MoS ₂ /Au–Ag@PEG nanosheets with plasmonic coupling effect-enhanced NIR-II photothermal therapy and silver ion release for combined treatment of MRSA infection

The evolution of bacterial resistance to antibiotics has resulted in a global public health crisis, necessitating the development of novel antibiotic-independent antimicrobial strategies. In this study, MoS₂/Au-Ag@PEG nanosheets (MAAP NSs) were prepared <i>via</i> sequential deposition of gold and silver nanoparticles onto MoS₂ nanosheets (MoS₂ NSs), which were then used for the treatment of methicillin-resistant <i>Staphylococcus aureus</i> (MRSA) infections. Compared to MoS₂ NSs, MAAP NSs exhibit a significantly enhanced near-infrared region II (NIR-II) absorption at 1064 nm (a 7.51-fold increase), and the photothermal conversion efficiency improves by 50.7%, reaching 19.9%. Theoretical simulations reveal that the plasmonic coupling effect between adjacent Au-Ag nanoparticles (Au-Ag NPs) on the surface of MAAP NSs leads to the formation of hot spots and significantly enhances NIR-II light absorption, thereby improving the NIR-II photothermal performance. Moreover, the release of silver ions (Ag⁺) can be effectively controlled by NIR laser irradiation. <i>In vitro</i> experimental results show that, upon NIR-II laser (1064 nm) exposure, MAAP NSs can effectively eliminate established MRSA biofilms with a bacterial inactivation efficiency of 99.992%. Notably, benefiting from the superior tissue penetration of the NIR-II laser, MAAP NSs exhibit potent therapeutic efficacy against both superficial wound infection and subcutaneous implant-associated MRSA biofilm infection in mouse models. <i>In vivo</i> results demonstrate that, under NIR-II laser stimulation, MAAP NSs can not only effectively kill 99.95% of MRSA in infected wounds and accelerate wound healing, but also remove MRSA biofilms from subcutaneous implant surfaces, achieving a 99.92% bacterial reduction. This work presents a novel strategy for designing NIR-II responsive antibacterial nanoagents based on plasmonic coupling effects in two-dimensional (2D) nanosheets and provides a promising solution for the treatment of antibiotic-resistant bacterial infections.