Comparison of antifungal activities of zinc, copper, cerium oxide, silver, gold, and selenium nanoparticles against clinical isolates of Aspergillus

Document Type : Research Paper


1 Student Research Committee, Mashhad University of Medical Sciences,Mashhad, Iran

2 Blood Transfusion Research Center, High Institute for Research and Education in Transfusion Medicine, Tehran, Iran

3 Department of Basic Medical Sciences, Neyshabur University of Medical Sciences, Neyshabur, Iran

4 Allergy Research Center, Mashhad University of Medical Sciences, Mashhad, Iran

5 Department of Medical Biotechnology and Nanotechnology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

6 Department of Pharmacology, College of medicine, University of Babylon, Babylon, Iraq

7 Department of Physiology, Faculty of Medicine, Kuwait University, Kuwait City, Kuwait


Objective(s): Aspergillus species are found as opportunistic agents to cause a wide variety of clinical manifestations. Regarding the drug resistance emergence against Aspergillus species, new aspects of using nanoparticles (NPs) as antifungal agents are considerable. This study takes a new approach to biosynthesized NPs of zinc oxide, copper oxide, cerium oxide, silver, gold, and selenium influence on the clinical isolates of Aspergillus species.
Materials and Methods: The antifungal activities of six NPs were examined against a total of 12 clinical isolates of Aspergillus species, including A. flavus (n=4), A. welwitschiae (n= 4), and A. fumigatus (n=4) based on the M38-A2 guideline.
Results: According to minimum inhibitory concentration (MIC) values, NPs of ZnO, Ag, Au, and Se showed a significant antifungal effect. CuO-NPs and CeO2-NPs didn’t show an inhibitory effect against Aspergillus isolates. The MIC ranges of ZnO-NPs, Ag-NPs, Au-NPs, and Se-NPs were 128-512, 26-53, 21-85, and 6-26 µg⁄mL for A. fumigatus; and 512->512, 26-53, 85, and 1-13 µg⁄mL for A. welwitschiae, respectively. In addition, the MIC ranges of Ag-NPs and Se-NPs were 26-53 and 106-425 µg⁄mL for A. flavus, respectively. However, A. flavus were not inhibited by NPs of ZnO and Au.
Conclusion: Among the examined NPs, ZnO, Ag, Au, and Se showed a significant effect against Aspergillus isolates except for CuO and CeO2. However, Ag-NPs seemed to be the most effective nanoparticle against the Aspergillus species. Compared to other Aspergillus species, A. flavus was not inhibited by NPs of ZnO and Au.


