Pharmacologic Vitamin C-Based Cell Therapy via Iron Oxide Nanoparticle-Induced Intracellular Fenton Reaction
Suman Pal, Nikhil R. Jana
Abstract
Although the cytotoxic effect of iron oxide nanoparticle via peroxidase-like activity and associated Fenton reaction is well-known, its effective utilization in cancer therapy is limited because of poor availability of endogenous hydrogen peroxide. Similarly, the cytotoxic effect of vitamin C via hydrogen peroxide generation is well-known but its practical use in cancer therapy is limited due to requirement of high dose (typically above one milimolar) which is not achievable under physiological condition. Here, we show that pharmacologically achievable dose of vitamin C in the range of 0.1–1.0 mM can induce cell death via iron oxide nanoparticle-based intracellular Fenton reaction. Cells are exposed with exogenous vitamin C after labeling with Fe3O4 nanoparticle or directly exposing with vitamin C-conjugated Fe3O4 nanoparticle. Results show that intracellular Fe3O4 nanoparticle can induce cell death by as low as 0.1 mM exogenous vitamin C via Fenton reaction-based intracellular reactive oxygen species (ROS) generation. Following this approach, selective killing of cancer cell has been achieved via functional Fe3O4 nanoparticle-based cell targeting/labeling followed by exogenous vitamin C-based cell therapy. This approach can be extended for other nanoparticles with oxidase/peroxidase-like activity and in designing more effective nanoparticle for vitamin C-based cell therapy.