is a constitutively active 170 kDa serine protease and a member of the dipeptide peptidase (DPP) family, sharing ~50% homology with DPPIV. FAP expression is only rarely expressed in normal adult tissues and is overexpressed in many epithelial cancers through upregulation on cancer-associated fibroblasts present in the stroma of various types of tumor. POINT BioPharma is developing PNT6555, which comprises a DOTA chelator linked to a FAP-targeting moiety, for imaging and therapeutic applications. Methods: PNT6555 and its radiometal chelates were evaluated for potency, selectivity, biodistribution and efficacy using biochemical and cellular assays as well as imaging, biodistribution and efficacy studies in tumor bearing mice. Results: PNT6555 and its gallium (natGa-PNT6555) and lutetium (natLu-PNT6555) chelates showed potent activity in FAP inhibition assays using human, mouse, and rat sources of FAP. PNT6555, natLu-PNT6555 and natGa-PNT6555 also showed significantly reduced potency when tested against PREP and DPPIV, two closely related homologous proteins. In vivo time-course biodistribution studies (by PET-imaging) with 68Ga-PNT6555 showed rapid clearance of 68Ga-PNT6555 from blood through the kidneys and urinary tract, with rising 68Ga-PNT6555 activity observed in the tumor through 60 minutes. At 60 minutes, the tumor was the only site of significant retained activity (>10 %ID/g). In vivo biodistribution studies (by SPECT imaging and direct organ assay) with 177Lu-PNT6555 showed rapid renal clearance into the bladder. After 24 hours, the tumor was the only tissue with significant activity retention. Direct organ assay showed little 177Lu-PNT6555 accumulation and retention in normal tissues with a high level of tumor retention observed out to 168h (>10 %ID/g). Therapeutic studies, using a single dose of 177Lu-PNT6555 or 225Ac-PNT6555, were completed in pre-clinical mouse models of cancer. In the HEK-mFAP model, significant dose responsive efficacy was observed in mice treated with either 177Lu-PNT6555 or 225Ac-PNT6555, with no apparent weight loss observed at all tested dose levels. Several mice experienced long-term survival >100 days at multiple of the tested dose levels. Conclusions: PNT6555, and its radiometal chelates, are potent and specific inhibitors of FAP. 68Ga/177Lu-PNT6555 showed rapid and prolonged uptake into FAP expressing tumors with limited uptake or retention observed in normal tissues. 177Lu/225Ac-PNT6555 showed compelling efficacy in pre-clinical tumor models that expressed FAP. Clinical studies with imaging and therapeutic chelates of PNT6555 are warranted. Citation Format: Robin M. Hallett, Sarah E. Poplawski, Mark H. Dornan, Shin Hye Ahn, Shuang Pan, Wu Wengen, Liu Yuxin, David G. Sanford, Valerie S. Hergott, Quang-De Nguyen, Anthony P. Belanger, Jack H. Lai, William Bachovchin, Joe A. McCann. Pre-clinical characterization of the novel FAP targeting ligand PNT6555 for imaging and therapy of cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3303.
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Krutzek, Fabian, Cornelius K. Donat, Martin Ullrich, Kristof Zarschler, Marie-Charlotte Ludik, Anja Feldmann, Liliana R. Loureiro, Klaus Kopka i Sven Stadlbauer. "Design and Biological Evaluation of Small-Molecule PET-Tracers for Imaging of Programmed Death Ligand 1". Cancers 15, nr 9 (6.05.2023): 2638. http://dx.doi.org/10.3390/cancers15092638.
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Noninvasive molecular imaging of the PD-1/PD-L1 immune checkpoint is of high clinical relevance for patient stratification and therapy monitoring in cancer patients. Here we report nine small-molecule PD-L1 radiotracers with solubilizing sulfonic acids and a linker–chelator system, designed by molecular docking experiments and synthesized according to a new, convergent synthetic strategy. Binding affinities were determined both in cellular saturation and real-time binding assay (LigandTracer), revealing dissociation constants in the single digit nanomolar range. Incubation in human serum and liver microsomes proved in vitro stability of these compounds. Small animal PET/CT imaging, in mice bearing PD-L1 overexpressing and PD-L1 negative tumors, showed moderate to low uptake. All compounds were cleared primarily through the hepatobiliary excretion route and showed a long circulation time. The latter was attributed to strong blood albumin binding effects, discovered during our binding experiments. Taken together, these compounds are a promising starting point for further development of a new class of PD-L1 targeting radiotracers.
