A Metal-Based Heterojunction for Controlled Release of Multiple Cations and Reactive Oxygen Species Inhibiting Multidrug-Resistant Bacteria In Vitro and In Vivo.

Spherical heterojunction nanocomposite materials are utilized to treat wound infections caused by drug-resistant bacteria by generating reactive oxygen species (ROS) and multiple cations (multiple inorganic or organic ions with positive points). However, there is an ongoing debate on the relative contributions of ROS and multiple cations toward antibacterial activity. In this study, the CuFe2O4/Cu@PEI/Ag (ZPA) nanocomposites were synthesized for releasing abundant•O2-,•OH, Fe3+, Cu2+, Ag+, and polyethylenimine (PEI), and studied the contribution of the released ions to the bacteriostatic activity against drug sensitive Staphylococcus aureus (ATCC25923) and drug-resistant S. aureus (ATCC43360). The results revealed that the antibacterial activity is attributed in the following order: multiple cations >•O2->•OH > single cation. The antibacterial mechanism of the material involved leakage of the cytoplasmic content by damaging the bacterial cell wall, and the alteration of the secondary structure of the cell wall by multiple cations bound to the bacterial cell wall via electrostatic attraction. By healing drug-resistant S. aureus-induced wound infection and completely eliminating bacterial burden after 11 days, in addition, ZPA also effectively polarized M1 type macrophages to M2 type in vivo to promote wound healing. Thus, our findings elucidate that multiple cations occupy an important position on the antibacterial properties of composite nanomaterials. Moreover, The ZPA represent a promising strategy for addressing drug-resistant S. aureus-induced wound infections.