期刊
ACS APPLIED MATERIALS & INTERFACES
卷 13, 期 47, 页码 55890-55901出版社
AMER CHEMICAL SOC
DOI: 10.1021/acsami.1c17498
关键词
artificial antigen-presenting cells; nanocatalysts; tumor microenvironment; tumor metastasis; immunotherapy
资金
- National Natural Science Foundation of China [81902198, 81871482]
- Guangdong Basic and Applied Basic Research Foundation [2020A1515010398, 2019A1515110328]
- China National Postdoctoral Program for Innovative Talents [BX20190150]
- China Postdoctoral Science Foundation [2019M662980]
- President Foundation of Zhujiang Hospital, Southern Medical University [yzjj2018rc09]
- Institute of Biomedical Engineering, Science and Technology of the University of Oklahoma
In this study, biomimetic artificial antigen-presenting cells (aAPCs) were developed using ultrathin MnOx nanoparticles functionalized with T-cell activators and tumor cell membranes to enhance lung metastasis immunotherapy. These aAPCs efficiently expanded and activated intratumoral CD8(+) T cells and dendritic cells, while regulating the tumor microenvironment (TME) to facilitate T-cell survival.
Effective expansion of T-cells without ex vivo stimulation and maintenance of their antitumor functions in the complex tumor microenvironment (TME) are still daunting challenges in T-cell-based immunotherapy. Here, we developed biomimetic artificial antigenpresenting cells (aAPCs), ultrathin MnOx nanoparticles (NPs) functionalized with T-cell activators (anti-CD3/CD28 mAbs, CD), and tumor cell membranes (CMs) for enhanced lung metastasis immunotherapy. The aAPCs, termed CD-MnOx@CM, not only efficiently enhanced the expansion and activation of intratumoral CD8(+) cytotoxic T-cells and dendritic cells after homing to homotypic metastatic tumors but also regulated the TME to facilitate T-cell survival through catalyzing the decomposition of intratumoral H2O2 into O-2. Consequently, the aAPCs significantly inhibited the development of lung metastatic nodules and extended the survival of a B16-F10 melanoma metastasis model, while minimizing adverse events. Our work represents a new biomaterial strategy of inhibiting tumor metastasis through targeted TME regulation and in situ T-cell-based immunotherapy.
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