Facile Synthesis of Self-Targeted Zn2+-Gallic acid Nanoflowers for Specific Adhesion and Elimination of Gram-Positive Bacteria

Transition metal ions are served as disinfectant thousand years ago. However, the in vivo antibacterial application of metal ions is strongly restricted due to its high affinity with proteins and lack of appropriate bacterial targeting method. Herein, for the first time, Zn2+-gallic acid nanoflowers (ZGNFs) are synthesized by a facile one-pot method without additional stabilizing agents. ZGNFs are stable in aqueous solution while can be easily decomposed in acidic environments. Besides, ZGNFs can specifically adhere onto Gram-positive bacteria, which is mediated by the interaction of quinone from ZGNFs and amino groups from teichoic acid of Gram-positive bacteria. ZGNFs exhibit high bactericidal effect toward various Gram-positive bacteria in multiple environments, which can be ascribed to the in situ Zn2+ release on bacterial surface. Transcriptome studies reveal that ZGNFs can disorder basic metabolic processes of Methicillin-resistant Staphylococcus aureus (MRSA). Moreover, in a MRSA-induced keratitis model, ZGNFs exhibit long-term retention in the infected corneal site and prominent MRSA elimination efficacy due to the self-targeting ability. This research not only reports an innovative method to prepare metal-polyphenol nanoparticles, but also provides a novel nanoplatform for targeted delivery of Zn2+ in combating Gram-positive bacterial infections.

Automated summary

Transition metal ions have been used as disinfectants for thousands of years, but their in vivo antibacterial application is limited due to their high affinity with proteins and lacking appropriate bacterial targeting methods. In this study, Zn2+-gallic acid nanoflowers (ZGNFs) were synthesized for the first time using a facile one-pot method without additional stabilizing agents. ZGNFs are stable in aqueous solution but can be easily decomposed in acidic environments. They exhibit high bactericidal effect on Gram-positive bacteria by specifically adhering to them, and the in situ Zn2+ release on the bacterial surface is the main reason for this effect. The research also demonstrates the potential of ZGNFs as a targeted delivery system for combating Gram-positive bacterial infections.