Size-Tuned Gold Nanoparticles for Treating Lethal Bacterial Pneumonia

Abstract

Targeted delivery and low toxicity are key considerations in the development of nanomaterials. Herein, we report a strategy to realize accumulation of antibacterial gold nanoparticles (GNPs) in the lungs via regulating particle size. We prepare two types of 3-amino-1,2,4-triazole-5-thiol (ATT)-modified GNPs (A-GNPs) with distinct sizes: small A-GNPs (A-sGNPs) and large A-GNPs (A-lGNPs). The A-sGNPs preferentially accumulate in the lungs, instead of in the liver or kidneys. This targeting ability lowered their toxicity to the liver and kidneys. In contrast, the A-lGNPs exhibit the opposite distribution profile. The A-GNPs especially A-sGNPs show potent antibacterial effects against multidrug-resistant (MDR) Gram-negative bacteria. In a mouse model of pneumonia induced by MDR Pseudomonas aeruginosa (P.a), A-sGNPs achieve a 100% bacterial clearance rate in lung tissue and a 100% animal survival rate, demonstrating ideal therapeutic effects and low systemic toxicity in a size-dependent manner. Our work paves the way for developing nanomaterials with improved bioactivity and ameliorated side effects by tuning particle size, offering broad potential for biomedical applications.