Multifunctional EGCG@ZIF-8 Nanoplatform with Photodynamic Therapy/Chemodynamic Therapy Antibacterial Properties Promotes Infected Wound Healing

Damaged skin is susceptible to invasion by harmful microorganisms, especially <i>Staphylococcus aureus</i> and <i>Escherichia coli</i>, which can delay healing. Epigallocatechin-3-gallate (EGCG) is a natural compound known for effectively promoting wound healing and its potent anti-inflammatory effects. However, its application is limited due to its susceptibility to oxidation and isomerization, which alter its structure. The use of zeolitic imidazolate framework-8 (ZIF-8) can effectively tackle these issues. This study introduces an oxygen (O₂) and hydrogen peroxide (H₂O₂) self-supplying ZIF-8 nanoplatform designed to enhance the bioavailability of EGCG, combining photodynamic therapy (PDT) and chemodynamic therapy (CDT) to improve antibacterial properties and ultimately accelerate wound healing. For this purpose, EGCG and indocyanine green (ICG), a photosensitizer, were successively integrated into a ZIF-8, and coated with bovine serum albumin (BSA) to enhance biocompatibility. The outer layer of this construct was further modified with manganese dioxide (MnO₂) to promote CDT and calcium peroxide (CaO₂) to supply H₂O₂ and O₂, resulting in the final nanoplatform EGCG-ICG@ZIF-8/BSA-MnO₂/CaO₂ (EIZBMC). In <i>in vitro</i> experiments under 808 nm laser, EIZBMC exhibited synergistic antibacterial effects through PDT and CDT. This combination effectively released reactive oxygen species (ROS), which mediated oxidative stress to inhibit the bacteria. Subsequently, in a murine model of wound infection, EIZBMC not only exerted antibacterial effects through PDT and CDT but also alleviated the inflammatory condition and promoted the regeneration of collagen fibers, which led to accelerated wound healing. Overall, this research presents a promising approach to enhancing the therapeutic efficacy of EGCG by leveraging the synergistic antibacterial effects of PDT and CDT. This multifunctional nanoplatform maximizes EGCG's anti-inflammatory properties, offering a potent solution for promoting infected wound healing.