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

Kai-Shuo Wang; Yu-Feng Jin; Qi-Song Tong; Yong-Cong Huang; Zhen-Lin Gao; Sui-Juan Zheng; Jing-Yang Zhang; Jun Wang; Jin-Zhi Du

doi:10.1007/s10118-022-2831-0

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

RESEARCH ARTICLE | Updated：2022-12-19

- A Redox-responsive Prodrug Nanogel of TLR7/8 Agonist for Improved Cancer Immunotherapy
- Chinese Journal of Polymer Science Vol. 41, Issue 1, Pages: 32-39(2023)
- Affiliations：
  
  a.School of Medicine, South China University of Technology, Guangzhou 510006, China
  b.School of Biomedical Sciences and Engineering, Guangzhou International Campus, South China University of Technology, Guangzhou 511442, China
  c.National Engineering Research Center for Tissue Restoration and Reconstruction, South China University of Technology, Guangzhou 510006, China
  d.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
- Author bio：
  
  mcjwang@scut.edu.cn (J.W.)
  djzhi@scut.edu.cn (J.Z.D.)
- Funds：
- DOI：10.1007/s10118-022-2831-0
  CLC：
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Kai-Shuo Wang, Yu-Feng Jin, Qi-Song Tong, et al. A Redox-responsive Prodrug Nanogel of TLR7/8 Agonist for Improved Cancer Immunotherapy. [J]. Chinese Journal of Polymer Science 41(1):32-39(2023)
DOI：

Kai-Shuo Wang, Yu-Feng Jin, Qi-Song Tong, et al. A Redox-responsive Prodrug Nanogel of TLR7/8 Agonist for Improved Cancer Immunotherapy. [J]. Chinese Journal of Polymer Science 41(1):32-39(2023) DOI： 10.1007/s10118-022-2831-0.

摘要

A redox-responsive R848-Gel was obtained by emulsion polymerization of HSEMA and R848 prodrug (R848-HSEMA). The R848-Gel reprograms M2-type macrophages to M1-type and stimulates dendritic cells (DCs) activation, reverses the immunosuppression of the tumor microenvironment and finally induces robust anti-tumor immune response.

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.

关键词

Keywords

NanogelDrug deliveryTumor-associated macrophageMacrophage repolarizationCancer immunotherapy

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