Cyclic-RGDfK peptide conjugated succinoyl-TPGS nanomicelles for targeted delivery of docetaxel to integrin receptor over-expressing angiogenic tumours.
UNLABELLED
Docetaxel (DTX) is an anticancer drug that is used alone and in combination with other drugs to treat tumours. However, it suffers from the drawback of non-specific cytotoxicity. To improve the therapeutic potential of DTX, we report the synthesis of cRGDfK peptide-conjugated succinoyl-TPGS (tocopheryl polyethylene glycol succinate) nanomicelles for targeted delivery of DTX. Among RGD (Arg-Gly-Asp) peptides, cRGDfK peptide shows specificity towards αvβ3 integrin receptors that are most commonly over-expressed in tumour cells. To cRGDfK peptide, succinoylated TPGS was synthesised and conjugated to cRGDfK peptide using a carbodiimide reaction. Peptide-conjugated DTX loaded nanomicelles (PDNM) displayed small particle size with a narrow distribution, controlled drug release and high physicochemical stability. Cytotoxicity, cellular uptake, apoptosis and anti-angiogenic comparisons of unconjugated nanomicelles to PDNM in DU145 human prostate cancer cells and HUVECs (Human Umblical Vein Endothelial Cells) clearly revealed the importance of the cRGDfK peptide in enhancing the drug delivery performance of nanomicelles.


FROM THE CLINICAL EDITOR
Common to many chemotherapeutic agents for cancer, systemic toxicity remains a big concern. In this article, the authors attempted to address this issue by conjugating RGD based peptides to Docetaxel, which would target integrins expressed on tumor cell surface. The experimental data revealed enhanced drug delivery.
['Kulhari|Hitesh|H|', 'Pooja|Deep|D|', 'Shrivastava|Shweta|S|', 'Telukutala|Srinivasa R|SR|', 'Barui|Ayan K|AK|', 'Patra|Chitta Ranjan|CR|', 'Naidu Vegi|Ganga Modi|GM|', 'Adams|David J|DJ|', 'Sistla|Ramakrishna|R|']
D000972:Antineoplastic Agents, Phytogenic D045744:Cell Line, Tumor D000077143:Docetaxel D061307:Human Umbilical Vein Endothelial Cells D006801:Humans D016023:Integrins D008297:Male D008823:Micelles D049329:Nanostructures D009389:Neovascularization, Pathologic D010456:Peptides, Cyclic D011092:Polyethylene Glycols D011471:Prostatic Neoplasms D011956:Receptors, Cell Surface D043823:Taxoids D014810:Vitamin E
Nanomicelles Docetaxel Cytotoxicity cRGDfK TPGS Prostate cancer targeting