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Lin, Yu-Wei, Hung-Cheng Su, Emmanuel Naveen Raj, Kuang-Kai Liu, Chien-Jen Chang, Tzu-Chia Hsu, Po-Yun Cheng i in. "Targeting EGFR and Monitoring Tumorigenesis of Human Lung Cancer Cells In Vitro and In Vivo Using Nanodiamond-Conjugated Specific EGFR Antibody". Pharmaceutics 15, nr 1 (28.12.2022): 111. http://dx.doi.org/10.3390/pharmaceutics15010111.
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Nanoprobes provide advantages for real-time monitoring of tumor markers and tumorigenesis during cancer progression and development. Epidermal growth factor receptor (EGFR) is a key protein that plays crucial roles for tumorigenesis and cancer therapy of lung cancers. Here, we show a carbon-based nanoprobe, nanodiamond (ND), which can be applied for targeting EGFR and monitoring tumorigenesis of human lung cancer cells in vitro and in vivo. The optimal fluorescent intensities of ND particles were observed in the human lung cancer cells and nude mice under in vivo imaging system. The fluorescence signal of ND particles can be real-time detected in the xenografted human lung tumor formation of nude mice. Moreover, the ND-conjugated specific EGFR antibody cetuximab (Cet) can track the location and distribution of EGFR proteins of lung cancer cells in vitro and in vivo. ND-Cet treatment increased cellular uptake ability of nanocomposites in the EGFR-expressed cells but not in the EGFR-negative lung cancer cells. Interestingly, single ND-Cet complex can be directly observed on the protein G bead by immunoprecipitation and confocal microscopy. Besides, the EGFR proteins were transported to lysosomes for degradation. Together, this study demonstrates that ND-conjugated Cet can apply for targeting EGFR and monitoring tumorigenesis during lung cancer progression and therapy.
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Puranik, Ameya D., Clarisse Dromain, Neil Fleshner, Mike Sathekge, Marianne Pavel, Nina Eberhardt, Friedemann Zengerling, Ralf Marienfeld, Michael Grunert i Vikas Prasad. "Target Heterogeneity in Oncology: The Best Predictor for Differential Response to Radioligand Therapy in Neuroendocrine Tumors and Prostate Cancer". Cancers 13, nr 14 (19.07.2021): 3607. http://dx.doi.org/10.3390/cancers13143607.
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Tumor or target heterogeneity (TH) implies presence of variable cellular populations having different genomic characteristics within the same tumor, or in different tumor sites of the same patient. The challenge is to identify this heterogeneity, as it has emerged as the most common cause of ‘treatment resistance’, to current therapeutic agents. We have focused our discussion on ‘Prostate Cancer’ and ‘Neuroendocrine Tumors’, and looked at the established methods for demonstrating heterogeneity, each with its advantages and drawbacks. Also, the available theranostic radiotracers targeting PSMA and somatostatin receptors combined with targeted systemic agents, have been described. Lu-177 labeled PSMA and DOTATATE are the ‘standard of care’ radionuclide therapeutic tracers for management of progressive treatment-resistant prostate cancer and NET. These approved therapies have shown reasonable benefit in treatment outcome, with improvement in quality of life parameters. Various biomarkers and predictors of response to radionuclide therapies targeting TH which are currently available and those which can be explored have been elaborated in details. Imaging-based features using artificial intelligence (AI) need to be developed to further predict the presence of TH. Also, novel theranostic tools binding to newer targets on surface of cancer cell should be explored to overcome the treatment resistance to current treatment regimens.
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Nguyen, Anh Thu, i Hee-Kwon Kim. "Recent Developments in PET and SPECT Radiotracers as Radiopharmaceuticals for Hypoxia Tumors". Pharmaceutics 15, nr 7 (27.06.2023): 1840. http://dx.doi.org/10.3390/pharmaceutics15071840.
