1. Homotypic Targeted Photosensitive Nanointerferer for Tumor Cell Cycle Arrest to Boost Tumor Photoimmunotherapy
- Author
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Xue-Feng Bai, Ying Chen, Mei-Zhen Zou, Chu-Xin Li, Yu Zhang, Min-Jie Li, Si-Xue Cheng, and Xian-Zheng Zhang
- Subjects
Mice ,Cell Line, Tumor ,Colonic Neoplasms ,General Engineering ,Tumor Microenvironment ,General Physics and Astronomy ,Animals ,General Materials Science ,Immunotherapy ,Cell Cycle Checkpoints ,CD8-Positive T-Lymphocytes - Abstract
Recent advances in tumor immunotherapy mainly tend to remodel the immunosuppressive tumor microenvironment (TME) for immune enhancement. However, the complexity of TME makes it unlikely to achieve satisfactory therapeutic effects with any single intervention alone. Here, we focus on exposing intrinsic features of tumor cells to trigger direct pleiotropic antitumor immunity. We develop a photosensitive nanointerferer that is engineered with a nanoscale metal-organic framework decorated with tumor cell membranes for targeted delivery of a photosensitizer and small interfering RNA, which is used to knock down cyclin-dependent kinase 4 (Cdk4). Cdk4 blockade can arrest the cell cycle of tumor cells to facilitate antigen exposure and increase the expression level of programmed cell death protein ligand 1 (PD-L1). Under laser irradiation, photodynamic damage triggered by the nanointerferer induces the release of tumor antigens and recruitment of dendritic cells (DCs), thereby promoting the antitumor activity of CD8
- Published
- 2022