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Ascorbic acid induced HepG2 cells' apoptosis via intracellular reductive stress.
Xiaonan Gao1, Keyan Wei1, Bo Hu1
1College of Chemistry, Chemical Engineering and Materials Science, Collaborative Innovation Center of Functionalized Probes for Chemical Imaging in Universities of Shandong, Key Laboratory of Molecular and Nano Probes, Ministry of Education, Shandong Provincial Key Laboratory of Clean Production of Fine Chemicals, Shandong Normal University, Jinan 250014, P. R. China.
Theranostics
|July 9, 2019
Summary
Researchers developed a novel pH-sensitive nanocarrier that releases ascorbic acid in tumors to induce cancer cell death via reductive stress, sparing healthy tissues. This targeted approach offers a promising, low-toxicity cancer therapy.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Oncology
Background:
- Disrupting the redox balance in tumor cells is crucial for inducing apoptosis and effective cancer treatment.
- Current therapies often cause significant damage to normal tissues, necessitating the development of targeted approaches.
- Hypoxic environments within tumors present a unique target for therapeutic interventions.
Purpose of the Study:
- To design and develop a pH-sensitive, multifunctional nanocarrier for targeted drug delivery.
- To achieve controllable release of ascorbic acid within the tumor microenvironment under hypoxic conditions.
- To induce cancer cell apoptosis through enhanced reductive stress with minimal damage to normal tissues.
Main Methods:
- Fabrication of a core-shell nanostructure using CdTe quantum dots and mesoporous silica.
- Functionalization of the nanocarrier with poly(2-vinylpyridine)-polyethylene glycol-folic acid for targeted delivery.
- Evaluation of pH-dependent, reversible release of ascorbic acid both in vitro and in vivo.
Main Results:
- Ascorbic acid administration led to liver cancer cell death by increasing nicotinamide adenine dinucleotide phosphate (NADPH) levels.
- Normal cells remained unaffected, demonstrating the targeted nature of the treatment.
- The molecular mechanism of ascorbic acid-induced apoptosis was elucidated at the cellular level and confirmed in vivo.
Conclusions:
- The study introduces the novel concept of using reductive stress for cancer treatment, offering a toxicity-free approach.
- The developed nanocarrier system demonstrates significant potential for targeted tumor therapy with reduced side effects.
- This work provides new insights into mild therapeutic strategies and the design of future medicines targeting reductive stress.