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A (Traditional Chinese Medicine) TCM-Inspired Doxorubicin Resistance Reversing Strategy: Preparation, Characterization, and Application of a Co-loaded pH-Sensitive Liposome

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Abstract

In this study, nano-strategy for combined medication of active compounds from traditional Chinese medicine herbs was proposed to achieve the synergistic effects of inhibiting the doxorubicin (DOX) resistance, reducing the cardio-toxicity, and improving the treatment efficacy simultaneously. Dihydroartemisinin (DHA) and tetrandrine (TET) were co-delivered for the first time to treat DOX resistance of breast cancer with multi-pathway mechanism. Tumor micro-environment sensitivity prescription was adopted to enhance the reversal effect of DOX resistance nearly 50 times (resistance index, RI was 46.70) and uptake ability. The DHA-TET pH-sensitive liposomes (DHA-TET pH-sensitive LPs) had a good spherical structure and a uniform dispersion structure with particle size, polydispersity index (PDI), and zeta potential of 112.20 ± 4.80 nm, 0.20 ± 0.02, and − 8.63 ± 0.74 Mv, and was stable until 14 days under the storage environment of 4°C and for 6 months at room temperature environment. With the DOX resistance reversing ability increased, the inhibition effect of DHA-TET pH-sensitive LPs on both MCF-7/ADR cells and MCF-7 cells was significantly enhanced; meanwhile, the toxicity on cardiac cell (H9c2) was lowered. Ferroptosis induced by the DHA was investigated showing that the intracellular reactive oxygen species (ROS) and lipid peroxidation were increased to promote the synergistic effect through the due-loaded nano-carrier, providing a promising alternative for future clinical application.

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Funding

This work was supported by the National Natural Science Foundation of China (grant No. 82274236) and the Tianjin Research Innovation Project for Postgraduate Students (CN) (grant No. 2021YJSB284).

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Author notes

  1. Xueyan Zhang and Hua Liu contributed equally to this work.

Authors and Affiliations

  1. State Key Laboratory of Component-Based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, 301617, China

    Xueyan Zhang, Hua Liu, Na Li, Jiayang Li & Meng Wang

  2. School of Chinese Materia Medica, Tianjin University of Traditional Chinese Medicine, Tianjin, 301617, China

    Xueyan Zhang, Na Li & Xiaoliang Ren

  3. Haihe Laboratory of Modern Chinese Medicine, Tianjin, 301617, People’s Republic of China

    Meng Wang

Authors
  1. Xueyan Zhang
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Contributions

All authors contributed to the study conception and design. Xueyan Zhang: software and writing-review and editing; Hua Liu: writing-original draft and data curation; Na Li: investigation and methodology; Jiayang Li: formal analysis and software; Meng Wang and Xiaoliang Ren: conceptualization, project administration, and supervision. All authors read and approved the final manuscript.

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Correspondence to Meng Wang or Xiaoliang Ren.

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Zhang, X., Liu, H., Li, N. et al. A (Traditional Chinese Medicine) TCM-Inspired Doxorubicin Resistance Reversing Strategy: Preparation, Characterization, and Application of a Co-loaded pH-Sensitive Liposome. AAPS PharmSciTech 24, 181 (2023). https://doi.org/10.1208/s12249-023-02630-8

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