Aiming for a bull’s-eye: Targeting antifungals to fungi with dectin-decorated liposomes

Abstract

Globally, there are several million individuals with life-threatening invasive fungal diseases such as candidiasis, aspergillosis, cryptococcosis, Pneumocystis pneumonia (PCP), and mucormycosis. The mortality rate for these diseases generally exceeds 40%. Annual medical costs to treat these invasive fungal diseases in the United States exceed several billion dollars. In addition to AIDS patients, the risks of invasive mycoses are increasingly found in immune-impaired individuals or in immunosuppressed patients following stem cell or organ transplant or implantation of medical devices. Current antifungal drug therapies are not meeting the challenge, because (1) at safe doses, they do not provide sufficient fungal clearance to prevent reemergence of infection; (2) most become toxic with extended use; (3) drug-resistant fungal isolates are emerging; and (4) only one new class of antifungal drugs has been approved for clinical use in the last 2 decades. DectiSomes represent a novel design of drug delivery to drastically increase drug efficacy. Antifungals packaged in liposomes are targeted specifically to where the pathogen is, through binding to the fungal cell walls or exopolysaccharide matrices using the carbohydrate recognition domains of pathogen receptors. Relative to untargeted liposomal drug, DectiSomes show order of magnitude increases in the binding to and killing of Candida albicans, Cryptococcus neoformans, and Aspergillus fumigatus in vitro and similarly improved efficacy in mouse models of pulmonary aspergillosis. DectiSomes have the potential to usher in a new antifungal drug treatment paradigm.

Artificial nanovesicles for dsRNA delivery in spray‐induced gene silencing for crop protection

“…Liposomes have been extensively researched for their applications in clinical contexts (Tenchov et al ., 2021), in fact, they have been utilized for drug delivery to human fungal pathogens (Meagher et al ., 2021; Voltan et al ., 2016) and are able to transit across the fungal cell wall (Walker et al ., 2018). Here, we provide the first demonstration that lipid‐based nanovesicles can also be used in agricultural contexts, to deliver dsRNA to plant pathogens.…”

Artificial nanovesicles for dsRNA delivery in spray induced gene silencing for crop protection

“…Liposomes have been extensively researched for their applications in clinical contexts 47 , in fact, they have been utilized for drug delivery to human fungal pathogens [51][52] and are able to transit across the fungal cell wall 53 . Here, we provide the first demonstration that lipid-based nanovesicles can also be used in agricultural contexts, to deliver dsRNA to plant pathogens.…”

Nanoliposomes as Drug Delivery Systems for Antifungal Therapy

“…There have been several attempts to improve the targetability of NLPs to treat fungal infections. Meagher et al (2021) have created a novel drug delivery system (DDS) with a particular affinity to fungal pathogens. They're based on Dectin-decorated NLPs (Decti-Somes).…”

“…Additionally, LPs are only moderately effective at crossing the blood-brain barrier, and the effects of coating them with dectins are yet to be addressed experimentally. Decti-Somes can recognize pathogens such as Aspergillus, Candida, Pneumocystis, Cryptococcus, and Mucor species that are the main causes of global fungal infections, making them promising pan-antifungal agents [55].…”