# Improved Photodynamic Inactivation of Resistant Nakaseomyces glabrata Yeasts and Biofilms Mediated by ZnTE-2-PyP4+ Porphyrin Combined with Silver Nanoparticles

## TL;DR

This study shows that combining a porphyrin with silver nanoparticles improves the effectiveness of light-based treatment against drug-resistant fungal infections.

## Contribution

The novel use of ZnTE-2-PyP4+ porphyrin with silver nanoparticles enhances photodynamic inactivation of resistant N. glabrata.

## Key findings

- NE-mediated PDI eradicated resistant N. glabrata cells at 4–5-fold lower porphyrin concentrations.
- NE-PDI reduced biofilm viability by ∼75% and induced significantly higher cell death.
- AgNPs facilitated ZnP-ethyl internalization, likely enhancing PDI efficacy.

## Abstract

Nakaseomyces glabrata is
a high-priority
fungal pathogen due to its incidence and antifungal resistance. Photodynamic
inactivation (PDI) can offer a promising approach against resistant N. glabrata, particularly when the advantageous photophysical
properties of Zn­(II) porphyrins can be enhanced by the plasmonic effect
of metal nanoparticles (NPs). Herein, the association of ZnTE-2-PyP4+ porphyrin (ZnP-ethyl) with AgNPs (stabilized with polyvinylpyrrolidone,
PVP) in PDI against yeasts and biofilms of resistant N. glabrata strains was investigated. AgNPs/ZnP-ethyl
(NE) systems were prepared, and physicochemical characterizations
indicated the interaction and spectral overlap between AgNPs and ZnP-ethyl,
prerequisites for harnessing the plasmonic effect. Moreover, AgNPs
had a minimal effect on ZnP-ethyl fluorescence lifetime. To investigate
the role of AgNPs and strain susceptibility in PDI, yeast interactions
with NE and ZnP-ethyl were assessed by fluorescence microscopy, which
indicated that, in general, AgNPs facilitated the internalization
of ZnP-ethyl by cells. Interestingly, HGV14 yeasts, which were unable
to form biofilm, exhibited the lowest susceptibility to NE-PDI, likely
due to reduced cell interaction relative to the other strains. PDI
using ZnP-ethyl alone at 1.5 μM reduced HGV11 and HGV20 yeasts
by 1 log10, whereas NE-mediated PDI eradicated cells using
4–5-fold lower ZnP-ethyl concentrations. In biofilms, NE-PDI
reduced the viability by ∼75% and induced high cell death to
a much greater extent compared to other irradiated groups. Therefore,
NE boosted the PDI of yeasts and biofilms across all resistant N. glabrata strains, likely driven by plasmonic effect
and enhanced cell interaction promoted by PVP-AgNPs, making NE-PDI
a promising strategy for combating resistant microorganisms.