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Hypoxia, a deficiency in the levels of oxygen, is a common feature of most solid tumors and induces many characteristics of cancer. Hypoxia is associated with metastases and strong resistance to radio- and chemotherapy, and can decrease the accuracy of cancer prognosis. Non-invasive imaging methods such as positron emission tomography (PET) and single-photon emission computed tomography (SPECT) using hypoxia-targeting radiopharmaceuticals have been used for the detection and therapy of tumor hypoxia. Nitroimidazoles are bioreducible moieties that can be selectively reduced under hypoxic conditions covalently bind to intracellular macromolecules, and are trapped within hypoxic cells and tissues. Recently, there has been a strong motivation to develop PET and SPECT radiotracers as radiopharmaceuticals containing nitroimidazole moieties for the visualization and treatment of hypoxic tumors. In this review, we summarize the development of some novel PET and SPECT radiotracers as radiopharmaceuticals containing nitroimidazoles, as well as their physicochemical properties, in vitro cellular uptake values, in vivo biodistribution, and PET/SPECT imaging results.
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Lundmark, Fanny, Gustav Olanders, Sara Sophie Rinne, Ayman Abouzayed, Anna Orlova i Ulrika Rosenström. "Design, Synthesis, and Evaluation of Linker-Optimised PSMA-Targeting Radioligands". Pharmaceutics 14, nr 5 (20.05.2022): 1098. http://dx.doi.org/10.3390/pharmaceutics14051098.
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Prostate-specific membrane antigen (PSMA) is overexpressed in the majority of prostate cancer cells and is considered to be an important target for the molecular imaging and therapy of prostate cancer. Herein, we present the design, synthesis, and evaluation of 11 PSMA-binding radioligands with modified linker structures, focusing on the relationship between molecular structure and targeting properties. The linker design was based on 2-naphthyl-L-alanine-tranexamic acid, the linker structure of PSMA-617. X-ray crystal-structure analysis of PSMA and structure-based design were used to generate the linker modifications, suggesting that substitution of tranexamic acid could lead to interactions with Phe546, Trp541, and Arg43 within the binding cavity. After synthesis through SPPS, analogues were labelled with indium-111 and evaluated in vitro for their specific binding, affinity, and cellular retention. Selected compounds were further evaluated in vivo in PSMA-expressing tumour-bearing mice. Based on the results, 2-naphthyl-L-alanine appears to be crucial for good targeting properties, whereas tranexamic acid could be replaced by other substituents. [111In]In-BQ7859, consisting of a 2-naphthyl-L-alanine-L-tyrosine linker, demonstrated favourable targeting properties. The substitution of tranexamic acid for L-tyrosine in the linker led to an improved tumour-to-blood ratio, highlighting [111In]In-BQ7859 as a promising PSMA-targeting radioligand.
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Liang, Hongda, Zheng Peng, Xiao Peng, Yufeng Yuan, Teng Ma, Yiwan Song, Jun Song i Junle Qu. "Fluorescence life-time imaging microscopy (FLIM) monitors tumor cell death triggered by photothermal therapy with MoS2 nanosheets". Journal of Innovative Optical Health Sciences 12, nr 05 (wrzesień 2019): 1940002. http://dx.doi.org/10.1142/s1793545819400029.
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Recently, photothermal therapy (PTT) has been proved to have great potential in tumor therapy. In the last several years, MoS2, as one novel member of nanomaterials, has been applied into PTT due to its excellent photothermal conversion efficacy. In this work, we applied fluorescence lifetime imaging microscopy (FLIM) techniques into monitoring the PPT-triggered cell death under MoS2 nanosheet treatment. Two types of MoS2 nanosheets (single layer nanosheets and few layer nanosheets) were obtained, both of which exhibited presentable photothermal conversion efficacy, leading to high cell death rates of 4T1 cells (mouse breast cancer cells) under PTT. Next, live cell images of 4T1 cells were obtained via directly labeling the mitochondria with Rodamine123, which were then continuously observed with FLIM technique. FLIM data showed that the fluorescence lifetimes of mitochondria targeting dye in cells treated with each type of MoS2 nanosheets significantly increased during PTT treatment. By contrast, the fluorescence lifetime of the same dye in control cells (without nanomaterials) remained constant after laser irradiation. These findings suggest that FLIM can be of great value in monitoring cell death process during PTT of cancer cells, which could provide dynamic data of the cellular microenvironment at single cell level in multiple biomedical applications.
