Infection microenvironment-responsive composites based on a Ag(I) complex for targeted antimicrobial treatment

To address always-on Ag⁺ release of Ag(I) complexes for antimicrobial treatment, infection microenvironment-responsive composites with high antimicrobial efficiency and on-demand Ag⁺ release were constructed by coating hyaluronic acid (HA) or an Fe(III)-tannic acid complex (Fe(III)-TA) on a deliberately designed silver complex (1) with a high silver content of 46.76%. The targeted Ag⁺ leaching to eradicate bacteria was dependent on stimuli-responsive coating decomposition. Infection microenvironment cues, i.e. hyaluronidase (HAase) and acidity, were used as endogenous triggers, and the wrapped complex 1 acted as a carrier for antimicrobial Ag⁺. This smart design can avoid the use of additional carriers for the antimicrobial agents required in previous approaches and reduces the side effects of degradation in the infection microenvironment. Complex 1 was characterized by single-crystal X-ray diffraction as a 1D chain assembled from Ag₁₂ clusters. It exhibits effective broad-spectrum antimicrobial activities with low minimum inhibition concentrations (MICs) originating from high Ag⁺ content. Under non-infection conditions, Ag⁺ release ratios of 1@HA and 1@Fe(III)-TA were suppressed significantly to 14.99% and 3.31%, respectively. In a simulated infection microenvironment (1 wt% HAase or pH 5.5), the composites exhibited stimulus-switched coating disassembly, leading to increased Ag⁺ release ratios of 59.26% and 23.92%, respectively. The moderate pH-induced Ag⁺ release of 1@Fe(III)-TA was attributed to partial cleavage of Fe-OH of Fe(III)-TA at pH 5.5, which was verified by the pH-dependent Ag⁺ release of 1@Fe(III)-TA. The stimuli-responsive coating deconstruction and the antimicrobial performance of the two composites were confirmed by measurements of water contact angles, zeta potentials, inhibition zones, and MICs. 1@Fe(III)-TA displayed more obvious acid-triggered performance for P. aeruginosa and carbapenem-resistant E. coli due to their stronger acid-producing characteristics. The successful integration of an efficient antimicrobial Ag(I) complex with infection microenvironment-responsive coatings highlights its potential as a facile strategy for on-demand antimicrobial treatment of targeted bacterial infection.