Targeted Delivery of Antifungal Liposomes to .

Mucormycosis (a.k.a. zygomycosis) is an often-life-threatening disease caused by fungi from the ancient fungal division Mucoromycota. Globally, there are nearly a million people with the disease. spp., and () in particular, are responsible for most of the diagnosed cases. Pulmonary, rhino-orbito-cerebral, and invasive mucormycosis are most effectively treated with amphotericin B (AmB) and particularly with liposomal formulations (e.g., AmBisome). However, even after antifungal therapy, there is still a 50% mortality rate. Hence, there is a critical need to improve therapeutics for mucormycosis. Targeting AmB-loaded liposomes (AmB-LLs) with the pathogen receptor Dectin-1 (DEC1-AmB-LLs) to the beta-glucans expressed on the surface of and lowers the effective dose required to kill cells relative to untargeted AmB-LLs. Because Dectin-1 is an immune receptor for infections and may bind it directly, we explored the Dectin-1-mediated delivery of liposomal AmB to . DEC1-AmB-LLs bound 100- to 1000-fold more efficiently to the exopolysaccharide matrix of germlings and mature hyphae relative to AmB-LLs. DEC1-AmB-LLs delivering sub-micromolar concentrations of AmB were an order of magnitude more efficient at inhibiting and/or killing than AmB-LLs. Targeted antifungal drug-loaded liposomes have the potential to improve the treatment of mucormycosis.