Characterization of Key Bio–Nano Interactions between Organosilica Nanoparticles and Candida albicans

Abstract

Nanoparticle−cell interactions between silica nanomaterials and mammalian cells have been investigated extensively in the context of drug delivery, diagnostics, and imaging. While there are also opportunities for applications in infectious disease, the interactions of silica nanoparticles with pathogenic microbes are relatively underexplored. To bridge this knowledge gap, here, we investigate the effects of organosilica nanoparticles of different sizes, concentrations, and surface coatings on surface association and viability of the major human fungal pathogen Candida albicans. We show that uncoated and PEGylated organosilica nanoparticles associate with C. albicans in a size and concentration-dependent manner, but on their own, do not elicit antifungal activity. The particles are also shown to associate with human white blood cells, in a similar trend as observed with C. albicans, and remain noncytotoxic toward neutrophils. Smaller particles are shown to have low association with C. albicans in comparison to other sized particles and their association with blood cells was also observed to be minimal. We further demonstrate that by chemically immobilizing the clinically important echinocandin class antifungal drug, caspofungin, to PEGylated nanoparticles, the cell−material interaction changes from benign to antifungal, inhibiting C. albicans growth when provided in high local concentration on a surface. Our study provides the foundation for defining how organosilica particles could be tailored for clinical applications against C. albicans. Possible future developments include designing biomaterials that could detect, prevent, or treat bloodstream C. albicans infections, which at present have very high patient mortality.

Dynamic Solid-State Ultrasound Contrast Agent for Monitoring pH Fluctuations In Vivo

“…At this point, before live animal imaging, we also evaluated the cytotoxicity of the sUNs on NIH/3T3 cells using an Alamar Blue assay. The sUN particles showed negligible toxicity on the cells in comparison to the control (Figure S5), consistent with recent studies from our groups and others on the biocompatibility of organosilica materials. − sUNs and cores were initially injected into the flank skin of mice in the PBS pH 7 buffer, followed by an injection of low-pH PBS to transiently reduce the local tissue pH. Images were collected every 5 min over 15 min, and we observed a significant increase in contrast for the sUNs in comparison to a constant signal for the silica cores (Figure ).…”

Enhanced Emission of Zinc Nitride Colloidal Nanoparticles with Organic Dyes for Optical Sensors and Imaging Application

“…Functionalization with inorganic nanomaterials enables imaging with reduced toxicity and enhances the brightness with low background noises. Compared to widely used organic dyes, semiconductor quantum dots and nanoparticles are attractive in imaging due to optical property, stability, brightness, lesser photobleaching, and high detection limit. − The inorganic nanoparticles include luminescent silica nanoparticles, , carbon dots, nanotubes, nanoclusters, nanodiamonds, and metal oxides . Colloidal quantum dots such as CdS, CdSe, CdTe, PbS, PbSe, and HgTe have potential cytotoxicity during in vitro and in vivo despite efficient photo emission .…”

Candida albicans Can Survive Antifungal Surface Coatings on Surfaces with Microcone Topography

“…The antifungal nature of the surface coating is further characterized by studying the viability of the fungal cells growing in the supernatant above the samples, away from direct surface contact. From the literature, the activity of surface-attached caspofungin is thought to occur via inhibition of the 1,3-β glucan synthase enzyme in the Candida albicans cell wall. , Figure b shows the growth of Candida albicans in supernatants. As shown in Figure b, the growth of Candida albicans takes place in the supernatant of the growth media, regardless of the nature of the surface chemistries of the sample materials, confirming that suppression of fungal growth on caspofungin coated surfaces occurs via a mode of action of caspofungin that is contact dependent and leads to cell death only on the surface and not through diffusion of caspofungin into fungal cells in solution, in accord with earlier results …”