Hyaluronic acid and antimicrobial peptide-modified gold/silver hybrid nanocages to combat bacterial multidrug resistance

Bacterial multidrug resistance is a major challenge for the treatment of infection. In this study, a gold-silver hybrid nanocage (Au/Ag NCs) is designed to conjugated with an antimicrobial peptide (AP) and hyaluronic acid (HA) via Au-S bond and electrostatic adsorption respectively. HA-P(Au/Ag) shows a small size (128 nm), a high efficiency of photothermal conversion, and a good stability. Under near-infrared (NIR) irradiation, HA-P(Au/Ag) effectively kills multidrug resistant bacteria-Acinetobacter baumannii (MDR-AB) by disrupting their inner and outer membrane. A pneumonia model caused by MDR-AB is established in mice. HA-P(Au/Ag) treatment reduces the number of bacterial colonies and inflammation in lung tissues and restores the structure of pulmonary alveoli. HA-P(Au/Ag)/NIR treatment increases the survival rate of pneumonia mice to 100%. Safety evaluation demonstrates that HA-P(Au/Ag) causes little cytotoxicity and hemolysis, and shows neglectable impact to the key indicators of kidney and liver function. To conclude, HA-P(Au/Ag) is a highly efficient and safe strategy that is promising to combat MDR-AB caused infection in vitro and in vivo.