Radiotherapy is one of the most important means of cancer treatment, however, radiation can also cause adverse reactions and even serious injuries to the skin. Radiation‐induced excess reactive oxygen species (ROS) production and inflammatory infiltration make skin wounds difficult to heal compared to normal skin injuries. Herein, an antioxidant heparin‐mimetic peptide hydrogel (K16, KYKYEYEYAGEGDSS‐4Sa) is designed for radiation‐induced skin injury (RISI) repair. First, the K16 peptide can self‐assemble into a hydrogel with a 3D mesh‐like porous nanofiber structure, which can provide certain physical support for skin repair like extracellular matrix (ECM). Then, K16 hydrogel not only scavenges ROS and prevents radiation damage to cellular DNA, but also promotes cell proliferation, migration, and angiogenesis. Meanwhile, 4‐sulfobenzoic acid (4Sa) modified at the N‐terminal end of the K16 peptide can adsorb inflammatory cytokines, thus acting to eliminate inflammation at the wound site. In vivo experiments showed that K16 hydrogel can inhibit early wound degradation, reduce inflammatory infiltration, and promote angiogenesis and collagen deposition, thus promoting wound healing. Therefore, the K16 hydrogel designed in this study has good potential for application in the field of radiation‐induced skin injury repair.
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 αPD‐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.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.