1. A self-supplied hydrogen peroxide and nitric oxide-generating nanoplatform enhances the efficacy of chemodynamic therapy for biofilm eradication.
- Author
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Jia, Dongxu, Zou, Yi, Zhang, Yuheng, Xu, Hu, Yang, Wei, Zheng, Xinyan, Zhang, Yanxia, and Yu, Qian
- Subjects
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METHICILLIN-resistant staphylococcus aureus , *HYDROGEN peroxide , *HYDROXYL group , *BIOFILMS , *NITRIC oxide - Abstract
[Display omitted] • A nanoplatform capable of both self-supplying H 2 O 2 and generating NO is designed to enhance the effectiveness of chemodynamic therapy for biofilm eradication. • The nanoplatform can respond to the acidic microenvironment within biofilms to trigger a cascade of reactions that produce reactive species such as NO, hydroxyl radicals, and peroxynitrite. • The nanoplatform shows remarkable antibiofilm efficacy by dispersing the biofilm and reducing bacterial viability. Bacterial biofilms present a profound challenge to global public health, often resulting in persistent and recurrent infections that resist treatment. Chemodynamic therapy (CDT), leveraging the conversion of hydrogen peroxide (H 2 O 2) to highly reactive hydroxyl radicals (•OH), has shown potential as an antibacterial approach. Nonetheless, CDT struggles to eliminate biofilms due to limited endogenous H 2 O 2 and the protective extracellular polymeric substances (EPS) within biofilms. This study introduces a multifunctional nanoplatform designed to self-supply H 2 O 2 and generate nitric oxide (NO) to overcome these hurdles. The nanoplatform comprises calcium peroxide (CaO 2) for sustained H 2 O 2 production, a copper-based metal–organic framework (HKUST-1) encapsulating CaO 2 , and l -arginine (l -Arg) as a natural NO donor. When exposed to the acidic microenvironment within biofilms, the HKUST-1 layer decomposes, releasing Cu2+ ions and l -Arg, and exposing the CaO 2 core to initiate a cascade of reactions producing reactive species such as H 2 O 2 , •OH, and superoxide anions (•O 2 –). Subsequently, H 2 O 2 catalyzes l -Arg to produce NO, which disperses the biofilm and reacts with •O 2 – to form peroxynitrite, synergistically eradicating bacteria with •OH. In vitro assays demonstrated the nanoplatform's remarkable antibiofilm efficacy against both Gram-positive Methicillin-resistant Staphylococcus aureus and Gram-negative Pseudomonas aeruginosa , significantly reducing bacterial viability and EPS content. In vivo mouse model experiments validated the nanoplatform's effectiveness in eliminating biofilms and promoting infected wound healing without adverse effects. This study represents a breakthrough in overcoming traditional CDT limitations by integrating self-supplied H 2 O 2 with NO's biofilm-disrupting capabilities, offering a promising therapeutic strategy for biofilm-associated infection. [ABSTRACT FROM AUTHOR] more...
- Published
- 2025
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