4.8 Article

Visualized Gallium/Lyticase-Integrated Antifungal Strategy for Fungal Keratitis Treatment

期刊

ADVANCED MATERIALS
卷 34, 期 49, 页码 -

出版社

WILEY-V C H VERLAG GMBH
DOI: 10.1002/adma.202206437

关键词

exopolysaccharides degradation; fungal keratitis; gallium; intrinsic metabolic interference; Raman imaging

资金

  1. National Natural Science Foundation of China (NSFC) [81971667]
  2. Fundamental Research Funds for the Zhejiang Provincial Universities, China [2021XZZX034]
  3. Binjiang Institute of Zhejiang University [ZY202205SMKY007]
  4. Key Research and Development Project of Zhejiang Province [2020C03035]

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This study presents lyticase and gallium ions co-integrated nanosystems (MLPGa) that degrade exopolysaccharides and effectively eradicate both planktonic Candida albicans and mature biofilms. The antifungal mechanism involves reactive oxygen species production and metabolic interference of various genes. Real-time visualization of gallium release is achieved through Raman signals generated by the chelation between the nanosystems and gallium ions. The MLPGa-based antifungal strategy demonstrates good biocompatibility and therapeutic effect in a fungal keratitis mouse model.
Fungal keratitis has been one of the common corneal infections that causes blindness, but an effective antifungal strategy remains a challenge. The exopolysaccharides both in the fungal cell walls and biofilms are a key that acts as a permeation barrier to weaken the therapeutic effect of antifungal agents. Herein, lyticase and gallium ions co-integrated nanosystems (MLPGa) are presented that can degrade exopolysaccharides and then effectively eradicate both planktonic Candida albicans and mature biofilms. The potential antifungal mechanism involves reactive oxygen species (ROS) production and metabolic interference of antioxidant-related genes, exopolysaccharide-related genes, iron-ion-utilization-related genes, fungal/biofilm-development-related genes, and virulence genes. Meanwhile, the Raman signals generated by the chelation between the nanosystems and the gallium ions provide a real-time visualization tool to monitor Ga release. Finally, the MLPGa-based antifungal strategy with good biocompatibility achieves a satisfactory therapeutic effect in a fungal keratitis mouse model. This study provides a unique approach to the effective treatment of fungal keratitis in clinical practice.

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