Cyclic-RGDfK peptide conjugated succinoyl-TPGS nanomicelles for targeted delivery of docetaxel to integrin receptor over-expressing angiogenic tumours.

Abstract

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.

• Authors: Hitesh Kulhari, Deep Pooja, Shweta Shrivastava, Srinivasa R Telukutala, Ayan K Barui, Chitta Ranjan Patra, Ganga Modi Naidu Vegi, David J Adams, Ramakrishna Sistla
• Journal: Nanomedicine : nanotechnology, biology, and medicine (Nanomedicine) Vol. 11 Issue 6 Pg. 1511-20 (Aug 2015) ISSN: 1549-9642 [Electronic] United States
• PMID: 25933692 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 Elsevier Inc. All rights reserved.

Chemical References

• Antineoplastic Agents, Phytogenic
• Integrins
• Micelles
• Peptides, Cyclic
• Receptors, Cell Surface
• Taxoids
• cyclic (arginyl-glycyl-aspartyl-phenylalanyl-lysyl)
• Vitamin E
• Docetaxel
• Polyethylene Glycols
• tocophersolan

Topics

• Antineoplastic Agents, Phytogenic (administration & dosage)
• Cell Line, Tumor
• Docetaxel
• Human Umbilical Vein Endothelial Cells
• Humans
• Integrins (metabolism)
• Male
• Micelles
• Nanostructures
• Neovascularization, Pathologic
• Peptides, Cyclic (chemistry)
• Polyethylene Glycols (chemistry)
• Prostatic Neoplasms (blood supply, drug therapy, pathology)
• Receptors, Cell Surface (metabolism)
• Taxoids (administration & dosage)
• Vitamin E (analogs & derivatives, chemistry)