期刊
NANOMEDICINE
卷 9, 期 12, 页码 1789-1805出版社
FUTURE MEDICINE LTD
DOI: 10.2217/NNM.13.182
关键词
colon carcinoma; drug resistance; lipid nanovesicles; paclitaxel; phosphatidylserine; proapoptotic
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.
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