Pd@Ag Nanosheets in Combination with Amphotericin B Exert a Potent Anti-Cryptococcal Fungicidal Effect

• Published in: PloS one 2016-06, Vol.11 (6), p.e0157000
• Main Authors: Zhang, Chao, Chen, Mei, Wang, Guizhen, Fang, Wei, Ye, Chen, Hu, Hanhua, Fa, Zhenzong, Yi, Jiu, Liao, Wan-Qing
• Format: Article
• Language: English
• Subjects: Amphotericin B; Amphotericin B - pharmacology; Antifungal activity; Antifungal agents; Antifungal Agents - pharmacology; Antimicrobial agents; Bacteria; Biology and Life Sciences; Candida; Chemistry; Complications and side effects; Core-shell structure; Cryptococcosis; Cryptococcus; Cryptococcus neoformans; Cryptococcus neoformans - drug effects; Dermatology; Dosage and administration; Dose-Response Relationship, Drug; Drug resistance; Drug Synergism; Energy metabolism; Engineering and Technology; Erythrocytes; Fluconazole; Fungal infections; Fungi; Fungicidal activity; Fungicides; Laboratories; Low concentrations; Medicine and Health Sciences; Meningitis; Metabolism; Microbial Sensitivity Tests; Microorganisms; Molecular chains; Nanomaterials; Nanoparticles; Nanosheets; Nanostructure; Nanostructures - chemistry; Nanotechnology; Palladium; Physiological aspects; Properties; Protein biosynthesis; Protein synthesis; Protein turnover; Proteins; Saccharomyces cerevisiae; Silver; Silver - pharmacology; Therapeutic applications; Toxicity
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0157000

Silver nanoparticles have received considerable interest as new "nanoantibiotics" with the potential to kill drug-resistant microorganisms. Recently, a class of new core-shell nanostructures, Pd@Ag nanosheets (Pd@Ag NSs), were created using deposition techniques and demonstrated excellent inhibitory effects on various bacteria in vitro. In this study, we evaluated the antifungal activity of Pd@Ag NSs against common invasive fungal pathogens. Among these organisms, Cryptococcus neoformans complex species was most susceptible to Pd@Ag NSs, which exhibited potent antifungal activity against various molecular types or sources of cryptococcal strains including fluconazole-resistant isolates. The anticryptococcal activity of Pd@Ag NSs was significantly greater than fluconazole and similar to that of amphotericin B (AmB). At relatively high concentrations, Pd@Ag NSs exhibited fungicidal activity against Cryptococcus spp., which can likely be attributed to the disruption of cell integrity, intracellular protein synthesis, and energy metabolism. Intriguingly, Pd@Ag NSs also exhibited strong synergistic anti-cryptococcal fungicidal effects at low concentrations in combination with AmB but exhibited much better safety in erythrocytes than AmB, even at the minimal fungicidal concentration. Therefore, Pd@Ag NSs may be a promising adjunctive agent for treating cryptococcosis, and further investigation for clinical applications is required.