IL-2-loaded Polypeptide Nanoparticles for Enhanced Anti-cancer Immunotherapy

Xiao-Shuang Wang; Zhao-Shi Zheng; Meng-Fei Zheng; Di Wang; Hong-Lei Zhang; Zhen-Qian Zhang; Zhi-Lin Liu; Zhao-Hui Tang; Xue-Mei Han

doi:10.1007/s10118-023-2898-2

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IL-2-loaded Polypeptide Nanoparticles for Enhanced Anti-cancer Immunotherapy

RESEARCH ARTICLE | Updated：2023-06-14

- IL-2-loaded Polypeptide Nanoparticles for Enhanced Anti-cancer Immunotherapy
- IL-2-loaded Polypeptide Nanoparticles for Enhanced Anti-cancer Immunotherapy
- 高分子科学（英文版） 2023年41卷第7期页码：1059-1068
- Affiliations：
  
  a.No.1 Department of Neurology, China-Japan Union Hospital of Jilin University, Changchun 130033, China
  b.Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, China
  c.Jilin Biomedical Polymers Engineering Laboratory, Changchun 130022, China
  d.School of Applied Chemistry and Engineering, University of Science and Technology of China, Hefei 230026, China
  e.Key Laboratory of Environmentally Friendly Chemistry and Applications of Ministry of Education and Key Laboratory of Polymeric Materials & Application Technology of Hunan Province, Xiangtan University, Xiangtan 411105, China
- Author bio：
  
  ztang@ciac.ac.cn (Z.H.T.)
  hxm@jlu.edu.cn (X.M.H.)
- Funds：
  
  This work was financially supported by the National Natural Science Foundation of China (Nos. 52025035, 51873206 and 52203198), the Project of Health research talents Project of Jilin Province (No. 2020SCZ06), the Project of Jilin Province Development and Reform Commission (No. 2021C043-6), and the Jilin Provincial International Cooperation Key Laboratory of Biomedical Polymers (No. 20210504001GH).;Electronic supplementary information (ESI) is available free of charge in the online version of this article at http://doi.org/10.1007/s10118-023-2898-2.
- DOI：10.1007/s10118-023-2898-2
  中图分类号：
- 收稿：2022-09-08，
  
  修回：2022-10-26，
  
  录用：2022-11-4，
  
  网络首发：2023-01-16，
  
  纸质出版：2023-07-01
- Accepted：
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Wang, X. S.; Zheng, Z. S.; Zheng, M. F.; Wang, D.; Zhang, H. L.; Zhang, Z. Q.; Liu, Z. L.; Tang, Z. H.; Han, X. M. IL-2-loaded polypeptide nanoparticles for enhanced anti-cancer immunotherapy. Chinese J. Polym. Sci. 2023, 41, 1059–1068

Xiao-Shuang Wang, Zhao-Shi Zheng, Meng-Fei Zheng, et al. IL-2-loaded Polypeptide Nanoparticles for Enhanced Anti-cancer Immunotherapy[J]. Chinese Journal of Polymer Science, 2023, 41(7): 1059-1068.
Wang, X. S.; Zheng, Z. S.; Zheng, M. F.; Wang, D.; Zhang, H. L.; Zhang, Z. Q.; Liu, Z. L.; Tang, Z. H.; Han, X. M. IL-2-loaded polypeptide nanoparticles for enhanced anti-cancer immunotherapy. Chinese J. Polym. Sci. 2023, 41, 1059–1068 DOI： 10.1007/s10118-023-2898-2.

Xiao-Shuang Wang, Zhao-Shi Zheng, Meng-Fei Zheng, et al. IL-2-loaded Polypeptide Nanoparticles for Enhanced Anti-cancer Immunotherapy[J]. Chinese Journal of Polymer Science, 2023, 41(7): 1059-1068. DOI： 10.1007/s10118-023-2898-2.

摘要

This work described a novel IL-2-loaded polypeptide nanomedicine (P-IL-2) with a 3.15-fold longer circulation time than IL-2 and a ROS-responsive drug release capability. P-IL-2 promotes the proliferation of CD8+ T cells continuously and activates anti-tumor immune response

resulting in better anti-tumor effect in combination with anti-CTLA-4.

Abstract

Interleukin 2 (IL-2) is widely used as an active immunotherapeutic agent in clinical metastatic cancers. However

its therapeutic concentrations do not last long due to its short half-life. Thus

only a transient proliferation of the anti-cancer CD8

T cells can be achieved

resulting in poor efficacy. Therefore

the aim of this work was to create a system that promotes CD8

T cell proliferation at the tumor site using IL-2 persistently present and activates an anti-cancer immune response. This goal was achieved by the design of the IL-2-loaded polypeptide nanoparticles (P-IL-2) where methoxy poly(ethylene glycol) block poly-[(

N-2

-hydroxyethyl)-aspartamide] phenylboronic acid was used to encapsulate IL-2 through boron-nitrogen coordination with poly(

-lysine). P-IL-2 significantly prolonged the circulation time of IL-2 and achieved a selective drug release at the tumor site in the presence of high levels of reactive oxygen species

thus activating an anti-cancer immune response and exerting a better anti-cancer effect. The half-life of P-IL-2 was 3.15-fold higher than that of IL-2

and the quantity of CD8

T cells after using P-IL-2 was 1.89-fold higher than that after using IL-2. In addition

the combination of P-IL-2 and anti-CTLA-4 monoclonal antibody resulted in an enhanced immune activation. Hence

this work provides a new approach to improve the efficacy of IL-2 in anti-cancer immunotherapy.

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references

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