LAUSR

Photodynamic therapy (PDT) has attracted much attention in cancer treatment due to its tumor selectivity and non-invasive 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, we developed a co-assembled peptide hydrogel comprising two short peptides that contained the same assembly unit, Ce6-KKFKFEFEF (KEF-Ce6) and RRRRRRRR-KFKFEFEF (KEF-R8). When exposed to 635 nm laser irradiation, KEF-Ce6 released ROS, while KEF-R8 played as nitric oxide (NO) donor. Subsequently, ROS reacted with NO to produce reactive nitrogen species (RNS). Both in vitro and in vivo experiments proved that converting ROS into more cytotoxic RNS caused intense cell death. Importantly, we observed that tumor-associated macrophages (TAMs) were polarized to proinflammatory types (M1-type) by the RNS-based PDT. The increase of M1 macrophages relieved the immunosuppressive situation in TME. Thus, when combined with αPD-L1 treatment, the survival time of tumor-bearing mice was prolonged. Overall, we provided a simple yet efficient co-assembled hydrogel that could cascade release ROS/NO/RNS and strengthen anti-tumor T cell responses to boost cancer immunotherapy by reprogramming TAMs. This article is protected by copyright. All rights reserved.