title: Enhanced antiproliferative and apoptosis effect of paclitaxel-loaded polymeric micelles against non-small cell lung cancers.
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.
authors.affiliation: National Hepatobiliary and Enteric Surgery Research Center, Ministry of Health, Xiangya Hospital, Central South University, No. 87 Xiangya Road, Changsha, Hunan, 410008, China.
authors.forename: Xiao-Ying
authors.initials: XY
authors.lastname: Zhang
authors.forename: Yang-De
authors.initials: YD
authors.lastname: Zhang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D016503:Drug Delivery Systems; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D006801:Humans; D051379:Mice; D008823:Micelles; D017239:Paclitaxel / Q000008:administration & dosage* / Q000737:chemistry; D011091:Polyesters / Q000008:administration & dosage* / Q000737:chemistry; D011092:Polyethylene Glycols / Q000008:administration & dosage* / Q000737:chemistry; D023041:Xenograft Model Antitumor Assays
chemical_list: D008823:Micelles; D011091:Polyesters; C439611:methoxy poly(ethylene glycol-co-epsilon-caprolactone); D011092:Polyethylene Glycols; D017239:Paclitaxel