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Enhanced antiproliferative and apoptosis effect of paclitaxel-loaded polymeric micelles against non-small cell lung cancers

  • Research Article
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Tumor Biology

Abstract

Amphiphilic copolymer monomethoxy poly(ethylene glycol)-poly(caprolactone)-d-α-tocopheryl polyethylene glycol 1000 succinate (MPEG-PCL-TPGS) was prepared. In the present study, MPEG-PCL-TPGS was used as a novel nanovehicle for the delivery of paclitaxel (PTX) in the treatment of resistant lung cancers. The PTX-loaded MPEG-PCL-TPGS (PTX/MPT) micelles exhibited sustained release profile (168 h) with accelerated drug release at acidic pH conditions. The blank polymeric micelles showed excellent biocompatibility with cell viability of >85 %, making it suitable for all in vivo applications. PTX/MPT micelles displayed superior cytotoxicity in A-549 lung cancer cells than that of free PTX. The selective delivery of PTX to cancer cells resulted in enhanced cancer cell death. The PTX/MPT micelles showed higher cellular uptake via endocytosis pathways. The PTX-bound micelles preferentially arrested the cells at G2/M phase and showed a marked increase in sub G1 cell population (∼20 %). The pharmacokinetic study revealed a long blood circulation for PTX/MPT micelles. Finally, micellar formulation showed a remarkable tumor suppression effect in resistant A549/Taxol cells bearing xenograft nude mice along with no toxicity profile. The results indicate that the PTX-loaded biocompatible polymeric nanosystem could act as a potential delivery system for the treatment of lung carcinomas.

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Acknowledgment

The work was supported by the Ministry of Health, Xiangya Hospital Central South University, China.

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  1. National Hepatobiliary and Enteric Surgery Research Center, Ministry of Health, Xiangya Hospital, Central South University, No. 87 Xiangya Road, Changsha, Hunan, 410008, China

    Xiao-Ying Zhang & Yang-De Zhang

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  1. Xiao-Ying Zhang
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  2. Yang-De Zhang
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Correspondence to Yang-De Zhang.

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Zhang, XY., Zhang, YD. Enhanced antiproliferative and apoptosis effect of paclitaxel-loaded polymeric micelles against non-small cell lung cancers. Tumor Biol. 36, 4949–4959 (2015). https://doi.org/10.1007/s13277-015-3142-7

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  • DOI: https://doi.org/10.1007/s13277-015-3142-7

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