Metal Nanoparticles to Combat Candida albicans Infections: An Update Original paper

What was reviewed?

This article is a comprehensive review focusing on the use of metal nanoparticles as novel antifungal agents against Candida albicans infections. It specifically examines the antifungal activity, mechanisms of action, synthesis methods, cytotoxicity concerns, and drug delivery potential of silver, gold, iron, and other metal nanoparticles. The review also discusses the challenges posed by traditional antifungal therapies and the promise of nanoparticle-based strategies to overcome drug resistance and biofilm-related treatment failures.

Who was reviewed?

The review synthesizes findings from multiple in vitro and in vivo studies involving Candida albicans cells in planktonic and biofilm states, experimental animal models of candidiasis, and mammalian cell lines used to evaluate nanoparticle cytotoxicity. It integrates results from research using a variety of metal nanoparticles, primarily silver (AgNPs), gold (AuNPs), and iron oxide nanoparticles (IONPs), and their functionalized or bimetallic forms. The studies encompass fungal strains that are susceptible and resistant to conventional antifungal drugs, as well as biofilms formed on mucosal surfaces and medical devices.

Most important findings

The review highlights that metal nanoparticles exhibit potent antifungal activity against Candida albicans through multi-target mechanisms, including metal ion release, induction of oxidative and nitrosative stress, disruption of the fungal cell wall and membrane, inhibition of enzymatic activities, interference with gene expression related to virulence and resistance, and mitochondrial and DNA damage. Silver nanoparticles, particularly when combined with fluconazole, demonstrated synergistic antifungal effects by reducing biofilm formation, decreasing ergosterol levels, and downregulating efflux pump proteins responsible for drug resistance. Gold nanoparticles, especially those functionalized with polymers like chitosan or polyethylene glycol, showed enhanced drug delivery capabilities with lower toxicity and effective inhibition of fungal growth and biofilm formation. Iron oxide nanoparticles proved effective as drug carriers, improving the potency of drugs like amphotericin B and miconazole, and inducing fungal cell damage through ROS generation.

Beyond these, other metal nanoparticles such as zinc oxide, titanium dioxide, copper oxides, and zirconium dioxide also showed antifungal and antibiofilm properties. Bimetallic nanoparticles, combining metals like silver and iron or silver and nickel, provided synergistic antifungal effects, reduced fungal virulence factors, and overcame drug resistance. Importantly, the synthesis methods, especially green synthesis using natural extracts, contributed to enhanced biocompatibility and reduced cytotoxicity. However, cytotoxicity to mammalian cells remains a significant consideration, with ongoing efforts to optimize nanoparticle properties for safety. The review also calls for further exploration of nanoparticle effects on polymicrobial biofilms involving C. albicans and bacterial species, and the role of fungal siderophore transporters in nanoparticle uptake.

Greatest implications of this review

This review underscores the potential of metal nanoparticles as a promising alternative or adjunct to conventional antifungal therapies, particularly for drug-resistant Candida albicans infections and biofilm-related candidiasis. The multi-target antifungal mechanisms of metal nanoparticles may minimize the emergence of resistance, a critical challenge in current treatment paradigms. Their ability to act as drug delivery vehicles could reduce effective drug doses and associated toxicity. The integration of green synthesis methods enhances their environmental and biological safety profiles, making clinical translation more feasible. Nevertheless, the review highlights the urgent need for further in vivo studies, clinical trials, and regulatory guidance to assess long-term safety, biodistribution, and potential adverse effects. Understanding nanoparticle interactions in polymicrobial biofilms and their uptake pathways can refine future antifungal strategies. Overall, metal nanoparticles represent a cutting-edge approach that could revolutionize antifungal therapeutics and improve outcomes for patients suffering from C. albicans infections.