An alginate-based biomimetic nanozyme metabolic immunomodulator for sensitizing photothermal-immunotherapy in...

The postoperative therapy for breast cancer is significantly restricted by local immunosuppression and the non-healing of infected wounds. We developed a botanical/nanozyme/polysaccharide metabolic immunomodulator (BCZG), using alginate as the primary scaffold, integrating baicalein-loaded carbon nanozyme into a polydopamine-modified alginate hydrogel. In the acidic tumor microenvironment, the BCZG mimicked NOX, OXD, and GSHOx activities, which could deplete NADH/ATP and glutathione to block heat shock protein synthesis and amplify ROS storms for achieving robust immunogenic cell death. Meanwhile, the loaded baicalein as a heat shock protein inhibitor synergistically enhanced PTT sensitivity in conjunction with the energy metabolism-blocking effect of the nanozymes. In the neutral/alkaline wound microenvironment, the BCZG hydrogel switched to catalase- and superoxide dismutase-like activities, scavenging excess ROS, relieving inflammation, and exerting potent antibacterial effects to promote postoperative wound healing. The alginate-based biomimetic nanozyme system disrupted the vicious cycle of wound infection, persistent inflammation, immunosuppressive niche formation, and tumor recurrence. Consequently, it reprogrammed energy metabolism and activated antitumor immunity, offering a novel strategy for postoperative breast cancer treatment.