Promotion of reactive oxygen species activated by nanosilver surface engineering for resistant bacteria-infected skin tissue therapy

Nanosilver has been regarded as a promising alternative to traditional antibiotics for fighting pathogen-associated infections due to its efficacy toward a broad spectrum of pathogens. However, bacterial resistance to nanosilver has emerged recently. In this contribution, a surface engineering strategy based on N-halamine chemistry to address bacterial resistance to nanosilver was proposed. Using 1,3-dichloro-5,5-dimethylhydantoin (DCDMH) as an N-halamine source, AgCl nanodots were deposited on the surface of Ag nanowires (Ag NWs) via in situ redox reaction to prepare AgCl-on-Ag NWs. After in vitro and in vivo tests, AgCl-on-Ag NWs effectively inactivated two antibiotic-resistant bacteria, ampicillin-resistant Escherichia coli (AREC) and methicillin-resistant Staphylococcus aureus (MRSA) with the minimum bactericidal concentration (MBC) as low as 10 μg·ml −1 and exhibited good biosafety against normal cells. The experimental and theoretical tests demonstrated that AgCl-on-Ag NWs worked on AREC and MASA by generating high level of reactive oxygen species under visible light irradiation, coupled with the sustained Ag + ion release. Meanwhile, the antibacterial mechanism of AgCl-on-Ag NWs against MRSA was verified at the gene level by transcriptome analysis (RNA sequencing). Moreover, the full-thickness defect model verified that AgCl-on-Ag NWs reduced inflammatory cell infiltration and dramatically accelerated wound healing. This work provides a synergistic mechanism based on nanosilver surface engineering to eradicate the resistant bacteria that can alleviate drug resistance and develop an innovative approach for the treatment of bacterial infections.