Liu Zeyu, Li Minying, Xie Qiulin, Liu Yinghui, Huang Jialin, Zeng Qin, Li Xipeng, Rao Kexiang, Ning Juewei, Zhao Minghai, Li Bin, Li Feng, Liu Haiyang, Zhou Sitong, Shu Bowen, Yang Bin, Zheng Judun, Liao Yuhui
Molecular Diagnosis and Treatment Center for Infectious Diseases, Dermatology Hospital, Southern Medical University, Guangzhou, PR China.
Institute for Engineering Medicine, Kunming Medical University, Kunming, PR China.
Nat Commun. 2025 Jul 15;16(1):6499. doi: 10.1038/s41467-025-61519-1.
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-CN) 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-CN-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.
真菌生物膜作为自身产生的抵抗抗真菌剂和免疫防御的细胞外聚合物，是治疗失败和反复感染的主要原因。因此，根除真菌生物膜对于实现有效治疗至关重要。本研究通过设计超声-光双响应纳米杂化物（UCNP@CR），开发了一种协同活性氧（ROS）增强策略来根除白色念珠菌生物膜。该系统将表面包覆氮化碳（g-CN）的掺铥上转换纳米颗粒（UCNPs）与聚吡啶钌配合物（Ru）光敏剂相结合。在治疗过程中，致密的真菌生物膜在超声刺激下可有效疏松，同时超声触发UCNP@CR产生ROS，共同促进生物膜的不可逆破坏和光敏剂的向内渗透。此外，UCNP@CR表现出很强的真菌黏附性，而其g-CN介导的Ru在近红外光照射下增强的金属-配体电荷转移（MLCT）过程会放大ROS的产生，从而有效根除真菌生物膜。作为体内实验证据，UCNP@CR在超声-光刺激下对免疫抑制雄性小鼠的真菌生物膜感染伤口具有优异的抗真菌疗效。这些发现确立了超声辅助、ROS增强的协同策略作为对抗真菌生物膜感染的一种有前景的方法，并为管理其他生物膜相关传染病提供了不同的视角。