1.    Zarrinfar H, Saber S, Kordbacheh P, Makimura K, Fata A, Geramishoar M, Mirhendi H: Mycological microscopic and culture examination of 400 bronchoalveolar lavage (BAL) samples. Iran J Public Health. 2012, 41(7):70.
2.    Hosseinikargar N, Basiri R, Asadzadeh M, Najafzadeh MJ, Zarrinfar H: First report of invasive Aspergillus rhinosinusitis in a critically ill COVID‐19 patient affected by acute myeloid leukemia, northeastern Iran. Clin Case Rep. 2021, 9(10):e04889.
3.    Zarrinfar H, Mirhendi H, Fata A, Khodadadi H, Kordbacheh P: Detection of Aspergillus flavus and A. fumigatus in bronchoalveolar lavage specimens of hematopoietic stem cell transplants and hematological malignancies patients by real-time polymerase chain reaction, nested PCR and mycological assays. Jundishapur J Microbiol. 2015, 8(1):e13744.
4.    Hedayati MT, Taghizadeh Armaki M, Yazdani Charati J, Hedayati N, Seyedmousavi S, Denning DW: Burden of fungal infections in Iran. J Infect Dev Ctries 2018, 12(10):910-918.
5.    Osherov N, Kontoyiannis DP: The anti-Aspergillus drug pipeline: is the glass half full or empty? Sabouraudia 2016, 55(1):118-124.
6.    Gerber B, Guggenberger R, Fasler D, Nair G, Manz MG, Stussi G, Schanz U: Reversible skeletal disease and high fluoride serum levels in hematologic patients receiving voriconazole. Blood, Am J Hematol. 2012, 120(12):2390-2394.
7.    Mayr A, Lass-Flörl C: Epidemiology and antifungal resistance in invasive aspergillosis according to primary disease-review of the literature. Eur J Med Res. 2011, 16(4):153-157.
8.    Nabili M, Shokohi T, Moazeni M, Khodavaisy S, Aliyali M, Badiee P, Zarrinfar H, Hagen F, Badali H: High prevalence of clinical and environmental triazole-resistant Aspergillus fumigatus in Iran: is it a challenging issue? J Med Microbiol. 2016, 65(6):468-475.
9.    Omran SM, Taghizadeh-Armaki M, Zarrinfar H, Hedayati MT, Abastabar M, Moqarabzadeh V, Ansari S, Saber S, Hoseinnejad A, Miri A et al: In-vitro antifungal susceptibility testing of lanoconazole and luliconazole against Aspergillus flavus as an important agent of invasive aspergillosis. J Infect Chemother. 2019, 25(2):157-160.
10.    Taghavizadeh Yazdi ME, Darroudi M, Amiri MS, Zarrinfar H, Hosseini HA, Mashreghi M, Mozafarri H, Ghorbani A, Mousavi SH: Antimycobacterial, anticancer, antioxidant and photocatalytic activity of biosynthesized silver nanoparticles using berberis integerrima. Iran J Sci Technol Trans A Sci. 2022, 46(1):1-11.
11.    Kazemi M, Akbari A, Sabouri Z, Soleimanpour S, Zarrinfar H, Khatami M, Darroudi M: Green synthesis of colloidal selenium nanoparticles in starch solutions and investigation of their photocatalytic, antimicrobial, and cytotoxicity effects. Bioprocess Biosyst Eng. 2021, 44(6):1215-1225.
12.    Sakthi Devi R, Girigoswami A, Siddharth M, Girigoswami K: Applications of Gold and Silver Nanoparticles in Theranostics. Appl Biochem Biotechnol. 2022:1-33.
13.    Sun Q, Li J, Le T: Zinc oxide nanoparticle as a novel class of antifungal agents: current advances and future perspectives. J Agric Food Chem. 2018, 66(43):11209-11220.
14.    Bondarenko O, Juganson K, Ivask A, Kasemets K, Mortimer M, Kahru A: Toxicity of Ag, CuO and ZnO nanoparticles to selected environmentally relevant test organisms and mammalian cells in vitro: A critical review. Arch Toxicol. 2013, 87(7):1181-1200.
15.    Stern ST, McNeil SE: Nanotechnology safety concerns revisited. Toxicol Sci. 2008, 101(1):4-21.
