Cuprous oxide–demethyleneberberine nanospheres for single near-infrared light-triggered photoresponsive-enhanced enzymatic synergistic antibacterial therapy

Abstract

In this work, novel cuprous oxide–demethyleneberberine (Cu₂O–DMB) nanomaterials are successfully synthesized for photoresponsive-enhanced enzymatic synergistic antibacterial therapy under near-infrared (NIR) irradiation (808 nm). Cu₂O–DMB has a spherical morphology with a smaller nanosize and positive ζ potential, can trap bacteria through electrostatic interactions resulting in a targeting function. Cu₂O–DMB nanospheres show both oxidase-like and peroxidase-like activities, and serve as a self-cascade platform, which can deplete high concentrations of GSH to produce O₂˙⁻ and H₂O₂, then H₂O₂ is transformed into ˙OH, without introducing exogenous H₂O₂. At the same time, Cu₂O–DMB nanospheres become photoresponsive, producing ¹O₂ and having an efficient photothermal conversion effect upon NIR irradiation. The proposed mechanism is that the generated ROS (O₂˙⁻, ˙OH and ¹O₂) and hyperthermia can have synergetic effects for killing bacteria. Moreover, hyperthermia is not only beneficial for destroying bacteria, but also effectively enhances the efficiency of ˙OH production and accelerates GSH oxidation. Upon NIR irradiation, Cu₂O–DMB nanospheres exhibit excellent antibacterial ability against methicillin-resistant Staphylococcus aureus (MRSA) and ampicillin-resistant Escherichia coli (AREC) with low cytotoxicity and bare bacterial resistance, destroy the bacterial membrane causing an efflux of proteins and disrupt the bacterial biofilm formation. Animal experiments show that the Cu₂O–DMB + NIR group can efficiently treat MRSA infection and promote wound healing. These results suggest that Cu₂O–DMB nanospheres are effective materials for combating bacterial infections highly efficiently and to aid the development of photoresponsive enzymatic synergistic antibacterial therapy.