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Nanoliposomal multi-drug delivery system with reduced toxicity and multi-drug resistance

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Abstract

Chemotherapy is a key medical method for cancer treatment because a large amount of patients are not suitable for surgeries, and the multi-drug resistance (MDR) and drug toxicity are still the major obstacles for clinical advancement. Here, we report the development of a nanoliposomal multi-drug delivery system with lapatinib and doxorubicin co-loaded in PEGylated nanoliposomes (Lip-LPT-DOX). Lip-LPT-DOX showed great chemosensitization of two human lung adenocarcinoma cell lines. LPT loaded in nanoliposomes could inhibit the function of ABC transporters, which could pump drugs out of cancer cells and lead to decreased intracellular drug accumulation. Lip-LPT-DOX showed a uniform size distribution and high loading efficiency with negligible drug leakage. Compared to clinical formulation, liposomal DOX (Lip-DOX), both intracellular DOX accumulation and therapeutic efficiency of Lip-LPT-DOX were significantly improved. Lip-LPT-DOX with half amount of DOX as Lip-DOX showed higher therapeutic efficiency, and it exhibited negligible toxicity to somatic cells, indicating the significantly reduced side effects. This novel nanoliposomal multi-drug delivery system provided a promising chemosensitization strategy that could likely overcome MDR and reduce the administration dose of DOX in cancer chemotherapy.

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Acknowledgements

This research was supported by the National Natural Science Funds for Innovation Research Groups (21621004), National Natural Science Funds for Excellent Young Scholars (21422605), the Qingdao National Laboratory for Marine Science and Technology (QNLM2016ORP0407), Tianjin Natural Science Foundation (18JCYBJC29500).

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Author notes

  1. Jing Yang and Chiyu Wen have contributed equally to this work.

Authors and Affiliations

  1. Department of Biochemical Engineering, School of Chemical Engineering and Technology, Tianjin University, Tianjin, 300350, China

    Jing Yang, Chiyu Wen, Chao Pan, Hongshuang Guo, Weiqiang Zhao, Jiamin Zhang, Yingnan Zhu, Yumiao Zhang & Lei Zhang

  2. Frontier Science Center for Synthetic Biology and Key Laboratory of Systems Bioengineering (MOE), School of Chemical Engineering and Technology, Tianjin University, Tianjin, 300350, China

    Jing Yang, Chiyu Wen, Chao Pan, Hongshuang Guo, Weiqiang Zhao, Jiamin Zhang, Yingnan Zhu, Yumiao Zhang & Lei Zhang

  3. Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), Tianjin University, Tianjin, 300350, China

    Jing Yang, Chiyu Wen, Chao Pan, Hongshuang Guo, Weiqiang Zhao, Jiamin Zhang, Yingnan Zhu, Yumiao Zhang & Lei Zhang

  4. Qingdao Institute for Marine Technology, Tianjin University, Qingdao, 266235, China

    Jing Yang, Chiyu Wen, Chao Pan, Hongshuang Guo, Weiqiang Zhao, Jiamin Zhang, Yingnan Zhu & Lei Zhang

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  1. Jing Yang
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Yang, J., Wen, C., Pan, C. et al. Nanoliposomal multi-drug delivery system with reduced toxicity and multi-drug resistance. J Mater Sci 54, 9718–9728 (2019). https://doi.org/10.1007/s10853-019-03573-x

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