Synergistic antifungal effect of chitosan-stabilized selenium nanoparticles synthesized by pulsed laser ablation in liquids against Candida albicans biofilms

Humberto H Lara,1 Gregory Guisbiers,2 Jonathan Mendoza,3 Lawrence C Mimun,4 Brandy A Vincent,3 Jose L Lopez-Ribot,1 Kelly L Nash3 1Department of Biology and South Texas Center for Emerging Infectious Diseases, The University of Texas at San Antonio, San Antonio, TX, USA; 2Department of Physics and Astronomy, University of Arkansas at Little Rock, Little Rock, AR, USA; 3Department of Physics and Astronomy, The University of Texas at San Antonio, San Antonio, TX, USA; 4US Army Engineer Research & Development Center, Vicksburg, MS, USA Background: Candida albicans is a major opportunistic fungal pathogen. One of the most important virulence factors that contribute to the pathogenesis of candidiasis is its ability to form biofilms. A key characteristic of Candida biofilms is their resistance to antifungal agents. Due to significant morbidity and mortality rates related to biofilm-associated drug resistance, there is an urgency to develop novel nanotechnology-based approaches preventing biofilm-related infections. Methods: In this study, we report, for the first time, the synthesis of selenium nanoparticles by irradiating selenium pellets by nanosecond pulsed laser ablation in liquid chitosan as a capping agent. Synergy of the fungicidal effect of selenium nanoparticles and chitosan was quantified by the combination index theorem of Chou–Talalay. Results: This drug combination resulted in a potent fungicidal effect against a preformed C. albicans biofilm in a dose–response manner. By advanced electron microscopy techniques, we documented the adhesive and permeabilizing properties of chitosan, therefore allowing selenium nanoparticles to enter as the cell wall of the yeast became disrupted and distorted. Most importantly, we demonstrated a potent quantitative synergistic effect when compounds such as selenium and chitosan are combined. Conclusion: These chitosan-stabilized selenium nanoparticles could be used for ex vivo applications such as sterilizers for surfaces and biomedical devices. Keywords: selenium nanoparticles, laser ablation in liquids, Candida albicans, biofilm, chitosan, synerg