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Vitamin C‑Conjugated Nanoparticle Protects Cells from Oxidative Stress at Low Doses but Induces Oxidative Stress and Cell Death at High Doses
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posted on 2018-03-15, 20:46 authored by Atanu Chakraborty, Nikhil R. JanaAlthough
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.