Fig 1. DectiSomes are designed to target antifungal drugs specifically to fungal cells.

(A) Coating antifungal drug-loaded liposomes with glycan-binding proteins concentrates drugs on fungal cells. Current antifungal drugs are untargeted (left side). Having no selective affinity for fungal cells over host cells demands higher doses of antifungal drugs to inhibit or kill fungal cells. DectiSomes (right side) are drug-loaded liposomes coated with the glycan recognition domains of glycan-binding host receptors such as dectins. They bind specifically to fungal cell walls and their extracellular matrices within biofilms, which reduce the effective dose needed to clear fungal infections and host toxicity. Infection sites composed of fungal cells with Y or F morphologies are shown. (B) Structure of a DectiSome. One iteration of a DectiSome is an antifungal drug-loaded liposome coated with the glycan recognition domain of a Dectin. We coupled its glycan-binding domain (purple globular structure) to a lipid carrier to make DEC-PEG-DSPE, which is intercalated into the liposomal membrane via the DSPE moiety. Dectin monomers floating in the liposome membrane form dimers as they bind to fungal oligoglycans (yellow sugar moieties). Rhodamine-B-DHPE is intercalated via its DHPE moiety to allow fluorescent monitoring of liposome binding to fungal cells. Amphiphobic antifungal drugs (blue ovoid structure) are positioned within the lipid bilayer of liposomes. Each approximately 100-nm diameter liposome contains approximately 1,500 Dectin monomers, thousands of antifungal drug molecules, and 3,000 rhodamine molecules. DEC, dectin; DHPE, dihexadecanoyl-glycero-phospho-ethanolamine; DSPE, distearoyl-glycero-phospho-ethanolamine; F, filamentous; PEG, poly(ethylene glycol); Y, yeast.