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Immunostimulatory nanomedicines synergize with checkpoint blockade immunotherapy to eradicate colorectal tumors

Author

Listed:
  • Xiaopin Duan

    (The University of Chicago
    Southern Medical University)

  • Christina Chan

    (The University of Chicago)

  • Wenbo Han

    (The University of Chicago)

  • Nining Guo

    (The University of Chicago
    The University of Chicago)

  • Ralph R. Weichselbaum

    (The University of Chicago)

  • Wenbin Lin

    (The University of Chicago
    The University of Chicago)

Abstract

Nanoparticles can potentially stimulate tumour microenvironments to elicit antitumour immunity. Herein, we demonstrate effective immunotherapy of colorectal cancer via systemic delivery of an immunostimulatory chemotherapeutic combination in nanoscale coordination polymer (NCP) core-shell particles. Oxaliplatin and dihydroartemesinin have contrasting physicochemical properties but strong synergy in reactive oxygen species (ROS) generation and anticancer activity. The combined ROS generation is harnessed for immune activation to synergize with an anti-PD-L1 antibody for the treatment of murine colorectal cancer tumours. The favourable biodistribution and tumour uptake of NCPs and the absence of peripheral neuropathy allow for repeated dosing to afford 100% tumour eradication. The involvement of innate and adaptive immune systems elicit strong and long lasting antitumour immunity which prevents tumour formation when cured mice are challenged with cancer cells. The intrinsically biodegradable, well tolerated, and systemically available immunostimulatory NCP promises to enter clinical testing as an immunotherapy against colorectal cancer.

Suggested Citation

  • Xiaopin Duan & Christina Chan & Wenbo Han & Nining Guo & Ralph R. Weichselbaum & Wenbin Lin, 2019. "Immunostimulatory nanomedicines synergize with checkpoint blockade immunotherapy to eradicate colorectal tumors," Nature Communications, Nature, vol. 10(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-09221-x
    DOI: 10.1038/s41467-019-09221-x
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    Cited by:

    1. Chaoyu Wang & Ruoshi Zhang & Jia He & Lvshan Yu & Xinyan Li & Junxia Zhang & Sai Li & Conggang Zhang & Jonathan C. Kagan & Jeffrey M. Karp & Rui Kuai, 2023. "Ultrasound-responsive low-dose doxorubicin liposomes trigger mitochondrial DNA release and activate cGAS-STING-mediated antitumour immunity," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    2. Yuxin Guo & Shao-Zhe Wang & Xinping Zhang & Hao-Ran Jia & Ya-Xuan Zhu & Xiaodong Zhang & Ge Gao & Yao-Wen Jiang & Chengcheng Li & Xiaokai Chen & Shun-Yu Wu & Yi Liu & Fu-Gen Wu, 2022. "In situ generation of micrometer-sized tumor cell-derived vesicles as autologous cancer vaccines for boosting systemic immune responses," Nature Communications, Nature, vol. 13(1), pages 1-20, December.

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