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<p>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 <i>Candida albicans</i> biofilms by designing ultrasound-light dual-responsive nanohybrids (UCNP@CR). The system integrates thulium-doped upconversion nanoparticles (UCNPs) with carbon nitride-coated surfaces (g-C<sub>3</sub>N<sub>4</sub>) 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-C<sub>3</sub>N<sub>4</sub>-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.</p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年7月15日

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  • 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

摘要

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.