Ceragenin-Coated Non-Spherical Gold Nanoparticles as Novel Candidacidal Agents

Background: Infections caused by <i>Candida</i> spp. have become one of the major causes of morbidity and mortality in immunocompromised patients. Therefore, new effective fungicides are urgently needed, especially due to an escalating resistance crisis. Methods: A set of nanosystems wit...

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Autores principales:	Karol Skłodowski, Sylwia Joanna Chmielewska, Joanna Depciuch, Piotr Deptuła, Ewelina Piktel, Tamara Daniluk, Magdalena Zakrzewska, Michał Czarnowski, Mateusz Cieśluk, Bonita Durnaś, Magdalena Parlińska-Wojtan, Paul B. Savage, Robert Bucki
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	<i>Candida</i> spp. ceragenins CSA-13 CSA-44 CSA-131 gold nanoparticles Pharmacy and materia medica RS1-441
Acceso en línea:	https://doaj.org/article/d86f711d7372420690b08ae7e10514a9
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spelling	oai:doaj.org-article:d86f711d7372420690b08ae7e10514a92021-11-25T18:42:12ZCeragenin-Coated Non-Spherical Gold Nanoparticles as Novel Candidacidal Agents10.3390/pharmaceutics131119401999-4923https://doaj.org/article/d86f711d7372420690b08ae7e10514a92021-11-01T00:00:00Zhttps://www.mdpi.com/1999-4923/13/11/1940https://doaj.org/toc/1999-4923Background: Infections caused by <i>Candida</i> spp. have become one of the major causes of morbidity and mortality in immunocompromised patients. Therefore, new effective fungicides are urgently needed, especially due to an escalating resistance crisis. Methods: A set of nanosystems with rod- (AuR), peanut- (AuP), and star-shaped (AuS) metal cores were synthesized. These gold nanoparticles were conjugated with ceragenins CSA-13, CSA-44, and CSA-131, and their activity was evaluated against <i>Candida</i> strains (<i>n</i> = 21) through the assessment of MICs (minimum inhibitory concentrations)/MFCs (minimum fungicidal concentrations). Moreover, in order to determine the potential for resistance development, serial passages of <i>Candida</i> cells with tested nanosystems were performed. The principal mechanism of action of Au NPs was evaluated via ROS (reactive oxygen species) generation assessment, plasma membrane permeabilization, and release of the protein content. Finally, to evaluate the potential toxicity of Au NPs, the measurement of hemoglobin release from red blood cells (RBCs) was carried out. Results: All of the tested nanosystems exerted a potent candidacidal activity, regardless of the species or susceptibility to other antifungal agents. Significantly, no resistance development after 25 passages of <i>Candida</i> cells with AuR@CSA-13, AuR@CSA-44, and AuR@CSA-131 nanosystems was observed. Moreover, the fungicidal mechanism of action of the investigated nanosystems involved the generation of ROS, damage of the fungal cell membrane, and leakage of intracellular contents. Notably, no significant RBCs hemolysis at candidacidal doses of tested nanosystems was detected. Conclusions: The results provide rationale for the development of gold nanoparticles of rod-, peanut-, and star-shaped conjugated with CSA-13, CSA-44, and CSA-131 as effective candidacidal agents.Karol SkłodowskiSylwia Joanna ChmielewskaJoanna DepciuchPiotr DeptułaEwelina PiktelTamara DanilukMagdalena ZakrzewskaMichał CzarnowskiMateusz CieślukBonita DurnaśMagdalena Parlińska-WojtanPaul B. SavageRobert BuckiMDPI AGarticle<i>Candida</i> spp.cerageninsCSA-13CSA-44CSA-131gold nanoparticlesPharmacy and materia medicaRS1-441ENPharmaceutics, Vol 13, Iss 1940, p 1940 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	<i>Candida</i> spp. ceragenins CSA-13 CSA-44 CSA-131 gold nanoparticles Pharmacy and materia medica RS1-441
