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

• Published in: ACS applied materials & interfaces 2017-12, Vol.9 (48), p.41807-41817
• Main Authors: Chakraborty, Atanu, Jana, Nikhil R
• Format: Article
• Language: English
• Subjects: Ascorbic Acid; Cell Death; Hydrogen Peroxide; Nanoparticles; Oxidative Stress; Reactive Oxygen Species
• ISSN: 1944-8244; 1944-8252
• DOI: 10.1021/acsami.7b16055

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 H2O2, 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.