One-pot engineered zinc-porphyrin nanosheets for enhanced antibacterial therapy and wound repair

Photodynamic therapy (PDT) represents a paradigm shift in antimicrobial strategies, offering distinct advantages over conventional antibiotics, including precise spatiotemporal control, minimal resistance development, and non-invasive operation. However, the clinical translation of conventional photosensitizers is impeded by poor aqueous solubility, aggregation-induced deactivation, and suboptimal bactericidal efficiency. To address these challenges, we engineered two-dimensional (2D) zinc-porphyrin metal-organic framework (MOF) nanosheets through a coordination-driven self-assembly approach, where tetrakis (4-carboxyphenyl) porphyrin (TCPP) serves dual functions as both photosensitizing ligand and structural building block. Through controlled coordination assembly between Zn²⁺ nodes and TCPP linkers, we achieved ultrathin nanosheets with exceptional photophysical properties and microenvironment-responsive behavior. The nanosheets exhibit pH-dependent dissociation, with rapid degradation and photosensitizer release occurring at pH 5.5 while maintaining stability at physiological pH. Comprehensive characterization revealed that the nanosheets significantly enhance intersystem crossing efficiency, yielding a singlet oxygen quantum yield higher than the free TCPP. In vitro studies demonstrated potent antibacterial activity against Escherichia coli, methicillin resistant Staphylococcus aureus (MRSA), and Staphylococcus aureus, achieving reduction upon 660 nm irradiation while showing excellent biocompatibility with mouse embryonic fibroblast cells. In vivo mouse wound infection models revealed bacterial reduction in infected wounds while accelerating re-epithelialization compared to untreated controls. This work establishes a new paradigm for antimicrobial nanomaterials that simultaneously address pathogen elimination and tissue regeneration through precisely engineered metal-organic architectures.