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Chen, Kai, Xue Li, Hongyan Zhu, Qiyong Gong i Kui Luo. "Endocytosis of Nanoscale Systems for Cancer Treatments". Current Medicinal Chemistry 25, nr 25 (30.08.2018): 3017–35. http://dx.doi.org/10.2174/0929867324666170428153056.
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Advances in nanoscale systems for cancer treatment have been involved in enabling highly regulated site-specific localization to sub cellular organelles hidden beneath cell membranes. So far, the cellular entry of these nanoscale systems has not been fully understood. Endocytosis is an energy-dependent process of active transport in which elected extracellular molecules (such as proteins, viruses, micro-organisms and nanoscale systems) are engulfed into the cell. This process appears at the plasma membrane surface and contains internalization of the cell membrane as well as the membrane proteins and lipids of cell. There are multiform pathways of endocytosis for nanoscale systems. Further comprehension of the mechanisms of endocytosis is achieved with a combination of efficient genetic manipulations, cell dynamic imaging and chemical endocytosis inhibitors. This review provides an account of various endocytic pathways, itemizes current methods to study endocytosis of nanoscale systems, discusses some factors associated with cellular uptake for nanoscale systems and introduces the trafficking behavior for nanoscale systems with active targeting. An insight into the endocytosis mechanism is urgent and significant for developing safe and efficient nanoscale systems for cancer diagnosis and therapy.
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Chu, Charles C., Jonathan J. Pinney, Karl R. VanDerMeid, Raquel Izumi, Veerendra Munugalavadla, Paul M. Barr, Michael Rusty Elliott i Clive S. Zent. "Anti-CD20 Therapy Reliance on Antibody-Dependent Cellular Phagocytosis Affects Combination Drug Choice". Blood 134, Supplement_1 (13.11.2019): 682. http://dx.doi.org/10.1182/blood-2019-124901.
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The efficacy of many therapeutic unconjugated monoclonal antibodies (mAbs), including those targeting CD20 in CLL, requires immune cell-mediated cytotoxicity. mAbs have often been optimized for natural killer (NK) cell antibody-dependent cellular cytotoxicity (ADCC) activity. However, in vivo mouse studies have shown that antibody-dependent cellular phagocytosis (ADCP) by macrophages is the major mechanism of clearance of circulating B cells by anti-CD20 mAbs. To directly compare ADCC versus ADCP, we previously used a panel of anti-CD20 mAbs (rituximab, ofatumumab, obinutuzimab, ocaratuzumab) to test cytotoxicity of paired human NK cells and monocyte-derived macrophages (hMDM) against CLL cells in vitro. All mAbs demonstrated ADCP activity at least 10-fold greater than ADCC as measured by CLL cell depletion per effector cell. Moreover, ADCC and ADCP activity levels did not correlate, meaning that ADCC cannot be used as a surrogate measure of ADCP for these mAb. This could explain why mAb optimization for ADCC activity has often failed to translate into more efficacious treatment. Thus, ADCP may be an effective translational measurement of anti-CD20 mAb performance. Because of the clinical interest in combining anti-CD20 mAb with targeted small molecule inhibitors, we began studying the effects of the Bruton tyrosine kinase (BTK) inhibitors on anti-CD20 mAb-mediated ADCP. Our initial studies showed that ibrutinib (IBR), but not acalabrutinib (Acala), significantly decreased anti-CD20 ADCP as measured by a flow cytometry-based assay that measures single timepoint cell collections. These types of assays cannot easily determine the kinetics