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April 4, 2026Journal of Nanobiotechnology3 citationsOpen Access

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

YCYuyu CuiQNQiang NiuZLZhaojia Li

Key Points

  • The research aims to develop a novel nanozyme using copper and rhein for better antibacterial therapy and tissue regeneration in bacterial infections.
  • Developed Cu-Rhein nanozyme via hydrothermal process.
  • Evaluated antibacterial activity against MRSA and PA using reactive oxygen species production.
  • Studied the mechanism behind the 'Activation-Exhaustion' effect on bacteria.
  • Conducted in vivo experiments with dual-delivery of treatment for infected wounds and pneumonia.
  • Assessed biosafety and toxicity profiles.
  • Cu-Rhein showed significant antibacterial effects against multidrug-resistant bacteria.
  • Nanozyme promoted tissue repair through enhanced collagen deposition and angiogenesis.
  • Demonstrated negligible toxicity, supporting safety for medical applications.

Abstract

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.

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Cite This Study

Cui et al. (2026) studied this question.

synapsesocial.com/papers/69d0adc2659487ece0fa44d4https://doi.org/10.1186/s12951-026-04308-2
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