Self-organization of zinc ions with a photosensitizer in vivo for enhanced antibiofilm and infected wound healing

Antimicrobial materials have been developed to combat bacteria more effectively and promote infected wound healing. However, it is widely recognized that the potential toxic effects and complexity of the synthesis process hinder their practical applications. In this work, we introduced a strategy for fighting bacteria and promoting wound healing caused by Staphylococcus epidermidis (S. epidermidis) infection by the self-combination of Zn²⁺ and clinically applied 5-aminolevulinic acid hydrochloride (ALA) in the microbes. The clinical ALA could target and accumulate in the biofilm as well as contribute to the low-dose Zn²⁺ penetrating the biofilm due to the self-organized formation of Zn protoporphyrin IX in situ. Upon exposing to a 635 nm laser, the self-combination of ALA and Zn²⁺ significantly inhibited and eliminated the S. epidermidis biofilm via a synergistic biofilm eradication mechanism that enhanced photodynamic inactivation and aggravated cell wall/membrane disruption. In addition, the combination of ALA and Zn²⁺ could accelerate wound repair and reduce inflammatory response without causing cytotoxicity. The proposed strategy in this study illustrates the clinical prospects of eradicating biofilms and repairing infected wounds and demonstrates good biocompatibility towards infectious diseases.