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

作　　者：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 

机构地区：[1]No.1 Department of Neurology,China-Japan Union Hospital of Jilin University,Changchun,130033,China [2]Key Laboratory of Polymer Ecomaterials,Changchun Institute of Applied Chemistry,Chinese Academy of Sciences,Changchun,130022,China [3]Jilin Biomedical Polymers Engineering Laboratory,Changchun,130022,China [4]School of Applied Chemistry and Engineering,University of Science and Technology of China,Hefei,230026,China [5]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

出　　处：《Chinese Journal of Polymer Science》2023年第7期1059-1068,共10页高分子科学（英文版）

基　　金：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);the Jilin Provincial International Cooperation Key Laboratory of Biomedical Polymers(No.20210504001GH).

摘　　要：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(L-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.

关 键 词：POLYPEPTIDE Phenylboronic acid Boron-nitrogen coordination Interleukin 2 ROS-responsive 

分 类 号：TQ460.1[化学工程—制药化工] R730.51[医药卫生—肿瘤]