Apoptotic cascade inspired lipid nanovesicles show synergism with encapsulated paclitaxel in chemoresistant colon carcinoma. (2014)

• Record Type: Journal Article
• Authors: Joshi, Nitin; Shanmugam, Thanigaivel; Deshmukh, Atul; Banerjee, Rinti
• Is Part Of: Nanomedicine. Volume 9:Number 12(2014)
• Page Start: 1789
• Page End: 1805
• Publication Date: 2014
• Subjects: colon carcinoma -- drug resistance -- lipid nanovesicles -- paclitaxel -- phosphatidylserine -- proapoptotic; Nanotechnology -- Periodicals; Medical technology -- Periodicals; Nanotechnology -- Therapeutic use -- Periodicals; 610.28
• DOI: 10.2217/nnm.13.182
• Languages: English
• ISSNs: 1743-5889

Abstract

Inspired from the apoptotic cascade, we developed phosphatidylserine (PS)-based proapoptotic lipid nanovesicles, capable of bypassing drug resistance and exhibiting synergistic anticancer activity with encapsulated paclitaxel in chemoresistant human colon adenocarcinoma (HCT-15).Materials & methods: Nanovesicles were developed and evaluated both in vitro and in vivo for their proapoptotic activity, synergism with encapsulated paclitaxel and ability to bypass drug resistance.Results: 110 ± 7 nm sized nanovesicles were found to be proapoptotic and synergistic with paclitaxel, and bypassed drug resistance. The formulation, with synergistic inputs from PS and paclitaxel, downregulated Ki-67 and inhibited angiogenesis leading to apoptosis by activating caspase-3 and downregulating Bcl-2, resulting in DNA fragmentation. The nanovesicles, while increasing the systemic circulation time of paclitaxel by 6.9-fold reduced systemic toxic effects of paclitaxel and were found to be nonimmunogenic.Conclusion: These results suggest the therapeutic potential of PS-based proapoptotic nanovesicles encapsulating paclitaxel in chemoresistant human colon carcinoma. Original submitted 8 January 2013; Revised submitted 6 September 2013