Dectin-2-Targeted Antifungal Liposomes Exhibit Enhanced Efficacy

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Abstract
Invasive fungal diseases caused by Candida albicans , Cryptococcus neoformans , and Aspergillus fumigatus have mortality rates ranging from 10 to 95%. Individual patient costs may exceed $100,000 in the United States. All antifungals in current use have serious limitations due to host toxicity and/or insufficient fungal cell killing that results in recurrent infections. Few new antifungal drugs have been introduced in the last 2 decades. Hence, there is a critical need for improved antifungal therapeutics. By targeting antifungal-loaded liposomes to α-mannans in the extracellular matrices secreted by these fungi, we dramatically reduced the effective dose of drug. Dectin-2-coated liposomes loaded with amphotericin B bound 50- to 150-fold more strongly to C. albicans , C. neoformans , and A. fumigatus than untargeted liposomes and killed these fungi more than an order of magnitude more efficiently. Targeting drug-loaded liposomes specifically to fungal cells has the potential to greatly enhance the efficacy of most antifungal drugs.
Funding Information
  • HHS | NIH | NIH Office of the Director (R21 AI144498)
  • HHS | NIH | NIH Office of the Director (UL1TR002378)
  • HHS | NIH | NIH Office of the Director (1R01AI140719)
  • American Cancer Society (RSG-14-184-01-DMC)
  • University of Georgia

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