journal article·2025-09-26Open access

Reactive Oxygen Species-Mediated Oral Cancer Cells Treatment Using Photosensitizer-Combined Carbon Dots via Apoptosis–Ferroptosis Synergistic Therapy

So-Young Park, Mi-Heon Ryu, Wooil Kim, Franklin Garcia-Godoy, Yong Hoon Kwon, Hye-Ock Jang

Applied Sciences· Volume 15· Issue 19

Abstract

In this study, the applicability of carbon dots (CDs) for the treatment of oral cancer cells in vitro was assessed under laser irradiation. For the study, CDs were synthesized using an amino acid via heat treatment and then combined with a photosensitizer. The absorbance and photoluminescence of CDs were measured. The production of reactive oxygen species (ROS) was evaluated using assay agents. The glutathione (GSH) content of the test solutions was evaluated. The viability of normal and cancer cells was evaluated using CDs at different concentrations under laser irradiation. Live/dead cells and intracellular lipid peroxidation (LPO) were observed after treatment. According to the assays, the production of •OH, •O2−, and 1O2 was spectroscopically observed, which was reflected by the change in their peak absorbance. GSH was depleted mostly during light irradiation. Cancer cells were eliminated without leaving visible live cells, whereas normal cells were minimally affected. Intracellular LPO was confirmed in cells by green fluorescence, which was emitted from an oxidized assay dye. Conclusively, the amino acid-based photosensitizer-combined CDs eliminated approximately 70% of the cancer cells in vitro under laser irradiation, with no visible live cells. Based on these assays, ROS production may induce cell death via synergistic apoptosis–ferroptosis therapy.
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Research context

OpenAlex topics: Nanoplatforms for cancer theranostics · Advanced Nanomaterials in Catalysis · Carbon and Quantum Dots Applications

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

Department of Pediatric Dentistry, Dental and Life Science Institute, School of Dentistry, Pusan National University, Yangsan 50612, Republic of Korea

Department of Oral Pathology, Dental and Life Science Institute, School of Dentistry, Pusan National University, Yangsan 50612, Republic of Korea

Department of Dental Materials, Dental and Life Science Institute, School of Dentistry, Pusan National University, Yangsan 50612, Republic of Korea

Department of Bioscience Research, College of Dentistry, University of Tennessee Health Science Center, Memphis, TN 38103, USA

Department of Dental Pharmacology, Dental and Life Science Institute, School of Dentistry, Pusan National University, Yangsan 50612, Republic of Korea

Funding

National Research Foundation of Korea (NRF) grant funded by the Korean government

References (39)