16.    Dastjerdi R, Montazer M: A review on the application of inorganic nano-structured materials in the modification of textiles: Focus on anti-microbial properties. Colloids Surf B. 2010, 79(1):5-18.
17.    Cuong HN, Pansambal S, Ghotekar S, Oza R, Hai NTT, Viet NM, Nguyen V-H: New frontiers in the plant extract mediated biosynthesis of copper oxide (CuO) nanoparticles and their potential applications: A review. Environ Res. 2022, 203:111858.
18.    Nabila MI, Kannabiran K: Biosynthesis, characterization and antibacterial activity of copper oxide nanoparticles (CuO NPs) from actinomycetes. Biocatal Agric Biotechnol. 2018, 15:56-62.
19.    Pirmohamed T, Dowding JM, Singh S, Wasserman B, Heckert E, Karakoti AS, King JE, Seal S, Self WT: Nanoceria exhibit redox state-dependent catalase mimetic activity. Chem Commun. 2010, 46(16):2736-2738.
20.    Barker E, Shepherd J, Asencio IO: The use of cerium compounds as antimicrobials for biomedical applications. Molecules. 2022, 27(9):2678.
21.    Ge L, Li Q, Wang M, Ouyang J, Li X, Xing MM: Nanosilver particles in medical applications: synthesis, performance, and toxicity. Int J Nanomedicine. 2014, 9:2399.
22.    Rostami N, Alidadi H, Zarrinfar H, Ketabi D, Tabesh H: Interventional effect of nanosilver paint on fungal load of indoor air in a hospital ward. Can. J Infect Dis Med Microbiol 2021, 2021(8658600):1-6.
23.    Bafghi MH, Darroudi M, Zargar M, Zarrinfar H, Nazari R: Biosynthesis of selenium nanoparticles by Aspergillus flavus and Candida albicans for antifungal applications. Micro Nano Lett. 2021, 16(14):656-669.
24.    Hosseini Bafghi M, Zarrinfar H, Darroudi M, Zargar M, Nazari R: Green synthesis of selenium nanoparticles and evaluate their effect on the expression of ERG3, ERG11 and FKS1 antifungal resistance genes in Candida albicans and Candida glabrata. Lett Appl Microbiol. 2022, 74(5):809-819.
25.    Zanganeh E, Zarrinfar H, Rezaeetalab F, Fata A, Tohidi M, Najafzadeh MJ, Alizadeh M, Seyedmousavi S: Predominance of non-fumigatus Aspergillus species among patients suspected to pulmonary aspergillosis in a tropical and subtropical region of the Middle East. Microb Pathog. 2018, 116:296-300.
26.    Najafzadeh MJ, Dolatabadi S, Zarrinfar H, Houbraken J: Molecular Diversity of Aspergilli in Two Iranian Hospitals. Mycopathologia 2021, 186(4):519-533.
27.    Hedayati MT, Taghizadeh‐Armaki M, Zarrinfar H, Hoseinnejad A, Ansari S, Abastabar M, Er H, Özhak B, Öğünç D, Ilkit M: Discrimination of Aspergillus flavus from Aspergillus oryzae by matrix‐assisted laser desorption/ionisation time‐of‐flight (MALDI‐TOF) mass spectrometry. Mycoses 2019, 62(12):1182-1188.
28.    Alkasir M, Samadi N, Sabouri Z, Mardani Z, Khatami M, Darroudi M: Evaluation cytotoxicity effects of biosynthesized zinc oxide nanoparticles using aqueous Linum Usitatissimum extract and investigation of their photocatalytic activityackn. Inorg Chem Commun. 2020, 119:108066.
29.    Sabouri Z, Sabouri M, Amiri MS, Khatami M, Darroudi M: Plant-based synthesis of cerium oxide nanoparticles using Rheum turkestanicum extract and evaluation of their cytotoxicity and photocatalytic properties. Mater Technol. 2022, 37(8):555-568.
30.    Nasab NK, Sabouri Z, Ghazal S, Darroudi M: Green-based synthesis of mixed-phase silver nanoparticles as an effective photocatalyst and investigation of their antibacterial properties. J Mol Struct. 2020, 1203:127411.
31.    Rasouli E, Basirun WJ, Johan MR, Rezayi M, Darroudi M, Shameli K, Shanavaz Z, Akbarzadeh O, Izadiyan Z: Facile and greener hydrothermal honey‐based synthesis of Fe3O 4/Au core/shell nanoparticles for drug delivery applications. J Cell Biochem. 2019, 120(4):6624-6631.
