Reactive oxygen species-mediated CuRuOX@HA hybrid nanozymes for multidrug-resistant bacterial infections with synergistic photothermal therapy

Abstract

Drug-resistant bacterial infections pose a serious threat to human life and health, especially multidrug-resistant bacterial infections are difficult to treat with currently available antibiotics. A number of evidences showed that reactive oxygen species (ROS) and photothermal therapy (PTT) can easily kill drug-resistant bacteria while they have not developed resistance to drugs. Inspired by good stability and high catalytic activity of nanozymes and in order to construct versatile nanozymes, the therapy of ROS was integrated with PTT. This study prepared a ROS-mediated copper-ruthenium oxide (CuRuO_X) hybrid nanozyme (CuRuO_X@HA) modified with hyaluronic acid (HA). Via hybridization, CuRuO_X@HA NPs not only have good ROS generation capability but also possess excellent photothermal performance with a photothermal conversion efficiency of 62.7%. Thus, the CuRuO_X@HA nanozyme achieves the synergistic treatment of drug-resistant bacterial infections using PTT/chemodynamic therapy (CDT). Moreover, under the mediated action of ROS, CuRuO_X@HA can effectively deplete glutathione, which is a nutrient of bacteria, and hence, the nanozyme can impede the growth of drug-resistant bacteria. In vivo, this hybrid nanozyme efficiently removes MRSA from infected wounds and speeds up wound healing with few adverse effects. The CuRuO_X@HA hybrid nanozyme is a viable candidate for clinical treatment due to its strong antibacterial activities and good biosafety.