Anaerobic bio-reduction ignites persistent photothermal conversion in misaligned porphyrin supramolecular assembly...

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 Escherichia coli (E. coli) 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.