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A Redox-responsive Prodrug Nanogel of TLR7/8 Agonist for Improved Cancer Immunotherapy

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Abstract

The existence of tumor immunosuppressive microenvironment (TIME) is the major determinant for the poor efficacy of current tumor immunotherapy. Tumor-associated macrophages (TAMs) tend to become tumor-promoting M2-like phenotype and hinder immune response in solid tumors. Repolarization of TAMs from M2 to anti-tumor M1 phenotype is robust for remodeling the TIME. Herein, we developed a redox-responsive nanogel as the delivery system of Toll-like receptor 7 and 8 (TLR7/8) agonist (R848) prodrug for potent cancer immunotherapy. The nanogel (denoted as R848-Gel) was obtained by emulsion polymerization of HSEMA and R848 prodrug (R848-HSEMA), whose size was appropriate 100 nm. R848-Gel could be internalized by macrophages and dendritic cells in vitro, and effectively repolarized M2 into M1 macrophages and promoted the maturation of antigen-presenting cells. In vivo study indicated that the R848-Gel showed a stronger tumor inhibitory effect and no drastic body weight change compared with free drug. Immune cell analysis after the treatment indicated that R848-Gel was helpful to activating the TIME. In summary, this study provides a simple but effective vehicle for R848 to improve cancer immunotherapy.

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Acknowledgments

This work was financially supported by the National Natural Science Foundation of China (Nos. 51922043, 52173122 and 31771091), Guangdong Provincial Program (No. 2017GC010304), Science and Technology Planning Project of Ganzhou (No. 202101074816), and Fundamental Research Funds for Central Universities.

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  1. These authors contributed equally to this work.

Authors and Affiliations

  1. School of Medicine, South China University of Technology, Guangzhou, 510006, China

    Kai-Shuo Wang, Zhen-Lin Gao, Sui-Juan Zheng & Jin-Zhi Du

  2. School of Biomedical Sciences and Engineering, Guangzhou International Campus, South China University of Technology, Guangzhou, 511442, China

    Yu-Feng Jin, Qi-Song Tong, Yong-Cong Huang, Jing-Yang Zhang & Jun Wang

  3. National Engineering Research Center for Tissue Restoration and Reconstruction, South China University of Technology, Guangzhou, 510006, China

    Jun Wang

  4. Key Laboratory of Biomedical Materials and Engineering of the Ministry of Education, and Guangdong Provincial Key Laboratory of Biomedical Engineering, South China University of Technology, Guangzhou, 510006, China

    Jin-Zhi Du

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  1. Kai-Shuo Wang
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Correspondence to Jun Wang or Jin-Zhi Du.

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Wang, KS., Jin, YF., Tong, QS. et al. A Redox-responsive Prodrug Nanogel of TLR7/8 Agonist for Improved Cancer Immunotherapy. Chin J Polym Sci 41, 32–39 (2023). https://doi.org/10.1007/s10118-022-2831-0

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  • DOI: https://doi.org/10.1007/s10118-022-2831-0

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