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

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dc.contributor.authorGhosh, Chandradhishen
dc.contributor.authorVarela-Aramburu, Silviaen
dc.contributor.authorEldesouky, Hassan E.en
dc.contributor.authorSalehi Hossainy, Shararehen
dc.contributor.authorSeleem, Mohamed N.en
dc.contributor.authorAebischer, Tonien
dc.contributor.authorSeeberger, Peter H.en
dc.contributor.departmentBiomedical Sciences and Pathobiologyen
dc.date.accessioned2021-04-21T17:16:00Zen
dc.date.available2021-04-21T17:16:00Zen
dc.date.issued2021-03-18en
dc.description.abstractInfections by intracellular pathogens cause significant morbidity and mortality due to lack of efficient drug delivery. Amphotericin B, currently used to treat leish maniasis and cryptococcosis, is very toxic and cannot eradicate intracellular Cryptococcus neoformans (C. neoformans). Glycosylated gold nanoparticles are water dispersible and biocompatible with very little toxici ty. 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 mu g 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.en
dc.description.notesThe authors thank the Max-Planck Society for generous financial support. The authors would also like to thank Eva Settels, Reinhild Dunnebacke, and Rona Pitschke for technical support. The authors would also like to thank Bruna Mara Silva Seco and Dr. Michael Downey for their meticulous scrutiny of the manuscript.; Open access funding enabled and organized by Projekt DEAL.en
dc.description.sponsorshipMax-Planck SocietyMax Planck SocietyFoundation CELLEXen
dc.format.mimetypeapplication/pdfen
dc.identifier.doihttps://doi.org/10.1002/adtp.202000293en
dc.identifier.eissn2366-3987en
dc.identifier.other2000293en
dc.identifier.urihttp://hdl.handle.net/10919/103071en
dc.language.isoenen
dc.rightsCreative Commons Attribution 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.titleNon-Toxic Glycosylated Gold Nanoparticle-Amphotericin B Conjugates Reduce Biofilms and Intracellular Burden of Fungi and Parasitesen
dc.title.serialAdvanced Therapeuticsen
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten
dc.type.dcmitypeStillImageen

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