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Abstract
Fungal infections account for approximately 2.5 million deaths globally each year and billions of dollars in healthcare costs annually in just the United States. However, only three primary classes of antifungal drugs exist to treat these infections. Issues with these classes of antifungal drugs include organ toxicity and rising levels of drug resistance. The polyene amphotericin B (AmB), which targets ergosterol in the fungal cell membrane, has been described as the “gold standard” of antifungal treatments due to its broad spectrum of activity. However, it also has an affinity for cholesterol, thus leading to severe side effects that limit its use. The liposomal formulation of AmB was designed to address these issues; although this was an improvement over the original formulation, the toxicity concerns are still a prevalent limiting factor. To address these issues, our research group created a targeted antifungal liposome (DectiSome), in which the liposome’s surface is coated with Dectin immune receptors that specifically recognize fungal cells. Dectin-1 and Dectin-2 DectiSomes have improved targeting efficacy over untargeted liposomes in vitro against the clinically relevant fungal pathogens Aspergillus fumigatus, Candida albicans, and Cryptococcus neoformans. This work focuses on evaluating additional uses for this novel technology. The findings presented here demonstrate that Dectin-1 DectiSomes have improved targeting efficacy in vitro against Rhizopus delemar, a common causative agent of mucormycosis. A novel Dectin-3 DectiSome has improved targeting efficacy in vitro against R. delemar, C. albicans, and C. neoformans. A biotinylated Dectin-1-coated liposome has potential as a fungal cell pull-down tool to facilitate additional analyses.