Syringeable hyaluronic acid-based hydrogel co-loaded with Cisplatin and MSA-2 for enhanced ovarian cancer chemoimmunotherapy

Low immunogenicity and a prevailing immunosuppressive tumor microenvironment (TME) remain major bottlenecks for ovarian cancer immunotherapy. While plati-num-based chemotherapy can trigger antitumor immunity via immunogenic cell death (ICD), its clinical efficacy is often hampered by the intrinsic immunosuppressive milieu and insufficient drug accumulation at the tumor site following systemic administration. To address these challenges, we fabricated a syringeable hyaluronic acid-based hydrogel co-loaded with Cisplatin (CDDP) and STING agonist MSA-2 (CDDP/MSA-2@Gel) for enhanced localized chemoimmunotherapy. The sustained local release of CDDP and MSA-2 synergistically boost stimulator of interferon genes (STING) pathway activation, thereby eliciting potent type-I-IFN-driven systemic antitumor immune responses and alleviating the immunosuppressive TME. In vivo studies demonstrated that CDDP/MSA-2@Gel treatment significantly inhibits tumor growth in murine ovarian cancer models without systemic toxicity.Collectively, our designed CDDP/MSA-2@Gel represents a safe and potent strategy for enhanced synergistic chemoimmunotherapy, offering significant potential for clinical translation in the treatment of ovarian cancer.