Yanwen Zhou,Haozhuo Lei,Meng Wang,Yanbin Shi,Zhaohui Wang
Bactericidal nanomedicines often suffer from a complicated design and insufficient intrinsic inhibitory efficacy. Herein, novel anti-bacterial copper telluride (CuTe) nano-clusters are reported, featuring superior bactericidal efficiency, facile preparation, and unique mechanism. These nanoparticles, well dispersable in water, resembled grape clusters with rough surfaces. The CuTe nano-grape clusters exhibited ultra-high sterilization efficacy at ultra-low concentration, particularly for Gram-negative bacteria, and were more potent than conventional anti-microbial nanoparticles. Also, the grape clusters effectively inhibited the bacterial biofilm development. Further investigation revealed the synergized mechanisms of reactive oxygen species (ROS) generation and glutathione (GSH) depletion. Interestingly, electron microscopy revealed that the grape clusters served as bacterial hunters by tightly adhering to bacterial surfaces. The bacteria subsequently suffered from the leakage of various intracellular components including nucleic acid, proteins, and potassium. Most encouragingly, CuTe drastically reduced bacterial number in a mouse model with lethal intraperitoneal infection and increased the mouse survival rate to 90%. This finding could inspire the development of highly potent bactericidal inorganic formulations with simplified structure, multiple antibacterial mechanisms, and promising application potential.
Pseudomonas aeruginosa ( P. aeruginosa ) infections present a grave threat to immunocompromised individuals, particularly those with cystic fibrosis due to the development of bacterial biofilms. In this study, we engineered self-assembling chitosan-ceftazidime nanoparticles (CSCE) capable of effectively penetrating biofilms and eradicating P. aeruginos a. The CSCE nanoparticles were synthesized through ionic cross-linking, combining negatively charged ceftazidime with positively charged chitosan, resulting in uniform nanoparticles measuring approximately 40 nm in diameter, exhibiting high dispersity and excellent biocompatibility. Remarkably, these nanoparticles exhibited significant inhibition of P. aeruginosa growth, reduced pyocyanin production, and diminished biofilm formation, achieving a maximum inhibition rate of 22.44%. Furthermore, in vivo investigations demonstrated enhanced survival in mice with abdominal P. aeruginosa infection following treatment with CSCE nanoparticles, accompanied by reduced levels of inflammatory cytokines Interleukin-6 (125.79 ± 18.63 pg/mL), Interleukin-17 (125.67 ± 5.94 pg/mL), and Tumor Necrosis Factor-α (135.4 ± 11.77 pg/mL). Critically, mice treated with CSCE nanoparticles showed no presence of bacteria in the bloodstream following intraperitoneal P. aeruginosa infection. Collectively, our findings highlight the potential of these synthesized nanoparticles as effective agents against P. aeruginosa infections.
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