Surface-Charge-Switchable and Size-Transformable Thermosensitive Nanocomposites for Chemo-Photothermal Eradication of Bacterial Biofilms in Vitro and in Vivo

The appearance of multidrug-resistant bacteria and their biofilms presents a serious threat to modern medical systems. Herein, we fabricated a novel gold-nanorod-based chemo-photothermal-integrated antimicrobial platform with surface-charge-switchable and near-infrared (NIR)-induced size-transformable activities that show an enhanced killing efficiency against methicillin-resistant Staphylococcus aureus ( MRSA ) in both planktonic and biofilm phenotypes. The nanocomposites are prepared by in situ copolymerization using N -isopropyl acrylamide (NIPAM), acrylic acid (AA), and N -allylmethylamine (MAA) as monomers on the surfaces of gold nanorods (GNRs). Ciprofloxacin (CIP) is loaded onto polymer shells of nanocomposites with a loading content of 9.8%. The negatively charged nanocomposites switch to positive upon passive accumulation at the infectious sites, which promotes deep biofilm penetration and bacterial adhesion of the nanoparticles. Subsequently, NIR irradiation triggers the nanocomposites to rapidly shrink in volume, further increasing the depth of biofilm penetration. The NIR-triggered, ultrafast volume shrinkage causes an instant release of CIP on the bacterial surface, realizing the synergistic benefits of chemo-photothermal therapy. Both in vitro and in vivo evidence demonstrate that drug-loaded nanocomposites could eradicate clinical MRSA biofilms. Taken together, the multifunctional chemo-photothermal-integrated antimicrobial platform, as designed, is a promising antimicrobial agent against MRSA infections.