In vitro studies on oxidative stress-independent, Ag nanoparticles-induced cell toxicity of Candida albicans, an opportunistic pathogen

Venkatraman Srinivasan Radhakrishnan,1 Surya Prakash Dwivedi,2 Mohammed Haris Siddiqui,3 Tulika Prasad1 1Advanced Instrumentation Research Facility (AIRF), Jawaharlal Nehru University, New Delhi, 2School of Biotechnology, IFTM University, Moradabad, 3Department of Bioengineering, Integral University, Lucknow, Uttar Pradesh, India Abstract: Silver nanoparticles (AgNps) have attracted maximal attention among all metal nanoparticles, and the study of their biological properties has gained impetus for further medical adoption. This study evaluated the cellular and molecular mechanisms associated with the action of AgNps against an opportunistic pathogen, Candida albicans. Spherical, stable AgNp (average size 21.6 nm) prepared by a chemical reduction method showed minimum inhibitory concentration (required to inhibit the growth of 90% of organisms) at 40 µg/mL. AgNps have been reported to induce oxidative stress-mediated programmed cell death through the accumulation of intracellular reactive oxygen species (ROS). However, this study demonstrated that intracellular levels of AgNp-induced ROS could be reversed by using antioxidant ascorbic acid, but the sensitivity of AgNp-treated Candida cells could not be completely reversed. Moreover, in addition to the generation of ROS, the AgNps were found to affect other cellular targets resulting in altered membrane fluidity, membrane microenvironment, ergosterol content, cellular morphology, and ultrastructure. Thus, the generation of ROS does not seem to be the sole major cause of AgNp-mediated cell toxicity in Candida. Rather, the multitargeted action of AgNps, generation of ROS, alterations in ergosterol content, and membrane fluidity together seem to have potentiated anti-Candida action. Thus, this “nano-based drug therapy” is likely to favor broad-spectrum activity, multiple cellular targets, and minimum host toxicity. AgNps, therefore, appear to have the potential to address the challenges in multidrug resistance and fungal therapeutics. Keywords: antifungal, nanomedicine, ROS, drug resistanc