Kulhari Hitesh, Pooja Deep, Shrivastava Shweta, Telukutala Srinivasa R, Barui Ayan K, Patra Chitta Ranjan, Naidu Vegi Ganga Modi, Adams David J, Sistla Ramakrishna
IICT-RMIT Research Centre, CSIR-Indian Institute of Chemical Technology, Hyderabad, India; Medicinal Chemistry & Pharmacology Division, CSIR-Indian Institute of Chemical Technology, Hyderabad, India; School of Applied Sciences, RMIT University, Melbourne, Australia; Health Innovations Research Institute, RMIT University, Melbourne, Australia.
Medicinal Chemistry & Pharmacology Division, CSIR-Indian Institute of Chemical Technology, Hyderabad, India.
Nanomedicine. 2015 Aug;11(6):1511-20. doi: 10.1016/j.nano.2015.04.007. Epub 2015 Apr 29.
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.
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.
多西他赛（DTX）是一种抗癌药物，可单独使用或与其他药物联合用于治疗肿瘤。然而，它存在非特异性细胞毒性的缺点。为了提高DTX的治疗潜力，我们报道了合成用于靶向递送DTX的cRGDfK肽缀合的琥珀酰化TPGS（生育酚聚乙二醇琥珀酸酯）纳米胶束。在RGD（精氨酸-甘氨酸-天冬氨酸）肽中，cRGDfK肽对αvβ3整合素受体具有特异性，该受体在肿瘤细胞中最常过度表达。将琥珀酰化的TPGS合成并与cRGDfK肽使用碳二亚胺反应缀合。肽缀合的负载DTX的纳米胶束（PDNM）显示出粒径小且分布窄、药物释放可控且具有高物理化学稳定性。在DU145人前列腺癌细胞和人脐静脉内皮细胞（HUVECs）中，将未缀合的纳米胶束与PDNM进行细胞毒性、细胞摄取、凋亡和抗血管生成比较，清楚地揭示了cRGDfK肽在增强纳米胶束药物递送性能方面的重要性。
许多癌症化疗药物都存在一个共同问题，即全身毒性仍然是一个重大关注点。在本文中，作者试图通过将基于RGD的肽与多西他赛缀合来解决这个问题，这将靶向肿瘤细胞表面表达的整合素。实验数据显示药物递送得到了增强。
