Ru-complex functionalized fungus-adherent upconversion nanosystem for NIR photodynamic anti-fungal therapy

Fungal infections pose a severe global health threat, exacerbated by limited treatment options and increasing drug resistance. Ruthenium (Ru) complex based photodynamic therapy (PDT) presents a promising alternative that circumvents drug resistance, but its application has been constrained by poor tissue light penetration and limited accumulation within pathogens. To address these challenges, we developed a drug-loading core-shell nanosystem based on upconversion nanoparticles (UCNPs), designated as UCNP@dmSiO 2 -Ru, which integrates Yb/Tm-doped UCNPs with a polypyridine ruthenium (II) photosensitizer. Upon 980 nm irradiation, the UCNPs emit visible light that activates the ruthenium complex through energy transfer, resulting in localized singlet oxygen generation. In vitro , this nanoparticle could adhere to fungal cells, and demonstrated potent antifungal activity. In murine wound infection model, topical application followed by near-infrared light irradiation significantly accelerated the wound healing and reduced fungal burden, with no observable toxicity. This work provides a fungus-adherent PDT nanosystem with NIR-activation, overcoming the tissue penetration limitation and offering a promising strategy for treating deep-seated fungal infections.