期刊
MACROMOLECULAR BIOSCIENCE
卷 22, 期 12, 页码 -出版社
WILEY-V C H VERLAG GMBH
DOI: 10.1002/mabi.202200359
关键词
immune checkpoint blockade; photodynamic therapy; reactive nitrogen species; tumor microenvironment; tumor-associated macrophages
资金
- National Natural Science Foundation of China [81971731, 81971733, 82172082]
- Science Foundation for Distinguished Young Scholars of Tianjin [19JCJQJC62200]
- CAMS Innovation Fund for Medical Sciences (CIFMS) [2021-I2M-1-042, 2021-I2M-1-058]
- Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences [2018PT35031]
A coassembled hydrogel that can cascade release ROS/NO/RNS and strengthen antitumor T cell responses has been developed, which significantly improves the efficacy of immune checkpoint blockade therapy in photodynamic therapy. Reprogramming of tumor-associated macrophages (TAMs) further alleviates the immunosuppressive situation in the tumor microenvironment.
Photodynamic therapy (PDT) has attracted much attention in cancer treatment due to its tumor selectivity and noninvasive nature. Recent studies have demonstrated that PDT mediated reactive oxygen species (ROS) generation in tumor microenvironment (TME) synergistically improves the efficacy of immune checkpoint blockade (ICB) therapy. However, the instability and short half-life of the ROS generated by PDT limit its clinical applications. Herein, a coassembled peptide hydrogel comprising two short peptides that contained the same assembly unit, Ce6-KKFKFEFEF (KEF-Ce6) and RRRRRRRR-KFKFEFEF (KEF-R8) is developed. When exposed to 635 nm laser irradiation, KEF-Ce6 released ROS, while KEF-R8 plays as nitric oxide (NO) donor. Subsequently, ROS reacts with NO to produce reactive nitrogen species (RNS). Both in vitro and in vivo experiments prove that converting ROS into more cytotoxic RNS caused intense cell death. Importantly, it is observed that tumor-associated macrophages (TAMs) are polarized to proinflammatory types (M1-type) by the RNS-based PDT. The increase of M1 macrophages relieves the immunosuppressive situation in TME. Thus, when combined with alpha PD-L1 treatment, the survival time of tumor-bearing mice is prolonged. Overall, a simple yet efficient coassembled hydrogel that can cascade release ROS/NO/RNS and strengthen antitumor T cell responses to boost cancer immunotherapy by reprogramming TAMs is provided.
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