Engineering Gold Nanocage-Grafted Hollow Polydopamine Composites Potentially Boost Nitric Oxide Releasing and Multimodal Synergistic Antimicrobial Therapy

Gas therapy shows significant clinical promise for antimicrobial applications by effectively modulating bacterial activity and suppressing biofilm formation. Nevertheless, the limited gas release efficiency continues to pose a major challenge that compromises its therapeutic effectiveness. Here, we designed and constructed a multilayer nanocomposite (HBAC) using hollow polydopamine (HPDA) as the primary carrier for the nitric oxide (NO) donor N,N'-di-sec-butyl-N,N'-di-nitroso-p-phenylenediamine (BNN6). By grafting gold nanocages (Au NCs) onto its surface, the photothermal conversion efficiency (PCE, η) was significantly enhanced, optimizing the real-time NO release. Furthermore, leveraging the hollow structure and nanoenzyme activity of Au NCs, we encapsulated the antimicrobial agent curcumin (Cur), enabling HBAC to simultaneously activate three synergistic antibacterial modes: gene-like inhibition, photothermal therapy (PTT), and photodynamic therapy (PDT) under near-infrared laser irradiation. This multifunctional platform exhibits exceptional efficacy in suppressing the growth and biofilm formation of diverse Gram-positive and Gram-negative bacteria, including S. epider, E. coli, B. subt, and E. aero, with a bactericidal efficiency exceeding 95%. Our approach offers a promising strategy to enhance gas sterilization efficiency and accelerate the clinical translation of multimodal antimicrobial therapy.