Anaerobic bio-reduction ignites persistent photothermal conversion in misaligned porphyrin supramolecular assembly for infected wound regeneration

To address the dual challenges of antibiotic resistance and microbial dysbiosis caused by non-selective photothermal therapy, we engineered an intelligent nanosystem (TPPS₄-Ca) achieving specific recognition and localized photothermal eradication by pathogens. The innovative out-of-plane coordination between Ca²⁺ and anionic porphyrin (TPPS₄) constructs redox-responsive self-assemblies, which not only suppresses the common self-quenching effect of porphyrin aggregation but also significantly enhances the electrostatic targeting toward negatively charged bacteria. Moreover, within the hypoxic microenvironment of facultative anaerobes, TPPS₄-Ca undergoes selective reduction to phlorin/chlorin species with exceptional near-infrared (NIR) photothermal conversion efficiency and operational stability (negligible performance decay over 30 days). The system demonstrates strain selectivity, showing 99.9 % inhibition against facultative anaerobes while exhibiting negligible activity toward commensal aerobes. In rat-infected wound models, TPPS₄-Ca enables precise clearance of <i>Escherichia coli (E. coli)</i> through localized photothermia therapy while accelerating wound closure. Comprehensive biosafety assessments confirm high biocompatibility at cellular and systemic levels. This molecular assembly strategy establishes a promising pathway for developing bacteria-responsive selective photothermal therapeutics with enhanced long-cycling performance.