spellingShingle	<i>Candida</i> spp. ceragenins CSA-13 CSA-44 CSA-131 gold nanoparticles Pharmacy and materia medica RS1-441 Karol Skłodowski Sylwia Joanna Chmielewska Joanna Depciuch Piotr Deptuła Ewelina Piktel Tamara Daniluk Magdalena Zakrzewska Michał Czarnowski Mateusz Cieśluk Bonita Durnaś Magdalena Parlińska-Wojtan Paul B. Savage Robert Bucki Ceragenin-Coated Non-Spherical Gold Nanoparticles as Novel Candidacidal Agents
description	Background: Infections caused by <i>Candida</i> spp. have become one of the major causes of morbidity and mortality in immunocompromised patients. Therefore, new effective fungicides are urgently needed, especially due to an escalating resistance crisis. Methods: A set of nanosystems with rod- (AuR), peanut- (AuP), and star-shaped (AuS) metal cores were synthesized. These gold nanoparticles were conjugated with ceragenins CSA-13, CSA-44, and CSA-131, and their activity was evaluated against <i>Candida</i> strains (<i>n</i> = 21) through the assessment of MICs (minimum inhibitory concentrations)/MFCs (minimum fungicidal concentrations). Moreover, in order to determine the potential for resistance development, serial passages of <i>Candida</i> cells with tested nanosystems were performed. The principal mechanism of action of Au NPs was evaluated via ROS (reactive oxygen species) generation assessment, plasma membrane permeabilization, and release of the protein content. Finally, to evaluate the potential toxicity of Au NPs, the measurement of hemoglobin release from red blood cells (RBCs) was carried out. Results: All of the tested nanosystems exerted a potent candidacidal activity, regardless of the species or susceptibility to other antifungal agents. Significantly, no resistance development after 25 passages of <i>Candida</i> cells with AuR@CSA-13, AuR@CSA-44, and AuR@CSA-131 nanosystems was observed. Moreover, the fungicidal mechanism of action of the investigated nanosystems involved the generation of ROS, damage of the fungal cell membrane, and leakage of intracellular contents. Notably, no significant RBCs hemolysis at candidacidal doses of tested nanosystems was detected. Conclusions: The results provide rationale for the development of gold nanoparticles of rod-, peanut-, and star-shaped conjugated with CSA-13, CSA-44, and CSA-131 as effective candidacidal agents.
format	article
author	Karol Skłodowski Sylwia Joanna Chmielewska Joanna Depciuch Piotr Deptuła Ewelina Piktel Tamara Daniluk Magdalena Zakrzewska Michał Czarnowski Mateusz Cieśluk Bonita Durnaś Magdalena Parlińska-Wojtan Paul B. Savage Robert Bucki
author_facet	Karol Skłodowski Sylwia Joanna Chmielewska Joanna Depciuch Piotr Deptuła Ewelina Piktel Tamara Daniluk Magdalena Zakrzewska Michał Czarnowski Mateusz Cieśluk Bonita Durnaś Magdalena Parlińska-Wojtan Paul B. Savage Robert Bucki
author_sort	Karol Skłodowski
title	Ceragenin-Coated Non-Spherical Gold Nanoparticles as Novel Candidacidal Agents
title_short	Ceragenin-Coated Non-Spherical Gold Nanoparticles as Novel Candidacidal Agents
title_full	Ceragenin-Coated Non-Spherical Gold Nanoparticles as Novel Candidacidal Agents
title_fullStr	Ceragenin-Coated Non-Spherical Gold Nanoparticles as Novel Candidacidal Agents
title_full_unstemmed	Ceragenin-Coated Non-Spherical Gold Nanoparticles as Novel Candidacidal Agents
title_sort	ceragenin-coated non-spherical gold nanoparticles as novel candidacidal agents
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/d86f711d7372420690b08ae7e10514a9
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Ceragenin-Coated Non-Spherical Gold Nanoparticles as Novel Candidacidal Agents

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