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Trinity immune enhancing nanoparticles for boosting antitumor immune responses of immunogenic chemotherapy

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Abstract

Certain chemo drugs have been reported to potentially induce tumor-specific immune recognition by triggering immunogenic cell death (ICD), which provides a promising alternative way for cancer immunotherapy. However, the immunogenic effects of such treatments are still weak and robust systemic antitumor immune responses are rarely seen when these agents were used alone. Herein, we proposed a trinity immune enhancing nanoparticles (TIENs) for boosting antitumor immune responses of chemo agents. The TIENs was constructed with Food and Drug Administration (FDA) approved polylactic acid (PLA), canonical proton-sponging cationic polymer polyethyleneimine (PEI), and Toll-like receptor 9 (TLR9) agonist cytosine phosphate guanine oligodeoxynucleotide (CpG-ODN). In in vitro studies, the TIENs was proved to (1) promote antigen capturing, (2) antigen-presenting cells (APCs) activation, and (3) antigen cross-presentation. In in vivo studies, intratumorally injected TIENs greatly enhanced antitumor effect and robust immune responses of oxaliplatin and doxorubicin in murine CT26 and 4T1 tumor models, respectively. Furthermore, after decoration with a detachable shielding, the TIENs was proved to be effective in promoting the antitumor effects of chemo agents after intravenous injection. The combination of TIENs with clinically widely used chemo agents should be meaningful in boosting effective antitumor immune responses and cancer therapy.

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Acknowledgements

This work is financially supported by the National Natural Science Foundation of China (Nos. 51973215, 52025035, 52003268, 51829302, and 51833010), Bureau of International Cooperation Chinese Academy of Sciences (No. 121522KYSB20200029), the Jilin Province Science and Technology Development Plan (No. 2020122331JC), and the support from the Youth Innovation Promotion Association of Chinese Academy of Sciences (No. 2020232).

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Authors and Affiliations

  1. Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, 130022, China

    Yudi Xu, Sheng Ma, Jiayu Zhao, Xinghui Si, Zichao Huang, Yu Zhang, Wantong Song, Zhaohui Tang & Xuesi Chen

  2. University of Chinese Academy of Sciences, Beijing, 100039, China

    Yudi Xu

  3. University of Science and Technology of China, Hefei, 230026, China

    Jiayu Zhao, Xinghui Si, Zichao Huang, Zhaohui Tang & Xuesi Chen

  4. Jilin Biomedical Polymers Engineering Laboratory, Changchun, 130022, China

    Yudi Xu, Sheng Ma, Jiayu Zhao, Xinghui Si, Zichao Huang, Yu Zhang, Wantong Song, Zhaohui Tang & Xuesi Chen

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  1. Yudi Xu
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  2. Sheng Ma
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  3. Jiayu Zhao
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  4. Xinghui Si
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  7. Wantong Song
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  8. Zhaohui Tang
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Correspondence to Wantong Song or Zhaohui Tang.

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Xu, Y., Ma, S., Zhao, J. et al. Trinity immune enhancing nanoparticles for boosting antitumor immune responses of immunogenic chemotherapy. Nano Res. 15, 1183–1192 (2022). https://doi.org/10.1007/s12274-021-3622-6

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