A paper recently published in the journal ACS Applied Nano Materials reviewed the potential of therapeutic applications based on the pro-oxidant properties of vitamin C through nanotechnology.
Study: Enhanced Therapeutic Applications of Vitamin C via Nanotechnology-Based Pro-Oxidant Properties: A Review. Image Credit: Gargonia/Shutterstock.com
Significance of Vitamin C as a Nutrient
Vitamin C is one of the essential nutrients for the human body as it is involved in an extensive range of biochemical activities such as the prevention of oxidative stress and tissue repair. The nutrient also plays a crucial role in hormonal and pathogen responses and the cellular growth of plants.
Vitamin C is commonly found in different food and food supplements. Although most animals can independently produce vitamin C, humans have to depend on dietary supplements as their bodies cannot produce this nutrient.
The biological function of vitamin C is directly linked to its chemical properties For instance, the antioxidant property is utilized for oxidative stress management in biology, while the pro-oxidant property is used for cancer therapy.
Vitamin C easily oxidizes in the presence of catalytic metals and dissolved oxygen as it is a weak reducing agent, which leads to the generation of hydrogen peroxide and other reactive oxygen species (ROS). ROS-induced oxidative stress is often associated with several diseases.
Additionally, vitamin C also plays a critical role in controlling diseases caused by oxidative stress by scavenging the additional ROS in the biological system, which shows the antioxidant property of the nutrient. Although the antioxidant property of vitamin C was well-established, the pro-oxidant property was discovered more recently. However, easier oxidation of vitamin C is responsible for poor chemical stability, which leads to lower non-toxicity and bioavailability even at higher doses of vitamin C and restricts its use as a pro-oxidant/antioxidant in biomedical applications.
Pro-oxidant Property and antioxidant Property of Vitamin C
The antioxidant property of vitamin C is attributed to the generation of a stable vitamin C radical through the donation of a single atom to ROS as the process absorbs and deactivates ROS. Vitamin C acts as an antioxidant when its concentration is less than 0.1 millimolar and the pH is neutral.
The pro-oxidant property of vitamin C can be observed in two conditions. The first condition is the vitamin C auto-oxidation when the vitamin C concentration is more than four millimolar and the pH value is over seven. In these conditions, the vitamin C dianion reacts with the molecular oxygen to produce a superoxide radical and vitamin C radical. The second condition is vitamin C oxidation by metal ion catalysts followed by the Fenton reaction.
Vitamin C Delivery Approaches to Achieve Improved Therapeutic Outcomes
To stabilize vitamin C and achieve enhanced therapeutic performance with low vitamin C doses, three delivery approaches can be followed. The first approach involves the use of nanoscale carriers such as chitosan for intracellular delivery of vitamin C. These nanocarriers encapsulate the molecular vitamin C within the particle core to prevent the degradation of the nutrient from the external bioenvironment.
The second approach includes the use of transition metal-based nanoparticles for the generation of catalytic ROS from vitamin C for effective therapy, while the third approach involves the use the nanotechnology with vitamin C therapy for precise targeting of tumor/cell.
Among all these approaches, the nanocarrier-based approach is more suitable compared to other approaches in improving the in vivo stability of drugs with enhanced pharmacokinetic activity and targeting a property. The transformation of the molecular vitamin C to nano-vitamin C is the most effective approach to realize improved therapeutic performance.
Nano-vitamin C displays better chemical stability in blood vessels and under complex physiological conditions and ensures more intracellular availability of vitamin C.
Therapeutic Applications of Nano-Vitamin C with Enhanced Pro-Oxidant Property
Nano-vitamin C Therapy with Enhanced ROS Generation
Vitamin C in nanoparticle forms displays enhanced cell delivery efficiency and improved chemical stability against oxidation. The pro-oxidant property can be realized in low vitamin C dosage in nanoscale delivery systems compared to the high vitamin C dosage required in traditional delivery systems. For instance, the palmitoyl ascorbate encapsulated liposome nanocarrier showed an anticancer effect in animal and cell models at less than four millimolar concentrations of vitamin C.
Vitamin C-Based Ferroptosis Therapy
The pro-oxidant property of vitamin C can also be realized at a low dosage using a catalytic metal that can induce vitamin C oxidation and ROS generation through the Fenton reaction. Typically, iron is utilized as a catalytic metal in this therapeutic application composed of catalytic metal and nano-vitamin C, and the approach is referred to as Ferroptosis therapy. The pro-oxidant property of vitamin C can be realized at less than one millimolar concentration through this approach.
Vitamin C-Based Therapy Based on Other Catalytic Metal-Based Nanoparticles
Apart from iron, several other catalytic metals, such as metal nanoparticles and redox couples of coppers I/ copper II, are also used for ROS generation based on the Fenton reaction. For instance, a copper−peptide complex that facilitates a vitamin C-induced Fenton reaction at mitochondria has considerably increased cancer cell killing efficiency of vitamin C at 200 micromolar concentration through the generation of hydroxyl radical.
To summarize, the pro-oxidant property of vitamin C holds significant potential in several therapeutic applications, specifically in targeted tumor and cell therapy applications. However, more research is required to effectively utilize its full potential in the molecular mechanism of cell therapy and advanced in vivo delivery approaches.
Jana, N. R., Pal, S. (2022) Enhanced Therapeutic Applications of Vitamin C via Nanotechnology-Based Pro-Oxidant Properties: A Review. ACS Applied Nano Materials. https://pubs.acs.org/doi/10.1021/acsanm.1c03000.