Temporally Programmed and Laser-Triggered Immunomodulatory Hydrogel Enables Synergistic Wound Healing and Prevention of Postoperative Tumor Recurrence

Surgery remains the predominant therapeutic option for patients with colorectal cancer. However, residual microscopic lesions and the immunosuppressive microenvironment considerably elevate the risk of postoperative tumor recurrence. Additionally, intestinal fistulas are the most common complication of surgery and severely impair the quality of life for patients. Current postoperative adjuvant therapies are limited by their systemic toxicity, inadequate immunomodulatory potential, and poor tumor targeting capacity, resulting in limited therapeutic efficacy. To address these challenges, a multifunctional hydrogel system that combined temporally programmed and laser-triggered release of specific drugs for integrated wound repair, precision tumor ablation, and the prevention of postoperative tumor recurrence was developed herein. A Pluronic F127-chitosan hydrogel scaffold was synthesized and coloaded with curcumin and thermosensitive liposomes (PR-Lip) encapsulating R848-loaded mesoporous polydopamine (MPDA). Following in situ implantation at the surgical site, the temperature responsiveness and adhesive properties of the hydrogel prevent the formation of intestinal fistulas. The preferential release of curcumin promotes wound healing and inhibits the recruitment of immunosuppressive cells, thereby alleviating local immunosuppression in an early postoperative stage. Subsequent laser irradiation triggers the release of MPDA and R848 from PR-Lip, enabling localized ablation of residual tumors, initiating potent T-cell-mediated immune responses, and reversing the immunosuppressive tumor microenvironment. This study presents a novel and comprehensive postoperative treatment strategy with the potential capacity to achieve 40% tumor remission rates, thereby advancing the development of intelligent and functionally integrated adjuvant therapies for the postoperative treatment of solid tumors.