Postsurgical wound management and prevention of triple-negative breast cancer recurrence with a pryoptosis-inducing, photopolymerizable hydrogel

Surgical removal remains the predominant treatment strategy for triple-negative breast cancer (TNBC). However, risks that include high locoregional recurrence and remote metastasis threaten patient survival and quality of life after surgery. In this study, a hydrogel based on poly (ethylene glycol) dimethacrylate and sericin methacryloyl was fabricated by photopolymerization to fill the resection cavity and prevent recurrence. The obtained hydrogel exhibited mechanical properties compatible with breast tissue and facilitated postsurgical wound management by promoting tissue regeneration. The DNA methylation inhibitor decitabine (DEC) and poly (lactic-co-glycolic acid)-encapsulated phytochemical gambogic acid (GA) were loaded into the hydrogel. The as-prepared hydrogel promoted fast release of DEC and sustained release of GA, leading to gasdermin E-mediated tumor cell pyroptosis and activating antitumor immune responses. Inducing postsurgical tumor cell pyroptosis inhibited local tumor recurrence and lung metastasis. While the dual-drug-loaded hydrogel system cured less than half of tumor-bearing mice, the cured mice survived for over half a year. These findings indicate that our hydrogel system is an excellent biocompatible platform for postsurgical TNBC therapy.