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Simultaneous delivery of anti-miRNA and docetaxel with supramolecular self-assembled “chitosome” for improving chemosensitivity of triple negative breast cancer cells

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Abstract

At present, treating of triple negative breast cancer (TNBC) mainly depends on chemotherapy with more toxic side effects, but the effect is limited and it is highly prone to drug resistance. Gene therapy using anti-microRNAs maybe one of alternative therapeutic strategies. Due to the poor cell permeability and significant in vivo decomposition rate of anti-microRNAs, which limits their clinical application, we developed a core-shell supramolecular nanovector of “chitosome” that were self-assembled from the synthetic amphiphilic chitosan derivatives. The constructed chitosomes could co-load hydrophilic anti-miR-21 and hydrophobic docetaxel (DTX) into one combo nanocarrier with entrapment efficiency of more than 80%, as well as spherical morphology and average particle size of 90 nm. In comparison with the naked ones, anti-miR-21 encapsulated with chitosomes showed significantly increased cellular transfection and stability against degradation by nuclease in serum. Compared with DTX or anti-miR-21 formulations used alone, the co-delivery of the two drugs with the combo chitosome obtained improved chemosensitivity of TNBC cells to DTX treatment through their synergistic mechanisms. Taken together, the developed chitosome could be a promising candidate for simultaneous delivery of insoluble chemotherapeutic drugs and gene agents for TNBC therapy.

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Funding

This research was funded by the Basic and Frontier Technology Research Projects from Science and Technology Department of Henan Province (No. 142300410271, the screening and analysis of specific microRNA expression in peripheral blood of patients with bone metastasis after breast cancer surgery).

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Author notes

  1. Xianfu Sun and Haipeng Xu contributed equally to this work.

Authors and Affiliations

  1. Department of Breast Oncology, The Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, 450008, Henan, China

    Xianfu Sun, Tao Huang & Junzhao Wu

  2. Department of Thoracic Oncology, Fujian Cancer Hospital, Fujian Medical University Cancer Hospital, Fuzhou, 350014, Fujian, China

    Haipeng Xu

  3. Department of Pathology, The Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, 450008, Henan, China

    Chengjuan Zhang

  4. Department of Medical Oncology, The Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, 450008, Henan, China

    Suxia Luo

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  1. Xianfu Sun
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Correspondence to Suxia Luo.

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Sun, X., Xu, H., Huang, T. et al. Simultaneous delivery of anti-miRNA and docetaxel with supramolecular self-assembled “chitosome” for improving chemosensitivity of triple negative breast cancer cells. Drug Deliv. and Transl. Res. 11, 192–204 (2021). https://doi.org/10.1007/s13346-020-00779-4

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