Engineering "Yin-Yang" Ag/AgCl-Polymer Nanotherapeutic for Tunable Silver Ion Release With Improved In Vivo...

The rapid insurgence of antimicrobial resistance poses a critical threat to global health exacerbated by the dwindling supply of the effective arsenal of therapeutics. Nanomaterials provide alternative strategies by enabling novel antimicrobials that evade pathogens' intrinsic defense systems; yet their translation is constrained by complex synthesis, limited activity, and suboptimal invivo biocompatibility and efficacy. Silver-based systems rely on the release of Ag⁺ ions; however, achieving a controlled flux of Ag⁺ with therapeutic efficacy, stability, and biocompatibility remains a challenge. To circumvent this, we report a water-soluble polymeric biphasic Ag/AgCl nanocomposite (PBNP) synthesized via in situ nanoprecipitation and partial reduction by an inherently antibacterial quaternized thiolated chitosan polymer without using any external reducing agent. PBNP enables the controlled release of Ag⁺ ions over 10 days, demonstrating broad-spectrum antimicrobial activity, including the clearance of intracellular methicillin-resistant S. aureus (MRSA) infection, suppression of virulence factors and disruption of polymicrobial biofilm (MRSA and C. albicans), an outcome not achieved by conventional silver-based solutions. Additionally, PBNP reduced > 99.999% MRSA burden in murine skin infection without inducing dermal toxicity or genotoxicity when biocompatibility was assessed in zebrafish, emphasizing its potential as a therapeutic.