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ACS Appl Mater Interfaces. 2014 Jun 11;6(11):8549-59. doi: 10.1021/am501422r. Epub 2014 May 7.

Thermo-triggered drug release from actively targeting polymer micelles.

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Key Laboratory of Advanced Technologies of Materials, Ministry of Education, School of Materials Science and Engineering, Southwest Jiaotong University , Chengdu 610031, China.


How to deliver the drug to the target area at the right time and at the right concentration is still a challenge in cancer therapy. In this study, we present a facile strategy to control drug release by precisely controlling the thermo-sensitivity of the nanocarriers to the variation of environmental temperature. One type of thermoresponsive Pluronic F127-poly(d,l-lactic acid) (F127-PLA, abbreviated as FP) copolymer micelles was developed and decorated with folate (FA) for active targeting. FP100 micelles assembled from FP with PLA segment having polymerization degree of 100 had a low critical solution temperature of 39.2 °C close to body temperature. At 37 °C, little amount of encapsulated anticancer drug DOX is released from the FP100 micelles, while at a slightly elevated temperature (40 °C), the shrinkage of thermoresponsive segments causes a rapid release of DOX and instantly increases the drug concentration locally. The cytocompatibility analysis and cellular uptake efficiency were characterized with the fibroblast cell line NIH 3T3 and human cervix adenocarcinoma cell line HeLa. The results demonstrate that this copolymer has excellent cytocompatibility, and FA-decorated FP100 micelles present much better efficiency of cellular uptake and higher cytotoxicity to folate receptor (FR)-overexpressed HeLa cells. In particular, under hyperthermia (40 °C) the cytotoxicity of DOX-loaded FA-FP100 micelles against HeLa cells was significantly more obvious than that upon normothermia (37 °C). Therefore, these temperature-responsive micelles have great potential as a drug vehicle for cancer therapy.

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