An Adhesive Immune-Stimulating Multifunctional Hydrogel for Potent Tumor Chemoimmunotherapy and Postoperative Wound Healing Promotion

Surgical excision is the first choice for clinical cancer therapy. However, major challenges, such as postoperative tumor recurrence and unsatisfactory wound healing after surgery, remain. In this study, an adhesive hydrogel is developed as a multifunctional platform for antitumor chemoimmunotherapy and postoperative wound treatment. The hydrogel adheres firmly to diverse tissues and degrades within 4 weeks in vivo with good histocompatibility. The immune-stimulating hydrogel ((DOX+R837@HN)@Gel) is fabricated by encapsulating doxorubicin (DOX) and imiquimod-loaded HSA nanoparticles (R837@HNs) into the hydrogel. When combined with immune checkpoint blockade (ICB) therapy, intratumorally administering (DOX+R837@HN)@Gel exhibits markedly enhanced systemic antitumor efficacy and strengthened antitumor immunity. For tumor surgical resection, (DOX+R837@HN)@Gel can adhere to the wounds and effectively prevents tumor recurrence and achieves long-term immune memory with ICB therapy. Moreover, the hydrogel achieves rapid hemostasis and promotes wound healing after treating surgical wound models. Therefore, this multifunctional hydrogel has great significance for clinical postsurgical cancer treatment. A tissue-adhesive multifunctional hydrogel is developed as a drug depot for simultaneous tumor chemoimmunotherapy, hemostasis and wound healing. After encapsulating doxorubicin (DOX) and imiquimod (R837), the drug-loaded hydrogel combined with anti-programmed cell death-1 (anti-PD-1) exhibits only 10% tumor recurrence in a mice model of resected melanoma. Meanwhile, the hydrogel also promotes postsurgical hemostasis and wound healing in hepatic hemorrhage and full-thickness skin wound model, respectively.image