A Novel Strategy Based on Zn(II) Porphyrins and Silver Nanoparticles to Photoinactivate Candida albicans

Int J Nanomedicine. 2023 Jun 7:18:3007-3020. doi: 10.2147/IJN.S404422. eCollection 2023.

Abstract

Background: Photodynamic inactivation (PDI) is an attractive alternative to treat Candida albicans infections, especially considering the spread of resistant strains. The combination of the photophysical advantages of Zn(II) porphyrins (ZnPs) and the plasmonic effect of silver nanoparticles (AgNPs) has the potential to further improve PDI. Here, we propose the novel association of polyvinylpyrrolidone (PVP) coated AgNPs with the cationic ZnPs Zn(II) meso-tetrakis(N-ethylpyridinium-2-yl)porphyrin or Zn(II) meso-tetrakis(N-n-hexylpyridinium-2-yl)porphyrin to photoinactivate C. albicans.

Methods: AgNPs stabilized with PVP were chosen to allow for (i) overlap between the NP extinction and absorption spectra of ZnPs and (ii) favor AgNPs-ZnPs interaction; prerequisites for exploring the plasmonic effect. Optical and zeta potential (ζ) characterizations were performed, and reactive oxygen species (ROS) generation was also evaluated. Yeasts were incubated with individual ZnPs or their respective AgNPs-ZnPs systems, at various ZnP concentrations and two proportions of AgNPs, then irradiated with a blue LED. Interactions between yeasts and the systems (ZnP alone or AgNPs-ZnPs) were evaluated by fluorescence microscopy.

Results: Subtle spectroscopic changes were observed for ZnPs after association with AgNPs, and the ζ analyses confirmed AgNPs-ZnPs interaction. PDI using ZnP-hexyl (0.8 µM) and ZnP-ethyl (5.0 µM) promoted a 3 and 2 log10 reduction of yeasts, respectively. On the other hand, AgNPs-ZnP-hexyl (0.2 µM) and AgNPs-ZnP-ethyl (0.6 µM) systems led to complete fungal eradication under the same PDI parameters and lower porphyrin concentrations. Increased ROS levels and enhanced interaction of yeasts with AgNPs-ZnPs were observed, when compared with ZnPs alone.

Conclusion: We applied a facile synthesis of AgNPs which boosted ZnP efficiency. We hypothesize that the plasmonic effect combined with the greater interaction between cells and AgNPs-ZnPs systems resulted in an efficient and improved fungal inactivation. This study provides insight into the application of AgNPs in PDI and helps diversify our antifungal arsenal, encouraging further developments toward inactivation of resistant Candida spp.

Keywords: fungi; photodynamic inactivation; photosensitizer; plasmon.

MeSH terms

  • Candida albicans
  • Metal Nanoparticles*
  • Porphyrins*
  • Povidone
  • Reactive Oxygen Species
  • Silver / pharmacology
  • Zinc / pharmacology

Substances

  • pyrithione zinc
  • Silver
  • Reactive Oxygen Species
  • Porphyrins
  • Povidone
  • Zinc

Grants and funding

This research was funded by Wellcome Trust, grant 219677_Z_19_Z; Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq, 406450/2021-8, 314241/2021-3, 424159/2018-0); Fundação de Amparo à Ciência e Tecnologia do Estado de Pernambuco (FACEPE, APQ-0573-2.09/18); and Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP, n° 2018/20226-7). This study is also associated with the Instituto Nacional de Ciência e Tecnologia em Fotônica (INCT-INFo). The APC was funded by Wellcome Trust. GP acknowledges financial support to CESAM by FCT/MCTES (UIDP/50017/2020+UIDB/50017/2020+LA/P/0094/2020), through national funds. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.