Show source-provided references
1. Effect of tumor microenvironment on pathogenesis of the head and neck squamous cell carcinoma: A systematic review10.1186/s12943-019-0983-5 ↗
2. Head and neck squamous cell carcinoma10.1038/s41572-020-00224-3 ↗
3. Oral squamous cell carcinoma and concomitant primary tumors, what do we know? A review of the literature10.3390/curroncol30040283 ↗
4. A scientometric study of tobacco and alcohol use as risk factors for oral cavity health10.1016/j.jds.2023.05.016 ↗
5. Tobacco and oral squamous cell carcinoma: A review of carcinogenic pathways10.18332/tid/111652 ↗
6. Preventive measures in oral cancer: An overview10.1016/j.biopha.2018.07.114 ↗
7. Niculescu, A.G., and Grumezescu, A.M. (2022). Novel tumor-targeting nanoparticles for cancer treatment—A review. Int. J. Mol. Sci., 23.10.3390/ijms23095253 ↗
8. Nanoparticles for cancer therapy: Current progress and challenges10.1186/s11671-021-03628-6 ↗
9. Recent advances in nanoparticle-based cancer treatment: A review10.1021/acsanm.1c00779 ↗
10. Nano-ROS-generating approaches to cancer dynamic therapy: Lessons from nanoparticles10.1016/j.cej.2022.141225 ↗
11. Recent trends in the application of nanoparticles in cancer therapy: The involvement of oxidative stress10.1016/j.jconrel.2022.05.035 ↗
12. Targeting ROS in cancer: Rationale and strategies10.1038/s41573-024-00979-4 ↗
13. The molecular machinery of regulated cell death10.1038/s41422-019-0164-5 ↗
14. The biochemical pathways of apoptotic, necroptotic, pyroptotic, and ferroptotic cell death10.1016/j.molcel.2023.11.040 ↗
15. The interaction between ferroptosis and lipid metabolism in cancer10.1038/s41392-020-00216-5 ↗
16. Targeting ferroptosis as a vulnerability in cancer10.1038/s41568-022-00459-0 ↗
17. Clinical development and potential of photothermal and photodynamic therapies for cancer10.1038/s41571-020-0410-2 ↗
18. The present and future role of photodynamic therapy in cancer treatment10.1016/S1470-2045(04)01529-3 ↗
19. Csapó, E., and Wojnicki, M. (2023). Carbon Quantum Dots: The Role of Surface Functional Groups and Proposed Mechanisms for Metal Ion Sensing. Inorganics, 11.10.3390/inorganics11060262 ↗
20. Carbon dots in drug delivery and therapeutic applications10.1016/j.addr.2025.115644 ↗
21. Amino acid metabolism in health and disease10.1038/s41392-023-01569-3 ↗
22. Amino Assets: How Amino Acids Support Immunity10.1016/j.cmet.2020.06.010 ↗
23. Recent advances of cancer chemodynamic therapy based on Fenton/Fenton-like chemistry10.1039/D1SC05482A ↗
24. Cao, W., Jin, M., Yang, K., Chen, B., Xiong, M., Li, X., and Cao, G. (2021). Fenton/Fenton-like metal-based nanomaterials combine with oxidase for synergistic tumor therapy. J. Nanobiotechnol., 19.10.1186/s12951-021-01074-1 ↗
25. Eradication of solid tumors by chemodynamic theranostics with H2O2-catalyzed hydroxyl radical burst10.7150/thno.49277 ↗
26. Superoxide dismutase nanozymes: An emerging star for anti-oxidation10.1039/D1TB00720C ↗
27. Artificial Nonenzymatic Antioxidant MXene Nanosheet-Anchored Injectable Hydrogel as a Mild Photothermal-Controlled Oxygen Release Platform for Diabetic Wound Healing10.1021/acsnano.1c10575 ↗
28. A facile method for the synthesis of copper-cysteamine nanoparticles and study of ROS production for cancer treatment10.1039/C9TB01566C ↗
29. Novel albumin-binding photodynamic agent EB-Ppa for targeted fluorescent imaging guided tumour photodynamic therapy10.1039/D2RA07380C ↗
30. Oxidation of 5-thio-2-nitrobenzoic acid, by the biologically-relevant oxidants peroxynitrite anion, hydrogen peroxide and hypochlorous acid10.1016/j.niox.2007.09.087 ↗
31. Enhanced singlet oxygen production over a photocatalytic stable metal organic framework composed of porphyrin and Ag10.1016/j.jcis.2021.05.087 ↗
32. Ferroptosis: Past, present and future10.1038/s41419-020-2298-2 ↗
33. Zhang, W., Liu, Y., Liao, Y., Zhu, C., and Zou, Z. (2024). GPX4, ferroptosis, and diseases. Biomed. Pharmacother., 174.10.1016/j.biopha.2024.116512 ↗
34. Ferroptosis spreads to neighboring cells via plasma membrane contacts10.1038/s41467-025-58175-w ↗
35. Reactive Oxygen Species-Induced Lipid Peroxidation in Apoptosis, Autophagy, and Ferroptosis10.1155/2019/5080843 ↗
36. Targeting ferroptosis as a potential prevention and treatment strategy for aging-related diseases10.1016/j.phrs.2024.107370 ↗
37. ROS-induced lipid peroxidation modulates cell death outcome: Mechanisms behind apoptosis, autophagy, and ferroptosis10.1007/s00204-023-03476-6 ↗
38. Carbon Quantum Dots-Based Nanozyme from Coffee Induces Cancer Cell Ferroptosis to Activate Antitumor Immunity10.1021/acsnano.2c01619 ↗
39. DNA-Free Guanosine-Based Polymer Nanoreactors with Multienzyme Activities for Ferroptosis-Apoptosis Combined Antitumor Therapy10.1021/acsnano.4c11275 ↗