Construction of an Infection-Inflammation Microenvironment-Regulating Nano-antimicrobial Agent and Application in the Treatment of Burn Wounds Complicated with Multidrug-Resistant Staphylococcus aureus Infection

Burn wounds are highly susceptible to bacterial colonization, particularly by multidrug-resistant pathogens, which often result in refractory infections, excessive inflammation, and delayed healing. Herein, we report the rational design and construction of a multifunctional nano-antimicrobial agent, designated mPB@PHMB, through the co-assembly of mesoporous Prussian blue (mPB) with the polymer polyhexamethylene biguanide (PHMB). The resultant nanocomposite integrates potent antibacterial activity with the capacity to modulate the inflammatory microenvironment. Notably, mPB@PHMB exhibited pronounced bactericidal efficacy against methicillin-resistant Staphylococcus aureus (MRSA). Benefiting from the intrinsic multi-enzyme-mimetic activities of mPB, the nanocomposite efficiently scavenged intracellular reactive oxygen species, thereby alleviating oxidative stress-induced cellular injury. Transcriptomic profiling and protein analyses revealed that mPB@PHMB markedly suppressed the NF-κB pathway activation, attenuated lipopolysaccharide-induced M1 macrophage polarization, and reduced the production of pro-inflammatory cytokines. Biocompatibility assessments demonstrated negligible acute cytotoxicity toward skin fibroblasts and no overt toxicity in healthy C57BL/6 mice, underscoring the favorable safety profile of mPB@PHMB. Furthermore, in a murine model of MRSA-infected burn wounds, topical treatment with mPB@PHMB reduced the bacterial burden by approximately 90%. Concurrently, treatment with mPB@PHMB substantially decreased the proportion of M1-polarized macrophages, suppressed the expression of inflammatory cytokines, and alleviated the inflammatory milieu within the wound bed, thereby accelerating tissue repair and wound closure. Collectively, these findings establish mPB@PHMB as a promising nano-therapeutic platform that synergistically couples antimicrobial action with immunomodulatory functions, offering a robust and translatable strategy for the management of burn wounds complicated by multidrug-resistant bacterial infection.