MoS2 nanoflowers loaded with L-Arg and activated by IR780 for NO release in a cascade manner for elimination of drug-resistant bacteria and biofilms

Multidrug-resistant (MDR) bacterial infections remain a critical public health concern worldwide, with conventional antibacterial strategies presenting limitations such as inconsistent target localization, suboptimal therapeutic efficiency, and progressive antimicrobial resistance development. Nitric oxide (NO), a bioactive molecule, exhibits potent antibacterial effects, resulting in the emergence of NO-based gas therapy as a promising and innovative therapeutic strategy. However, these therapies present the principal challenge of effective NO delivery, owing to its short half-life and limited diffusion capacity. Hence, this study aimed to develop AI‑molybdenum disulfide (L-Arg/IR780@MoS 2 ) nanoflowers (NFs) employing L-arginine (L-Arg) as an endogenous NO precursor and MoS 2 as a dual carrier for L-Arg and IR780 iodide (IR780). Following near-infrared irradiation during photodynamic therapy, generated reactive oxygen species initiated an oxidation cascade for L-Arg-to-NO conversion. The produced NO, in combination with photothermal therapy, modulated the bacterial microenvironment. This significantly altered the expression of key genes in MDR bacteria associated with nucleotide metabolism and biofilm formation, thereby effectively disrupting biofilms and suppressing bacterial growth. Furthermore, the AI-MoS 2 NFs exhibited notable ancillary therapeutic benefits, including anti-inflammatory activity, enhanced re-epithelialization, increased collagen deposition, and angiogenesis modulation, which collectively accelerated wound healing. Altogether, the findings of this study present a synergistic therapeutic strategy designed to address the dual challenges posed by bacterial biofilms and antimicrobial resistance.