Single Continuous Near-Infrared Laser-Triggered Photodynamic and Photothermal Ablation of Antibiotic-Resistant Bacteria Using Effective Targeted Copper Sulfide Nanoclusters.

Abstract

The emergence of antibiotic-resistant bacterial strains has made conventional antibiotic therapies less efficient. The development of a novel nanoantibiotic approach for efficiently ablating such bacterial infections is becoming crucial. Herein, a collection of poly(5-(2-ethyl acrylate)-4-methylthiazole-g-butyl)/copper sulfide nanoclusters (PATA-C4@CuS) was synthesized for efficient capture and effective ablation of levofloxacin-resistant Gram-negative and Gram-positive bacteria upon tissue-penetrable near-infrared (NIR) laser irradiation. In this work, we took advantage of the excellent photothermal and photodynamic properties of copper sulfide nanoparticles (CuSNPs) upon NIR laser irradiation and thiazole derivative as a membrane-targeting cationic ligand toward bacteria. The conjugated nanoclusters could anchor the bacteria to trigger the bacterial aggregation quickly and efficiently kill them. These conjugated nanoclusters could significantly inhibit levofloxacin-resistant Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, and Bacillus amyloliquefaciens at 5.5 μg/mL under NIR laser irradiation (980 nm, 1.5 W cm-2, 5 min), which suggested that the heat and reactive oxygen species (ROS) generated from the irradiated CuSNPs attached to bacteria were effective in eliminating and preventing the regrowth of the bacteria. Importantly, the conjugated nanoclusters could promote healing in bacteria-infected rat wounds without nonspecific damage to normal tissue. These findings highlight the promise of the highly versatile multifunctional nanoantibiotics in bacterial infection.