Self-assembled nanoparticles from folate-decorated maleilated pullulan–doxorubicin conjugate for improved drug delivery to cancer cells

Authors

  • Fei Li,

    1. Department of Pharmaceutical Analysis and Pharmaceutical Chemistry, School of Pharmacy, Fourth Military Medical University, Xi'an 710032, China
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  • Haitao Zhang,

    1. Department of Pharmaceutical Analysis and Pharmaceutical Chemistry, School of Pharmacy, Fourth Military Medical University, Xi'an 710032, China
    2. Department of Applied Chemistry, School of Science, Northwestern Polytechnical University, Xi'an 710072, China
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  • Chunhu Gu,

    1. Department of Cardiovascular Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China
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  • Li Fan,

    1. Department of Pharmaceutical Analysis and Pharmaceutical Chemistry, School of Pharmacy, Fourth Military Medical University, Xi'an 710032, China
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  • Youbei Qiao,

    1. Department of Pharmaceutical Analysis and Pharmaceutical Chemistry, School of Pharmacy, Fourth Military Medical University, Xi'an 710032, China
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  • Yangchun Tao,

    1. Department of Pharmaceutical Analysis and Pharmaceutical Chemistry, School of Pharmacy, Fourth Military Medical University, Xi'an 710032, China
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  • Chong Cheng,

    1. Department of Pharmaceutical Analysis and Pharmaceutical Chemistry, School of Pharmacy, Fourth Military Medical University, Xi'an 710032, China
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  • Hong Wu,

    Corresponding author
    • Department of Pharmaceutical Analysis and Pharmaceutical Chemistry, School of Pharmacy, Fourth Military Medical University, Xi'an 710032, China
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  • Jun Yi

    Corresponding author
    • Department of General Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China
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Correspondence to: Hong Wu, Department of Pharmaceutical Analysis and Pharmaceutical Chemistry, School of Pharmacy, Fourth Military Medical University, Xi'an 710032, China. E-mail: hongwuxa@hotmail.com

Jun Yi, Department of General Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China. E-mail: yijun@fmmu.edu.cn

Abstract

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 pullulan–doxorubicin 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. © 2012 Society of Chemical Industry

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