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Research Article

Unified D-α-Tocopherol 5-Fu/SAHA bioconjugates self-assemble as complex nanodrug for optimized combination therapy

    Leiqiang Han

    Department of Pharmaceutics, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, 44 Wenhua Xi Road, Jinan 250012, Shandong, China

    ,
    Tianqi Wang

    Department of Pharmaceutics, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, 44 Wenhua Xi Road, Jinan 250012, Shandong, China

    ,
    Shengjun Mu

    Department of Pharmaceutics, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, 44 Wenhua Xi Road, Jinan 250012, Shandong, China

    ,
    Xiaolan Yin

    Department of Pharmaceutics, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, 44 Wenhua Xi Road, Jinan 250012, Shandong, China

    ,
    Shuang Liang

    Department of Pharmaceutics, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, 44 Wenhua Xi Road, Jinan 250012, Shandong, China

    ,
    Hao Fang

    Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, 44 Wenhua Xi Road, Jinan 250012, Shandong, China

    ,
    Yongjun Liu

    **Co-author for correspondence:

    E-mail Address: liuyongjun@sdu.edu.cn

    Department of Pharmaceutics, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, 44 Wenhua Xi Road, Jinan 250012, Shandong, China

    &
    Na Zhang

    *Author for correspondence:

    E-mail Address: zhangnancy9@sdu.edu.cn

    Department of Pharmaceutics, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, 44 Wenhua Xi Road, Jinan 250012, Shandong, China

    Published Online:https://doi.org/10.2217/nnm-2017-0316

    Aim: To optimize the synergistic efficacy of combination therapy with controlled molar ratio, complex small molecule-based nanodrug (Co-SMND) of 5-fluorouracil (5-Fu)/vorinostat (SAHA) was developed. Materials & methods: Co-SMND with various ratios of 5-Fu-D-α-tocopherol (VE)/SAHA-VE were prepared and characterized including co-assembly mechanism, hydrolytic stability, cytotoxicity, synergistic effect and apoptosis inducing ability. The antitumor activity, systematic toxicity and biodistribution of optimized Co-SMND were evaluated in CT-26 bearing BALB/c mouse. Results: Maximal synergistic effect of Co-SMND could be obtained via simply adjusting the feeding molar ratio. The optimized Co-SMND showed superior in vivo antitumor efficacy, upregulated security and selective intratumoral accumulation. Conclusion: Such Co-SMND is of great significance for future clinical translation, and would be an efficient platform for combination chemotherapy.

    Papers of special note have been highlighted as: • of interest; •• of considerable interest

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