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

PLoS One. 2016 Jun 7;11(6):e0157000. doi: 10.1371/journal.pone.0157000. eCollection 2016.

Abstract

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.

MeSH terms

  • Amphotericin B / pharmacology*
  • Antifungal Agents / pharmacology*
  • Cryptococcus neoformans / drug effects*
  • Dose-Response Relationship, Drug
  • Drug Synergism
  • Microbial Sensitivity Tests
  • Nanostructures / chemistry
  • Silver / pharmacology*

Substances

  • Antifungal Agents
  • Silver
  • Amphotericin B

Grant support

This study was supported by the National Key Basic Research Programs of China (2013CB531601), the National Natural Science Foundation of China (81401651, 81471926, and 31170139), the Shanghai Municipal Natural Science Foundation (12JC1411000, 12ZR1454400, and 14495800500), and the Shanghai Key Laboratory of Molecular Medical Mycology (14DZ2272900).