Silicon(IV) Phthalocyanine-Functionalized Hyaluronic Acid for Photodynamic Eradication of Methicillin-Resistant Staphylococcus aureus Infections

Methicillin-resistant Staphylococcus aureus (MRSA) poses a severe threat in bacterial wound infections, driving the need for effective nonantibiotic strategies. Antimicrobial photodynamic therapy (aPDT) using phthalocyanines (Pcs) as photosensitizers is promising but often hampered by their poor aqueous solubility and aggregation-induced quenching. Herein, we report the design and synthesis of a highly water-soluble photosensitizer (PcSi-HA) by the axial conjugation of silicon(IV) phthalocyanine (PcSi) molecules to the polymer backbone of hyaluronic acid (HA). The bulky and hydrophilic HA chain effectively suppresses the detrimental π–π stacking of PcSi molecules, significantly enhancing both solubility and reactive oxygen species (ROS) generation upon 650 nm light irradiation. PcSi-HA achieved 99% antibacterial efficacy against both S. aureus and MRSA at an ultralow concentration of 2 μg/mL, whereas negligible antibacterial activity was observed in the absence of irradiation. Among the ROS generated by PcSi-HA, the mechanistic studies reveal that hydrogen peroxide (H2O2) serves as the dominant bactericidal species. To facilitate practical application, PcSi-HA was physically loaded onto a polyimide (PI) nanofibrous membrane (prepared via electrospinning of a poly(amic acid) (PAA) precursor followed by thermal imidization) to fabricate a flexible photodynamic wound dressing (PI-PcSi). In a murine model of MRSA-infected wounds, the PI-PcSi dressing, under light irradiation, effectively eliminated bacteria and accelerated wound healing by promoting collagen deposition. This work presents a facile strategy for developing advanced phthalocyanine-based biomaterials via polysaccharide functionalization, offering a potent and biocompatible platform for combating drug-resistant bacterial infections.