Targeted Delivery of Antifungal Liposomes to Rhizopus delemar .
Quanita J ChoudhurySuresh AmbatiZachary A LewisRichard B MeagherPublished in: Journal of fungi (Basel, Switzerland) (2022)
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. Rhizopus spp., and R. delemar ( R. oryzae, R. arrhizus ) 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 Aspergillus fumigatus and Candida albicans lowers the effective dose required to kill cells relative to untargeted AmB-LLs. Because Dectin-1 is an immune receptor for R. delemar infections and may bind it directly, we explored the Dectin-1-mediated delivery of liposomal AmB to R. delemar . DEC1-AmB-LLs bound 100- to 1000-fold more efficiently to the exopolysaccharide matrix of R. delemar 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 R. delemar than AmB-LLs. Targeted antifungal drug-loaded liposomes have the potential to improve the treatment of mucormycosis.
Keyphrases
- candida albicans
- drug delivery
- cancer therapy
- biofilm formation
- induced apoptosis
- mass spectrometry
- pulmonary hypertension
- risk assessment
- cardiovascular events
- cell death
- cystic fibrosis
- risk factors
- staphylococcus aureus
- human health
- bone marrow
- mesenchymal stem cells
- newly diagnosed
- endoplasmic reticulum stress
- high resolution mass spectrometry
- cerebral ischemia
- cell cycle arrest
- adverse drug