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Local T regulatory cells depletion by an integrated nanodrug system for efficient chem-immunotherapy of tumor

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Abstract

T regulatory (Treg) cell is a major immunosuppressive factor that restrains the antitumor effect of immunotherapy, because it gets more after the immune activation and is hardly to be eliminated. Here, an acid-sensitive integrated nanodrug system is designed to activate antitumor immune response as well as locally deplete Treg cells with low side effect. The nanosystem is synthetized by coordinating doxorubicin (DOX) and pentoxifylline (PTX) with Zn ions, then stabilized via liposome encapsulation (denoted as DTX@Lipo). DTX@Lipo can activate antitumor immune effect by chemotherapy of DOX. Besides, the release of PTX inhibits c-Rel expression, leading to the reduction of Treg cells in tumor site. Owing to the good tumor accumulation and local drug release ability, DTX@Lipo exhibits better biosafety and convenience than traditional antibody blockade method for Treg cells depletion. According to the results of in vivo experiments, the nanodrug system can significantly increase the ratio between effector T (Teff) cells and Treg cells locally, resulting in an immunoactivated tumor microenvironment. Importantly, it exhibits significant antitumor effect when combined with PD-1 blockade therapy, providing great potential for tumor therapy.

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Acknowledgements

This work was supported by the National Natural Science Foundation of China (51833007, 51703168, 51690152, 21674084).

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  1. These authors contributed equally to this work.

Authors and Affiliations

  1. Key Laboratory of Biomedical Polymers of Ministry of Education, Department of Chemistry, Wuhan University, Wuhan, 430072, China

    Fan Gao, Qian Cheng, Miao-Deng Liu, Lei Rong, Chuan-Jun Liu & Xian-Zheng Zhang

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  1. Fan Gao
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  2. Qian Cheng
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  3. Miao-Deng Liu
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  4. Lei Rong
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  5. Chuan-Jun Liu
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  6. Xian-Zheng Zhang
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Correspondence to Xian-Zheng Zhang.

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Conflict of interest The authors declare that they have no conflict of interest.

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Gao, F., Cheng, Q., Liu, MD. et al. Local T regulatory cells depletion by an integrated nanodrug system for efficient chem-immunotherapy of tumor. Sci. China Chem. 62, 1230–1244 (2019). https://doi.org/10.1007/s11426-019-9507-x

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  • DOI: https://doi.org/10.1007/s11426-019-9507-x

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