Vitamin C-Conjugated Nanoparticle Protects Cells from Oxidative Stress at Low Doses but Induces Oxidative Stress and Cell Death at High Doses

High Resolution Image Download MS PowerPoint Slide Although the antioxidant property of vitamin C is well-known for protecting cells from oxidative stress, a recent study shows that it can also generate oxidative stress under a high intracellular concentration and induce cell death. However, poor chemical stability and low biological concentration (micromolar) of vitamin C restrict its function primarily as an antioxidant. Here, we report two different nanoparticle forms of vitamin C with its intact chemical stability, glucose-responsive release from nanoparticle, and efficient cell delivery in micro to millimolar concentrations. Nanoparticles are composed of silica-coated Au nanoparticles or lipophilic polyaspartic acid-based polymer micelles which are conjugated with vitamin C via phenylboronic acid. Surface chemistry of nanoparticles is optimized for an efficient cellular interaction/uptake and for cell delivery of vitamin C. We found that vitamin C protects cells from oxidative stress at micromolar concentrations, but at millimolar concentrations, it induces cell death by generating oxidative stress. In particular, high-dose vitamin C produces H 2 O 2, disrupts the cellular redox balance, and induces cell death. This study highlights the concentration-dependent biological performance of vitamin C and the requirement of a high-dose cell delivery approach for enhanced therapeutic benefit.