期刊
POLYMER INTERNATIONAL
卷 62, 期 2, 页码 165-171出版社
WILEY
DOI: 10.1002/pi.4272
关键词
pullulan-doxorubicin conjugates; drug targeting; nanoparticle; multidrug resistance
资金
- National Nature Science Foundation of China [30770573, 30970788]
The goal of this study was to develop doxorubicin conjugate nanoparticles with increased antitumor effects, reduced side effects and the ability to overcome multidrug resistance (MDR). In this regard, folate-decorated maleilated pullulandoxorubicin conjugate nanoparticles were developed as carriers for co-delivery of pyrrolidinedithiocarbamate and doxorubicin (FA-MP-DOX/PDTC + DOX NPs). The resultant nanoparticles showed spherical geometry, with an average diameter of 152 nm. The two drugs were released from the nanoparticles in a slow, pH-dependent sustained release. To test the efficacy of these nanoparticles, in vitro tests including cell viability and folate receptor-mediated endocytosis were conducted against both A2780 cells and A2780/DOXR cells. Compared to free DOX, the FA-MP-DOX/PDTC + DOX NPs showed effective but less potent cytotoxicity against A2780 cells. For A2780/DOXR cells, they showed enhanced cellular uptake, increased targeting capacity and cytotoxicity. These results suggest that co-delivery of PDTC and DOX may further overcome MDR by transporting an increased amount of DOX within cells in addition to the folate receptor-mediated endocytosis process. (C) 2012 Society of Chemical Industry
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