Dual-functional cationic hydrogel engineered for simultaneous prevention of postoperative tumor recurrence and wound infection

Postoperative recurrence and Infection continue to pose major challenges after tumor resection. To address these, we developed a multifunctional nanocomposite hydrogel, designated as Gel@CAR-M@Mn@ELE. It is constructed by encapsulating CAR-M@Mn@ELE and immunomodulatory/Antibacterial Dendrobium officinale polysaccharide (DOP) within a quaternary ammonium-modified gelatin methacryloyl hydrogel matrix. The CAR-M@Mn@ELE not only loads elemene (ELE) into porous Mn nanozymes (Mn NPs) but is also coated with EpCAM-targeting chimeric antigen receptor-engineered 293T cell membranes (CAR-M). Notably, through multiple modifications, the catalytic activity of Mn NPs has been preserved. In vitro studies demonstrated that CAR-M@Mn@ELE selectively targeted and killed 4T1 Cancer cells (EpCAM⁺), while the hydrogel exhibited potent Antibacterial activity against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus). In vivo evaluation using a post-tumor-resection mouse model confirmed that Gel@CAR-M@Mn@ELE significantly suppressed tumor recurrence and prolonged survival. The combination of bioactive components within the hydrogel modulated the immunosuppressive tumor microenvironment, thereby enhancing its immunotherapeutic efficacy. Additionally, in a Bacterial wound Infection model, the hydrogel effectively inhibited Bacterial growth and accelerated wound healing. The Gel@CAR-M@Mn@ELE offers a novel and promising strategy, supported by experimental evidence, for concurrently addressing the critical post-surgical challenges of tumor recurrence and wound Infection.