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Eradicating fungal biofilm-based infections by ultrasound-assisted semiconductor sensitized upconversion photodynamic therapy

Zeyu Liu, Minying Li, Qiulin Xie, Yinghui Liu, Jialin Huang, Qin Zeng, Xipeng Li, Kexiang Rao, Juewei Ning, Minghai Zhao, Bin Li, Feng Li, Haiyang Liu, Sitong Zhou, Bowen Shu (), Bin Yang (), Judun Zheng () and Yuhui Liao ()
Additional contact information
Zeyu Liu: Southern Medical University
Minying Li: Southern Medical University
Qiulin Xie: Southern Medical University
Yinghui Liu: Southern Medical University
Jialin Huang: Southern Medical University
Qin Zeng: Kunming Medical University
Xipeng Li: Kunming Medical University
Kexiang Rao: Southern Medical University
Juewei Ning: Southern Medical University
Minghai Zhao: Southern Medical University
Bin Li: Ningxia Medical University
Feng Li: South China University of Technology
Haiyang Liu: South China University of Technology
Sitong Zhou: The First People’s Hospital of Foshan
Bowen Shu: Southern Medical University
Bin Yang: Southern Medical University
Judun Zheng: Southern Medical University
Yuhui Liao: Kunming Medical University

Nature Communications, 2025, vol. 16, issue 1, 1-17

Abstract: Abstract Fungal biofilms, as self-produced extracellular polymeric substances that resist antifungal agents and immune defense, represent a major cause of treatment failure and recurrent infections. Therefore, it is of great importance to eradicate fungal biofilms to achieve efficient therapy. This study develops a synergistic reactive oxygen species (ROS)-enhanced strategy to eradicate Candida albicans biofilms by designing ultrasound-light dual-responsive nanohybrids (UCNP@CR). The system integrates thulium-doped upconversion nanoparticles (UCNPs) with carbon nitride-coated surfaces (g-C3N4) and polypyridine ruthenium complex (Ru) photosensitizers. In treatment, the dense fungal biofilm can be effectively loosened under ultrasound stimulation while ultrasound simultaneously triggers ROS production of UCNP@CR, collectively promoting irreversible destruction of biofilm and inward penetration of photosensitizer. Moreover, UCNP@CR exhibits strong fungal adhesion, while its g-C3N4-mediated enhanced metal-to-ligand charge transfer (MLCT) process of Ru under near-infrared light irradiation amplifies ROS generation, which leads to efficient eradication of fungal biofilms. As in vivo experimental evidence, UCNP@CR exhibits excellent antifungal efficacy in treating fungal biofilm-infected wounds in immunosuppressed male mice under ultrasound-light stimulation. These findings establish the ultrasound-assisted, ROS-enhanced synergistic strategy as a promising approach against fungal biofilm infections and provide diverse perspective for managing other biofilm-related infectious diseases.

Date: 2025
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DOI: 10.1038/s41467-025-61519-1

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