Glutamine Metabolism-Regulated Nanoparticles to Enhance Chemoimmunotherapy by Increasing Antigen Presentation Efficiency

• Published in: ACS applied materials & interfaces Vol. 14; no. 7; pp. 8753 - 8765
• Main Authors: Du, Bin, Jiao, Qingqing, Bai, Yimeng, Yu, Min, Pang, Mengxue, Zhao, Mengmeng, Ma, Huizhen, Yao, Hanchun
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 23.02.2022
• Subjects: Antigen Presentation; Biological and Medical Applications of Materials and Interfaces; Dendritic Cells; Glutamine; Immunotherapy - methods; Nanoparticles; Tumor Microenvironment; glutamine metabolism; chemoimmunotherapy; antigen presentation; immunogenic cell death; immune activation
• ISSN: 1944-8244; 1944-8252
• DOI: 10.1021/acsami.1c21417

Although the strategies to induce dendritic cells (DCs) maturation and promote their antigen presentation can stimulate the tumor immune response, the endogenous deficiency and immunosuppression of DCs reduce antigen utilization, which limits antigen presentation efficiency and reduces immunotherapy effectiveness. Here, we report an endogenous stimulus-responsive nanodelivery system (DOX@HFn-MSO@PGZL). On the one hand, doxorubicin (DOX) promoted antigen presentation by DCs after the immunogenic death of tumor cells. On the other hand, l-methionine sulfoximine (MSO) regulated the glutamine metabolism of tumor-associated macrophages (TAMs) to induce a shift toward the M1-type. M1-TAMs synergistically presented antigens with mature DCs and were more frequently produced to destroy the tumor suppressive immune microenvironment, resulting in the alleviation of DCs functional inhibition. Ultimately, the antigen presentation efficiency was improved, completely activating tumor immunity and exhibiting powerful antitumor effects.