Bacterial Microenvironment-Responsive Fe-Ce6 Nanoparticles Accelerate Infected Wound Healing via In Situ Generation of Nanozyme and Photodynamic Antibacterial Activity

• • Fe-Ce6 NPs exhibit ATP-triggered disassembly with a 671 nm laser-activated Ce6 release, achieving >99.9% (3-log) reduction of S. aureus and E. coli in vitro within 20 min, addressing the need for rapid, broad-spectrum bactericidal action in infected wounds. • • The in situ formed Fe-ATP complex demonstrates POD-like activity with a catalytic efficiency (kcat/Km) of 1.2 × 10^5 M^-1 s^-1 for H2O2 conversion to ·OH, enabling localized ROS generation that minimizes off-target cytotoxicity compared to constitutive nanozymes. • • In vivo murine wound models show 95% wound closure by day 10 with Fe-Ce6 + laser treatment, versus 60% in controls (p < 0.01), and a 4-log reduction in bacterial burden, directly correlating with accelerated healing and reduced inflammation. • • The avalanche effect, driven by ATP released from lysed bacteria, amplifies Fe-ATP formation and Ce6 release, yielding a 2.5-fold increase in ·OH and 1O2 generation after initial bacterial lysis, providing a self-reinforcing mechanism that overcomes the limited efficacy of single-modal therapies.