Phytochemical-Loaded Thermo-responsive Liposome for Synergistic Treatment of Methicillin-Resistant Staphylococcus aureus Infection

The ever-increasing emergence and prevalence of multidrug-resistant bacteria accelerate the desire for the development of new antibacterial strategies. Although antibacterial phytochemicals are a promising approach for long-term treatment of resistant bacteria, their low antibacterial activity and poor solubility hinder their practical applications. Here, the natural antibacterial compound sanguinarine (SG) together with gallic acid–ferrous coordination nanoparticles (GA-Fe(II) NPs) was encapsulated in a near-infrared (NIR)-activated thermo-responsive liposome. By virtue of the photothermal effect of GA-Fe(II) NPs, the nanoplatform released SG on demand upon NIR irradiation. Additionally, the heat can boost the Fenton reaction triggered by GA-Fe(II) NPs to generate hydroxyl radicals and perform sterilization. By coupling with photothermal therapy, chemodynamic therapy, and SG-based pharmacotherapy, the platform showed enhanced antibacterial efficiency and an antibiofilm effect toward methicillin-resistant Staphylococcus aureus and reduced the risk of developing new bacterial resistance. This antibacterial system displayed excellent antibacterial activity in a methicillin-resistant S. aureus-caused skin abscess, demonstrating its potential clinical application. Moreover, transcription analysis clarified that the platform achieved a synergistic antibacterial effect by attacking the cell membrane, inducing energy metabolism disorder, inhibiting nucleic acid synthesis, etc. The developed NIR-controlled phytochemical-loaded platform offers new possibilities for killing antibiotic-resistant bacteria and avoiding bacterial resistance, making it contributory in the fields of anti-infective therapy and precision medicine.