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

Abstract

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 HO, 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.

Nanoantioxidants: Recent Trends in Antioxidant Delivery Applications

“…The hydrodynamic size of the resultant Si@AuNP and PAPM are 40-50 nm and 40-80 nm with ∼4-8 wt % and ∼10-13 wt % of vitamin C, respectively. The cellular oxidative stress was evaluated at two different vitamin C concentrations and found that at micromolar concentration it protects the cell, while at millimolar concentration it induces the cell death ( Figure 5b) by generating oxidative stress, particularly by producing H 2 O 2 , which disrupts the cellular redox balance [32].…”

“…(a) Schematic presentation on the synthesis of vitamin C conjugated nanoparticles (Si@AuNP or PAPM) and (b) cellular oxidative stress at micro and millimolar concentration of vitamin C. Adapted with permission from Ref [32]…”

Protective Effect of Nano-Vitamin C on Infertility due to Oxidative Stress Induced by Lead and Arsenic in Male Rats

“…Vitamin C exerted nonenzymatic antioxidant function by destroying free radicals and trapping them in the aqueous phase to protect the biological membrane [21,22]. However, there is a report that high doses of vitamin C have been suggested to cause oxidative stress and cell death [23]. Despite its widespread use as a potent antioxidant in the field of medicine, its use is limited.…”

PEG Grafted Polymethacrylates Bearing Antioxidants as a New Class of Polymer Conjugates for Application in Cosmetology

“…The delivery via conjugates is not limited to drugs, but can be extended to substances such as those useful in medical cosmetology, usually vitamins, such as vitamin E [ 25 , 26 , 27 ], vitamin B12 [ 28 ], folic acid [ 29 ], vitamin C [ 30 ] and vitamin A [ 31 , 32 ]. In most of these studies, they have played the role of a co-delivery substances to assist the carrier in the efficient delivery of anti-cancer drugs indicating a desired cytotoxicity against cancer cells and higher effect of apoptosis than the free drug, diverse drug resistance and reduced side inflammation, or cell protection from oxidative stress at allowed doses.…”