and individual effector cell activity of ADCP. Thus, to more fully study the BTK inhibitor effects on ADCP, we developed a live cell time-lapse imaging method for measuring ADCP, utilizing recent advances in microscopy, cellular dye labeling, digital imaging, imaging software and computing. Whole-cell labeling of macrophages enabled visualization of internalized CLL cells as regions of dye exclusion or "voids". Because of the vast number of images acquired during live cell time-lapse imaging, we utilized computer software-aided image recognition and enumeration to measure the number of macrophages and voids inside each macrophage. As a measure of phagocytic engulfment, we developed a void index, which provides a relative measure of phagocytic engulfment per macrophage. Measuring ADCP in this manner replicates clinical observation of mAb therapeutic activity. Clinically, intravenous anti-CD20 mAb therapy typically induces a rapid decrease in circulating CLL cells (within hours), followed by a long period (days) of stable to increased levels of circulating cells. Similarly, our live cell time-lapse video assay shows initial rapid ADCP over the first 2 hours followed by a prolonged period of "hypophagia" with little ADCP for the remainder of the assay (imaged every 2 minutes for 8 hours). This "hypophagia" phenomenon may explain the resistance to therapeutic mAb observed clinically. With these new tools for quantitation of ADCP, we compared the effects of serial dilutions of IBR or Acala on ADCP. Overall, as measured by Area Under the Curve (AUC) analysis, IBR decreased phagocytic capacity of anti-CD20 mediated CLL cell ADCP at concentrations of 0.41 μM and above. By contrast, Acala did not begin to decrease AUC measurements until 3.7 μM, and subsequent AUC values were higher in Acala versus IBR-treated ADCP assays up to the highest tested drug concentration (100 μM). Similarly, the initial ADCP kinetics (void index / min over the first hour) reflected a decrease with IBR treatment at 0.41 μM that continued until a nadir was reached at 33 μM. In contrast, Acala did not induce a decrease in this kinetic measurement until 3.7 μM and a nadir was not reached (up to 100 μM). Thus, IBR significantly decreases ADCP by hMDM at concentrations much lower than a more specific BTK inhibitor, Acala. This result suggests that BTK inhibition has little to no effect on ADCP and furthermore suggests that IBR off-target effects decrease ADCP. IBR off-target candidates include other tyrosine kinases in the TEC (tyrosine kinase expressed in hepatocellular carcinoma) family. These data suggest that a a highly selective BTK inhibitor with little effect on ADCP could be a more suitable drug to combine with therapeutic mAb(s). Disclosures Chu: Pfizer: Equity Ownership; Acerta Pharma: Research Funding. VanDerMeid:AstraZeneca: Research Funding. Izumi:Acerta Pharma: Employment, Equity Ownership, Patents & Royalties: Acalabrutinib patents; AstraZeneca: Equity Ownership. Munugalavadla:Acerta Pharma: Employment; AstraZeneca, Gilead Sciences: Equity Ownership. Barr:TG Therapeutics: Consultancy, Research Funding; Celgene: Consultancy; Pharmacyclics LLC, an AbbVie company: Consultancy, Research Funding; Seattle Genetics: Consultancy; Merck: Consultancy; Genentech: Consultancy; Verastem: Consultancy; Gilead: Consultancy; Astra Zeneca: Consultancy, Research Funding; Janssen: Consultancy; AbbVie: Consultancy. Elliott:Astra Zeneca: Research Funding. Zent:Mentrik Biotech: Research Funding; Astra Zeneca: Research Funding.
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Iravani, Siavash, i Rajender S. Varma. "MXenes in Cancer Nanotheranostics". Nanomaterials 12, nr 19 (27.09.2022): 3360. http://dx.doi.org/10.3390/nano12193360.
