Engineered Nanoparticles Enhance Photodynamic Inactivation Against the WHO Fungal Priority Pathogens. A Systematic Review

Fungal infections pose a significant global health concern, prompting the WHO to prioritize fungi needing novel therapies. Photodynamic inactivation (PDI), which uses light, a photosensitizer (PS), and oxygen to produce oxidative stress, has shown promising results against fungi. Engineered nanoparticles (NPs) have emerged as a promising ally to enhance PDI. This systematic review examined the combined effects of PDI and NPs on the WHO's priority fungal pathogens. After screening Embase, Pubmed, Scopus, and Web of Science, ten studies were selected based on criteria including consistent NP characterization, PDI protocol, and a focus on critical and high priority fungi. Most studies targeted Candida albicans, with only one of them on Fusarium keratoplasticum. Only 4 studies reported the effects of PDI mediated by NPs on biofilms. Nanostructures applied included metallic, superparamagnetic iron oxide, micelle, and polymeric NPs. Findings indicate that i-) NPs can enhance the solubility of PSs by carrying hydrophobic compounds; ii-) NPs may improve the chemical stability of PSs avoiding aggregation, which could reduce the PS performance; iii-) NPs can be engineered to reduce the required PS concentration for effective fungal elimination, and iv-) Metallic NPs can improve the photophysical properties of PSs, such as enhancing the generation of reactive oxygen species by localized surface plasmon resonance. Further research is needed to extend these findings beyond in vitro conditions.