Theranostic vitamin E TPGS micelles of transferrin conjugation for targeted co-delivery of docetaxel and ultra bright gold nanoclusters

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 ag...

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Bibliographic Details
Published in:Biomaterials 2015-01, Vol.39, p.234-248
Main Authors: Muthu, Madaswamy S, Kutty, Rajaletchumy Veloo, Luo, Zhentao, Xie, Jianping, Feng, Si-Shen
Format: Article
Language:English
Subjects:
Advanced Basic Science
Animals
Breast Neoplasms
Cancer
Cancer nanotechnology
Cell Line
Conjugation
Dentistry
Diagnostic imaging
Drug Carriers - chemistry
Drugs
Flow Cytometry
Gold - chemistry
Gold nanoclusters
Humans
Imaging
Metal Nanoparticles - chemistry
Mice
Mice, SCID
Micelles
Microscopy, Electron, Transmission
Molecular biomaterials
Nanomedicine
Nanotheranostics
NIH 3T3 Cells
Particle Size
Polyethylene Glycols - chemistry
Receptors
Taxoids - administration & dosage
Taxoids - chemistry
Transferrin
Transferrin - chemistry
Tumors
Vitamin E - analogs & derivatives
Vitamin E - chemistry
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Summary: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.
ISSN:0142-9612
1878-5905
DOI:10.1016/j.biomaterials.2014.11.008