Non-Toxic Glycosylated Gold Nanoparticle-Amphotericin B Conjugates Reduce Biofilms and Intracellular Burden of Fungi and Parasites

Abstract

Infections by intracellular pathogens cause significant morbidity and mortality due to lack of efficient drug delivery. Amphotericin B, currently used to treat leishmaniasis and cryptococcosis, is very toxic and cannot eradicate intracellular Cryptococcus neoformans (C. neoformans). Glycosylated gold nanoparticles are water dispersible and biocompatible with very little toxicity. While amphotericin B is insoluble in water at neutral pH, conjugates of amphotericin B and ultra-small gold nanoparticles (AuNP) are better dispersible in water. Amphotericin B conjugated glycosylated gold nanoparticles (AmpoB@AuNP) are more efficacious in treating both extracellular and intracellular forms of Leishmania mexicana (L. mexicana) than amphotericin B alone. In addition, AmpoB@AuNP are effective in reducing C. neoformans biofilms by 80% and intracellular C. neoformans burden by >90%. Furthermore, AmpoB@AuNP are not haemolytic at 50 µg mL−1 and are significantly less toxic to murine macrophages than amphotericin B. Ultra-small AuNPs are attractive delivery agents to treat intracellular infections and AmpoB@AuNP may be useful for treating C. neoformans infections in immunocompromised patients.