Chitosan nanoparticles' functionality as redox active drugs through cytotoxicity, radical scavenging and cellular behaviour

Targeting the oxidative stress response has recently emerged as a promising strategy for the development of therapeutic drugs for a broad spectrum of diseases. Supporting this strategy, we have reported that chitosan nanoparticles synthesized with a controlled size had selective cytotoxicity in leukemia cells through the mechanism related to reactive oxygen species (ROS) generation. Herein, we found that the cellular uptake of chitosan nanoparticles was enhanced in a time dependent manner and inhibited the cellular proliferation of leukemia cells in a dose dependent manner with elevation of the reactive oxygen species (ROS) showing a stronger effect on apoptosis, associated with the upregulation of caspase activity and the depletion of reduced glutathione. Propidium iodide and calcein staining demonstrated the central role of the chitosan nanoparticles in triggering elevated ROS, inducing cell death and intracellular oxidative activity. The enhanced free radical scavenging activity of the chitosan nanoparticles further iterates its antioxidant activity. In vitro quantitative phase imaging studies at the single cell level further demonstrated the inhibition of cellular proliferation with significant changes in cellular behavior and this supported our hypothesis. Hemocompatibility tests demonstrated that chitosan nanoparticles could be used safely for in vivo applications. Our findings suggest that chitosan nanoparticles may be a promising redox active candidate for therapeutic applications.