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

作者：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, Yuhui Liao · 发表于：Nature Communications · 年份：2025 · DOI：10.1038/s41467-025-61519-1 · 被引用次数：55 · 研究领域：Nanoplatforms for cancer theranostics、Photodynamic Therapy Research Studies、Photoacoustic and Ultrasonic Imaging

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 inf...