Copper-rhein nanozymes induce bacterial activation-exhaustion death for the treatment of bacterial pneumonia and infected wounds.

Bacterial pneumonia and chronic wounds are life-threatening conditions affecting the elderly that are often refractory to preventive measures because of drug-resistance infections and biofilm formation. In order to overcome these clinical challenges, Cu2+ with the natural product rhein were coordinated to achieve a multifunctional nanozyme for antibacterial therapy and tissue regeneration. The tactic augmented the catalytic stability and biocompatibility of the nanozyme and at the same time improved the solubility and bioavailability of rhein. Cu-Rhein (Cu-Rh) prepared through a hydrothermal process exhibited a homogenous rod-shaped morphology and both the peroxidase-like and glutathione peroxidase-like catalytic activity. These characteristics facilitated effective production of reactive oxygen species under infection-like conditions, leading to broad-spectrum antibacterial activity against MRSA and PA. Mechanistic experiments had shown that Cu-Rh activated bacterial ribosomal function, caused futile protein synthesis, and accelerated intracellular energy depletion, resulting in an "Activation-Exhaustion" antibacterial mechanism. Besides, rhein enhanced antioxidative and anti-inflammatory effects, promoting collagen deposition, angiogenesis, and tissue repair. Dual-delivery approach involving topical application of sprays to infected wounds and aerosol delivery of treatment to cases with acute pulmonary infections, achieved highly efficient bacterial clearance and tissue protection in vivo. Biosafety studies confirmed negligible toxicity. This study found out that Cu-Rh are safe and effective nonantibiotic therapeutic platforms capable of treating multidrug-resistant bacterial infections while promoting tissue regeneration.