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A Strategy in The Design of Micellar Shape for Cancer Therapy

Authors

  • Tao Chen,

    1. School of Materials Science and Engineering, Key Laboratory of Advanced Technologies of Materials, Ministry of Education, Southwest Jiaotong University, Chengdu, 610031, P. R. China
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  • Xing Guo,

    1. School of Materials Science and Engineering, Key Laboratory of Advanced Technologies of Materials, Ministry of Education, Southwest Jiaotong University, Chengdu, 610031, P. R. China
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  • Xian Liu,

    1. School of Materials Science and Engineering, Key Laboratory of Advanced Technologies of Materials, Ministry of Education, Southwest Jiaotong University, Chengdu, 610031, P. R. China
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  • Shuai Shi,

    1. State Key Laboratory of Biotherapy, West China Hospital, West China Medicine School, Sichuan University, Chengdu, 610041, P. R. China
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  • Jie Wang,

    1. School of Materials Science and Engineering, Key Laboratory of Advanced Technologies of Materials, Ministry of Education, Southwest Jiaotong University, Chengdu, 610031, P. R. China
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  • Chunli Shi,

    1. School of Life Science and Engineering, Southwest Jiaotong University, Chengdu 610031, Sichuan, P.R. China
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  • Zhiyong Qian,

    1. State Key Laboratory of Biotherapy, West China Hospital, West China Medicine School, Sichuan University, Chengdu, 610041, P. R. China
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  • Shaobing Zhou

    Corresponding author
    1. School of Materials Science and Engineering, Key Laboratory of Advanced Technologies of Materials, Ministry of Education, Southwest Jiaotong University, Chengdu, 610031, P. R. China
    2. School of Life Science and Engineering, Southwest Jiaotong University, Chengdu 610031, Sichuan, P.R. China
    • School of Materials Science and Engineering, Key Laboratory of Advanced Technologies of Materials, Ministry of Education, Southwest Jiaotong University, Chengdu, 610031, P. R. China.
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Abstract

For cancer therapy, optimization of carrier features is necessary to effectively deliver the targeting agents to tumor sites. Biodegradable poly(ether-anhydrides) micelles with filamentous, rod-like, and spherical shapes are fabricated. Their size and morphology are characterized by AFM and TEM. The encapsulation of doxorubicin hydrochloride (DOX) into the micelles does not impact their shape. The effect of micellar shape on the drug loading capacity and encapsulation efficiency, as well as in vitro drug release, is investigated. The cellular uptakes are evaluated using fluorescence microscopy, confocal laser scanning microscopy and flow cytometry on co-cultures of human hepatoblastoma cell line (HepG2), lung epithelial cancer cell line (A549), and human nasopharyngeal epidermoid carcinoma cells (KB) and fibroblast normal cells mixed with the different shapes of DOX-loaded micelles. The results show that the spherical DOX-loaded micelles are more readily taken up by all types of cells. The impact of micellar shape on in vivo antitumor function is also assessed from changes of tumor volume, body weight loss, and survival rate of 4T1-bearing mice and the immunostaining of tumor sections for analysis of tumor cell proliferation. The results reveal that the filamentous DOX-loaded micelles possess the highest safety to body and the best therapeutic effects to artificial solid tumors. Therefore, the filamentous shape is deemed the most suitable morphology for design and engineering of drug vehicles for cancer therapy.

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