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MXenes encompass attractive properties such as a large surface area, unique chemical structures, stability, elastic mechanical strength, excellent electrical conductivity, hydrophilicity, and ease of surface functionalization/modifications, which make them one of the broadly explored two-dimensional materials in the world. MXene-based micro- and nanocomposites/systems with special optical, mechanical, electronic, and excellent targeting/selectivity features have been explored for cancer nanotheranostics. These materials exhibit great diagnostic and therapeutic potential and offer opportunities for cancer photoacoustic imaging along with photodynamic and photothermal therapy. They can be applied to targeted anticancer drug delivery while being deployed for the imaging/diagnosis of tumors/cancers and malignancies. MXene-based systems functionalized with suitable biocompatible or bioactive agents have suitable cellular uptake features with transferring potential from vascular endothelial cells and specific localization, high stability, and auto-fluorescence benefits at different emission–excitation wavelengths, permitting post-transport examination and tracking. The surface engineering of MXenes can improve their biocompatibility, targeting, bioavailability, and biodegradability along with their optical, mechanical, and electrochemical features to develop multifunctional systems with cancer theranostic applications. However, challenges still persist in terms of their environmentally benign fabrication, up-scalability, functionality improvement, optimization conditions, surface functionalization, biocompatibility, biodegradability, clinical translational studies, and pharmacokinetics. This manuscript delineates the recent advancements, opportunities, and important challenges pertaining to the cancer nanotheranostic potential of MXenes and their derivatives.
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Zhao, Linlin, Jongseon Choi, Yan Lu i So Yeon Kim. "NIR Photoregulated Theranostic System Based on Hexagonal-Phase Upconverting Nanoparticles for Tumor-Targeted Photodynamic Therapy and Fluorescence Imaging". Nanomaterials 10, nr 12 (25.11.2020): 2332. http://dx.doi.org/10.3390/nano10122332.
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Although photodynamic therapy (PDT) is an effective, minimally invasive therapeutic modality with advantages in highly localized and specific tumor treatments, large and deep-seated cancers within the body cannot be successfully treated due to low transparency to visible light. To improve the therapeutic efficiency of tumor treatment in deep tissue and reduce the side effects in normal tissue, this study developed a near-infrared (NIR)-triggered upconversion nanoparticle (UCNP)-based photosensitizer (PS) carrier as a new theranostics system. The NaYF4:Yb/Er UCNPs were synthesized by a hydrothermal method, producing nanoparticles of a uniformly small size (≈20 nm) and crystalline morphology of the hexagonal phase. These UCNPs were modified with folic acid-conjugated biocompatible block copolymers through a bidentate dihydrolipoic acid linker. The polymer modified hexagonal phase UCNPs (FA-PEAH-UCNPs) showed an improved dispersibility in the aqueous solution and strong NIR-to-vis upconversion fluorescence. The hydrophobic PS, pheophorbide a (Pha), was then conjugated to the stable vectors. Moreover, these UCNP-based Pha carriers containing tumor targeting folic acid ligands exhibited the significantly enhanced cellular uptake efficiency as well as PDT treatment efficiency. These results suggested that this system could extend the excitation wavelength of PDT to the NIR region and effectively improve therapeutic efficiency of PSs.
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Ncapayi, Vuyelwa, Neethu Ninan, Thabang C. Lebepe, Sundararajan Parani, Aswathy Ravindran Girija, Richard Bright, Krasimir Vasilev i in. "Diagnosis of Prostate Cancer and Prostatitis Using near Infra-Red Fluorescent AgInSe/ZnS Quantum Dots". International Journal of Molecular Sciences 22, nr 22 (19.11.2021): 12514. http://dx.doi.org/10.3390/ijms222212514.
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The link between the microbiome and cancer has led researchers to search for a potential probe for intracellular targeting of bacteria and cancer. Herein, we developed near infrared-emitting ternary AgInSe/ZnS quantum dots (QDs) for dual bacterial and cancer imaging. Briefly, water-soluble AgInSe/ZnS QDs were synthesized in a commercial kitchen pressure cooker. The as-synthesized QDs exhibited a spherical shape with a particle diameter of 4.5 ± 0.5 nm, and they were brightly fluorescent with a photoluminescence maximum at 705 nm. The QDs showed low toxicity against mouse mammary carcinoma (FM3A-Luc), mouse colon carcinoma (C26), malignant fibrous histiocytoma-like (KM-Luc/GFP) and prostate cancer cells, a greater number of accumulations in Staphylococcus aureus, and good cellular uptake in prostate cancer cells. This work is an excellent step towards using ternary QDs for diagnostic and guided therapy for prostate cancer.
