Injectable Functional Porous Carbon‐Loaded Hydrogel with Long‐Term Retention and Synergistic Anti‐Tumor Properties for Tumor Therapy

In situ therapies show significant promise for the treatment of unresectable tumors that lack tumor supply vessels. However, it remains a tremendous challenge to achieve precise delivery and sustained release of anti-tumor agents with synergistic anti-tumor efficacy. Here, a novel in situ injectable hydrogel (denoted as CFe/βCP+Cis hydrogel) has been designed by integrating β-CD-g-PEGMA (βCP) molecular brush hydrogel with functional carbon nanozyme (CFe) and cisplatin. The reversible gel network of βCP hydrogel and the rigid nanoscale architecture of CFe endow CFe/βCP+Cis hydrogel with properties conducive to injectability and long-term retention (more than 63 days). CFe and cisplatin mixed in hydrogel are both gradually released into the tumor tissue, facilitating the synergistic anti-tumor efficacy via ferroptosis and cytotoxicity. In addition, CFe/βCP hydrogel can reduce the M2-like/M1-like ratio of macrophages and promote the infiltration of CD8⁺ T cells in the tumor microenvironment to enhance anti-tumor immunity. As a result, the CFe/βCP+Cis hydrogel demonstrates significant potential for precise and sustained tumor treatment through chemodynamic therapy, chemotherapy, immunoregulation, and long-term retention properties.