32.    Velayati M, Hassani H, Sabouri Z, Mostafapour A, Darroudi M: Green-based biosynthesis of Se nanorods in chitosan and assessment of their photocatalytic and cytotoxicity effects. Environ Technol Innov. 2022:102610.
33.    CLSI. Reference Method for Broth Dilution Antifungal Susceptibility Testing of Filamentous Fungi; Approved Standard, 2nd ed. CLSI Document M38–A2, Vol 28, No 16. Wayne, PA: Clinical and Laboratory Standards Institute; 2008.
34.    Zhang H, Hortal M, Dobon A, Jorda‐Beneyto M, Bermudez JM: Selection of Nanomaterial‐Based Active Agents for Packaging Application: Using Life Cycle Assessment (LCA) as a Tool. Packag Technol Sci. 2017, 30(9):575-586.
35.    Yuan X, Setyawati MI, Leong DT, Xie J: Ultrasmall Ag+-rich nanoclusters as highly efficient nanoreservoirs for bacterial killing. Nano Res. 2014, 7(3):301-307.
36.    Hassan A, Howayda M, Mahmoud H: Effect of zinc oxide nanoparticles on the growth of mycotoxigenic mould. SCPT 2013, 1(4):66-74.
37.    Gunalan S, Sivaraj R, Rajendran V: Green synthesized ZnO nanoparticles against bacterial and fungal pathogens. Prog Nat Sci. 2012, 22(6):693-700.
38.    Devipriya D, Roopan SM: Cissus quadrangularis mediated ecofriendly synthesis of copper oxide nanoparticles and its antifungal studies against Aspergillus niger, Aspergillus flavus. Mater Sci Eng. C2017, 80:38-44.
39.    Velsankar K, RM AK, Preethi R, Muthulakshmi V, Sudhahar S: Green synthesis of CuO nanoparticles via Allium sativum extract and its characterizations on antimicrobial, antioxidant, antilarvicidal activities. J Environ Chem. Eng.2020, 8(5):104123.
40.    Mohamed HEA, Afridi S, Khalil AT, Ali M, Zohra T, Akhtar R, Ikram A, Shinwari ZK, Maaza M: Promising antiviral, antimicrobial and therapeutic properties of green nanoceria. Nanomedicine 2020, 15(05):467-488.
41.    Maqbool Q, Nazar M, Naz S, Hussain T, Jabeen N, Kausar R, Anwaar S, Abbas F, Jan T: Antimicrobial potential of green synthesized CeO2 nanoparticles from Olea europaea leaf extract. Int J Nanomed. 2016, 11:5015.
42.    Hosseini Bafghi M, Safdari H, Nazari R, Darroudi M, Sabouri Z, Zargar M, Zarrinfar H: Evaluation and comparison of the effects of biosynthesized selenium and silver nanoparticles using plant extracts with antifungal drugs on the growth of Aspergillus and Candida species. Rend Lincei Sci Fis.2021, 32(4):791-803.
43.    Giljohann DA, Seferos DS, Daniel WL, Massich MD, Patel PC, Mirkin CA: Gold nanoparticles for biology and medicine. Angew Chem Int Ed Engl. 2010;49(19):3280-3294.
44.    Khan S, Alam F, Azam A, Khan AU: Gold nanoparticles enhance methylene blue–induced photodynamic therapy: A novel therapeutic approach to inhibit Candida albicans biofilm. Int J Nanomedicine. 2012:3245-3257.
45.    Jebali A, Hajjar FHE, Hekmatimoghaddam S, Kazemi B, Jesus M, Rashidi M: Triangular gold nanoparticles conjugated with peptide ligands: a new class of inhibitor for Candida albicans secreted aspartyl proteinase. Biochem. Pharmacol. 2014, 90(4):349-355.
46.    Kheradmand E, Rafii F, Yazdi MH, Sepahi AA, Shahverdi AR, Oveisi MR: The antimicrobial effects of selenium nanoparticle-enriched probiotics and their fermented broth against Candida albicans. DARU J Pharm Sci. 2014, 22:1-6.
47.    Shakibaie M, Mohazab NS, Mousavi SAA: Antifungal activity of selenium nanoparticles synthesized by Bacillus species Msh-1 against Aspergillus fumigatus and Candida albicans. Jundishapur J Microbiol. 2015, 8(9):e26381.