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Shim, Hyunsuk, Alfredo Daniel Voloschin, Li Wei, Scott N. Hwang, Andrew H. Miller, Ying Guo, Daniel Brat i in. "Using proton MRSI to predict response to vorinostat treatment in recurrent GBM." Journal of Clinical Oncology 30, nr 15_suppl (20.05.2012): 3055. http://dx.doi.org/10.1200/jco.2012.30.15_suppl.3055.
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3055 Background: A major impediment to the development of new therapies for glioblastoma (GBM) is a lack of biomarkers indicating response. Epigenetic modifications are now recognized as a frequent occurrence in the early phases of tumorigenesis, playing a central role in tumor development. Epigenetic alterations differ significantly from genetic modifications in that they may be reversed by ‘‘epigenetic drugs’’ such as histone deacetylase inhibitors (HDACis). As a promising new modality for cancer therapy, the first generation of HDACi is currently being tested in phase I/II clinical trials. Methods: GBM alterations from therapy with HDACis, such as vorinostat (SAHA), include tumor redifferentiation/cytostasis rather than tumor size reduction limits the utility of traditional imaging methods such as MRI. Magnetic resonance spectroscopic imaging (MRSI) quantitates various metabolite levels in tumor and normal brain, allowing characterization of metabolic processes in live tissue. Results: In our preclinical model, MRS detected metabolic response to SAHA after only 3 days of treatment: reduced alanine and lactate and elevated myo-inositol, N-acetyl aspartate and creatine; each returning toward normal brain levels. This led to our clinical study of MRSI to evaluate the metabolic response of recurrent GBMs to SAHA + temozolomide. After only 7 days of SAHA treatment, MRSI can distinguish metabolic responders (normalization/restoration of tumor metabolites towards normal brain-like metabolism) from non-responders (no significant change in tumor metabolites). Our initial cohort (n=6) consists of 3 responders and 3 non-responders with highly significant differences in their change in metabolite levels (p < 0.001). Conclusions: Our results provide exciting insights into the mechanisms by which HDACi exerts its effect on GBMs. Tumor cells have increased biosynthetic needs requiring reprogramming of cellular metabolism. This creates increased energy demands, making tumor cells even more vulnerable to interventions targeting their metabolism. HDACi may induce redifferentiation in tumors by targeting tumor metabolism. Thus, MRSI provides a novel modality to predict response to HDACi-containing combination therapy in GBM.
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Hashempour Alamdari, Nasim, Mahmood Alaei-Beirami, Seyed Ataollah Sadat Shandiz, Hadi Hejazinia, Rahimeh Rasouli, Mostafa Saffari, Seyed Esmaeil Sadat Ebrahimi, Artin Assadi i Mehdi Shafiee Ardestani. "Gd3+-Asparagine-Anionic Linear Globular Dendrimer Second-Generation G2 Complexes: Novel Nanobiohybrid Theranostics". Contrast Media & Molecular Imaging 2017 (2017): 1–19. http://dx.doi.org/10.1155/2017/3625729.
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Designing a unique theranostic biocompatible, biodegradable, and cost-effective agent which is easy to be synthesized as a biohybrid material was the aim of this study. In this matter, asparagine attached to anionic linear globular dendrimer G2 (as a biocompatible, biodegradable, and cost-effective agent which is negatively charged nanosized and water soluble polymer that outweighs other traditionally used dendrimers) and finally contrast agent (Gd3+) was loaded (which made complexes) in synthesized asparagine-dendrimer. Observations revealed that, in addition to successful colon cancer and brain targeting, Gd3+-dendrimer-asparagine, the proposed theranostic agent, could increase T1 MR relaxation times, decrease T2 MR relaxation times significantly, and improve contrast of image as well as illustrating good cellular uptake based on florescent microscopy/flow cytometry and ICP-mass data. In addition to that, it increased tumor growth inhibition percentage (TGI%) significantly compared to FDA approved contrast agent, Magnevist. Totally, Gd3+-anionic linear globular dendrimer G2-asparagine could be introduced to the cancer imaging/therapy (theranostics) protocols after in vivo MR and fluorescent analysis and passing clinical trials. Hence, this nanotheranostic agent would be a promising candidate for brain drug delivery and imaging in the future.