Theranostic vitamin E TPGS micelles of transferrin conjugation for targeted co-delivery of docetaxel and ultra bright gold nanoclusters |
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| Institution: | 1. Department of Chemical & Biomolecular Engineering, National University of Singapore, 4 Engineering Drive 4, Singapore 117585, Singapore;2. Department of Pharmacology, Institute of Medical Sciences, Banaras Hindu University, Varanasi 221005, India;3. International Joint Cancer Institute, The Second Military Medical University, 800 Xiang Yin Road, Shanghai 200433, China;1. State Key Laboratory of Natural Medicines and Jiangsu Key Laboratory of Drug Discovery for Metabolic Diseases, Center of Drug Discovery, China Pharmaceutical University, Nanjing 210009, China;2. UFR Pharmacie, Faculté des Sciences de la Santé, Université d''Abomey-Calavi, 01 BP 188 Cotonou, Benin;3. Jiangsu Key Laboratory of Drug Screening, China Pharmaceutical University, Nanjing 210009, China;4. Faculty of Pharmacy and Pharmaceutical Sciences, Monash University, Parkville, VIC 3052, Australia;1. State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau 999078, China;2. State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China;3. Department of Pediatrics, College of Medicine, University of FL, Gainesville, FL 32610, USA;1. Department of Bioengineering, National University of Singapore, Block EA, 03-12, 9 Engineering Drive 1, Singapore 117575, Singapore;2. Department of Chemical & Biomolecular Engineering, National University of Singapore, Block E5, 02-11, 4 Engineering Drive 4, Singapore 117576, Singapore;3. NanoCore, National University of Singapore, Block EA, 04-27, 9 Engineering Drive 1, Singapore 117576, Singapore;1. Department of Pharmacy, Guangdong Pharmaceutical University, Higher Education Mega Center, Guangzhou 510006, China;2. Department of Pharmacy, Guangdong Women and Children Hospital, Guangzhou 510006, China;3. Department of Pharmacy, Guangdong General Hospital, Guangdong Academy of Medical Sciences, 106 Zhongshan Second Road, Guangzhou 510080, China;4. Department of Pharmacy, The Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510006, China;1. Departamento de Tecnología Farmacéutica, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Argentina;2. Departamento de Farmacología, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Argentina;3. National Science Research Council (CONICET), Buenos Aires, Argentina;1. Department of Pneumology, The First People’s Hospital of Wenling, The Affiliated Wenling Hospital of Wenzhou Medical University, Taizhou, Zhejiang Province, 317500, PR China;2. Department of Emergency, Taizhou Hospital of Zhejiang Province, Taizhou, Zhejiang Province, 317500, PR China;3. Department of Emergency, The First People’s Hospital of Wenling, The Affiliated Wenling Hospital of Wenzhou Medical University, Taizhou, Zhejiang Province, 317500, PR China |
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| Abstract: | The aim of this work was to develop an advanced theranostic micelles of D-alpha-tocopheryl polyethylene glycol 1000 succinate (TPGS), which are conjugated with transferrin for targeted co-delivery of docetaxel (DTX) as a model drug and ultra bright gold clusters (AuNC) as a model imaging agent for simultaneous cancer imaging and therapy. The theranostic micelles with and without transferrin conjugation were prepared by the solvent casting method and characterized for their particle size, polydispersity, surface chemistry, drug encapsulation efficiency, drug loading and cellular uptake efficiency. Transferrin receptors expressing MDA-MB-231-luc breast cancer cells and NIH-3T3 fibroblast cells (control cells without transferrin receptor expression) were employed as an in vitro model to access cytotoxicity of the formulations. The overexpression of transferrin receptor on the surface of MDA-MB-231-luc cells was confirmed by flow cytometry. The biodistribution study and theranostic efficacy of the micelles were investigated by using the Xenogen IVIS® Spectrum imaging system, which includes AuNC based fluorescence imaging and luciferase induced bioluminescence imaging on MDA-MB-231-luc tumor bearing SCID mice. The IC50 values demonstrated that the non-targeted and targeted micelles could be 15.31 and 71.73 folds more effective than Taxotere® after 24 h treatment with the MDA-MB-231-luc cells. Transferrin receptor targeted delivery of such micelles was imaged in xenograft model and showed their great advantages for real-time tumor imaging and inhibition of tumor growth. |
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| Keywords: | Cancer nanotechnology Diagnostic imaging Gold nanoclusters Molecular biomaterials Nanomedicine Nanotheranostics |
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