A dual-asymmetry hemostatic Janus hydrogel patch inhibits postoperative recurrence and metastasis of triple-negative breast cancer by suppressing COX-2/PGE2 axis

Surgical resection combined with chemotherapy remains the standard clinical intervention for triple-negative breast cancer (TNBC). However, the elevated expression of COX-2/PGE 2 , often exacerbated by chemotherapeutic agents, is significantly associated with high postoperative recurrence and metastasis. Tailored for the TNBC postoperative setting, we developed a photopolymerizable, dual-asymmetric hemostatic Janus hydrogel patch (DJ-Patch) based on the synergistic pharmacodynamic rationale of gambogic acid (GA) and celecoxib (CXB) pairing. The DJ-Patch exhibits a stratified bilayer configuration comprising a rapid-release layer (5% GelMA) encapsulating GA, juxtaposed with an extended-release layer (10% GelMA/2.5% PEGNB) containing the selective COX-2 inhibitor CXB. In vitro study corroborated this differential release modality, revealing asymmetric kinetics wherein GA achieved ∼20% release at 8 h escalating to greater than 60% by day 3, whereas CXB demonstrated ∼10% release at 8 h and ∼30% by day 3. In vivo release profiles further substantiated these findings, demonstrating that CXB exhibited a 2-fold prolonged release duration relative to GA. The asymmetric adhesive design, featuring a high-adhesion interface manifesting adhesion strength 12.5-fold superior to GelMA alone, facilitated rapid intraoperative hemostasis with clotting time reduced to 160 s versus 440 s in untreated controls, and effected efficacious wound sealing as validated in a mouse liver laceration model. In an orthotopic 4T1-Luc TNBC resection model, the DJ-Patch achieved 86% survival, complete tumor clearance by day 7, and suppressed lung metastasis through sustained COX-2/PGE 2 axis inhibition, Treg cell reduction, and remodeled the immunosuppressive tumor microenvironment (TME). Collectively, this integrated platform offers a promising strategy for comprehensive TNBC postsurgical management.