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

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 effic...

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Published in:Chinese journal of polymer science 2023-07, Vol.41 (7), p.1059-1068
Main Authors: Wang, Xiao-Shuang, Zheng, Zhao-Shi, Zheng, Meng-Fei, Wang, Di, Zhang, Hong-Lei, Zhang, Zhen-Qian, Liu, Zhi-Lin, Tang, Zhao-Hui, Han, Xue-Mei
Format: Article
Language:English
Subjects:
Anticancer properties
Cancer
Characterization and Evaluation of Materials
Chemistry
Chemistry and Materials Science
Condensed Matter Physics
Effectiveness
Half-life
Immune system
Immunotherapy
Industrial Chemistry/Chemical Engineering
Interleukins
Lymphocytes
Lysine
Monoclonal antibodies
Nanoparticles
Polyethylene glycol
Polymer Sciences
Polypeptides
Research Article
Tumors
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Summary: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.
ISSN:0256-7679
1439-6203
DOI:10.1007/s10118-023-2898-2