Antibacterial gold nanoclusters: Protamine-coated, enzyme-inhibiting nanoparticles combat drug-resistant bacteria and accelerate wound healing

Antimicrobial resistance (AMR) persists primarily due to the barrier effect of biofilms and the transient bactericidal activity of conventional antimicrobials, creating a demand for antimicrobial strategies independent of AMR mechanisms. To address this critical challenge, this study develops an innovative nanoplatform (Au@PS) by integrating protamine sulfate (PS) with gold nanoclusters. The synthesized Au@PS demonstrates broad-spectrum antimicrobial activity with significantly enhanced efficacy, leveraging the synergistic antimicrobial advantages of gold nanoclusters and PS. Specifically, PS increases the surface charge of gold nanoclusters, strengthening electrostatic adsorption between the nanoplatform and bacteria. This enhanced interaction promotes frequent contact with bacterial cell walls, causing extensive damage—even against methicillin-resistant Staphylococcus aureus (MRSA), which has thicker cell walls, Au@PS maintains strong bactericidal capacity. Once the bacterial cell wall is disrupted, Au@PS penetrates into bacterial cells and induces multiple metabolic disorders via inhibiting various enzymes. Furthermore, Au@PS can penetrate biofilm barriers and suppress biofilm formation (a key contributor to AMR and chronic infections). It also accelerates wound healing in mouse models by facilitating cell proliferation and migration. As a bifunctional material with both antimicrobial and pro-regenerative properties, Au@PS not only treats established wound infections but also prevents infections when applied to wound surfaces in complex wound environments. This nanoplatform thus offers a promising multifunctional alternative for future clinical wound care.