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Cu-Single Atoms/Clusters-Nanoenzymes Trigger and Integrate Tandem Effect to Synchronously Boost Antifungal and
Mengyang Zhao1, Xiwen Geng1, Qin Zeng1
1Henan Eye Hospital, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, Zhengzhou, P.R. China.
Abstract:
Fungal keratitis (FK) is an extremely blinding infectious ocular surface disease. Clinically, there are three major challenges in the topic drug treatment of FK: poor corneal permeability, poor antifungal effect, and inability to simultaneously reduce the inflammation accompanying the infection. In this work, atomically dispersed Cu-N4 and Cu nanoclusters is designed loaded on the a small-sized positively charged CDs (denoted as Cu-SA/NC@CDs) is designed to fabricate Cu-Needs. The Cu-Needs exhibited excellent corneal permeability, which could can temporarily open the tight connections between corneal cells. More importantly, Cu-Needs achieve rapid fungal elimination and eradication through energy depletion in fungus in the early stage of FK. Subsequently, Cu-Needs effectively eliminated ROS and alleviated the inflammation in cornea tissue. This work proposes a strategy for the whole-process intervention of fungal keratitis by regulating the microenvironment of single-atom centers and nanoclusters through a tandem effect and enhancing catalytic activity. Conclusively, the excellent biosafety (biocompatibility, irritancy, ocular local toxicity and systemic toxicity) made Cu-Needs a great potential strategy in clinical treatment of FK and other serious infectious diseases.
Insights
This study introduces Cu-Needs, a novel treatment for fungal keratitis (FK). Cu-Needs enhance corneal penetration, rapidly eliminate fungi, and reduce inflammation, offering a promising strategy for treating this blinding eye infection.
Area of Science:
- Ophthalmology
- Materials Science
- Infectious Diseases
Background:
- Fungal keratitis (FK) is a severe infectious ocular disease with significant challenges in drug treatment.
- Current treatments face issues with poor corneal permeability, limited antifungal efficacy, and inadequate inflammation control.
Purpose of the Study:
- To develop a novel therapeutic agent, Cu-Needs, for effective whole-process intervention of fungal keratitis.
- To address the limitations of existing FK treatments by enhancing corneal permeability, antifungal activity, and anti-inflammatory effects.
Main Methods:
- Atomically dispersed Cu-N4 and Cu nanoclusters were loaded onto small-sized, positively charged carbon dots (Cu-SA/NC@CDs) to create Cu-Needs.
- The ability of Cu-Needs to improve corneal permeability, eliminate fungi via energy depletion, scavenge reactive oxygen species (ROS), and reduce inflammation was evaluated.
Main Results:
- Cu-Needs demonstrated excellent corneal permeability by temporarily opening tight junctions between corneal cells.
- Rapid fungal elimination was achieved through energy depletion in fungi during the early stages of FK.
- Cu-Needs effectively reduced ROS and alleviated corneal inflammation, showing significant therapeutic potential.
Conclusions:
- Cu-Needs represent a promising strategy for the comprehensive management of fungal keratitis.
- The designed material exhibits excellent biosafety, including biocompatibility and low toxicity, making it suitable for clinical applications in FK and other infectious diseases.
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