A Carbon-Based Nanomaterial with Dichotomous Effects: Antineoplastic on Oral Cancer Cells and Osteoinductive/Chondroinductive on Dental Pulp Stem Cells
Source abstract
Abstract
Background: Oral cancer is an aggressive malignancy with modest survival rates. It also causes disfigurement following surgical removal of the tumor, thus highlighting the need for new cancer treatment and tissue repair modalities. Carbon-based nanomaterials have emerged as promising tools in both anticancer and regenerative therapies. Objectives: We aimed to synthesize a new carbon-based nanomaterial (CBN) and test its antineoplastic effects, as well as its potential regenerative capacity. Materials and Methods: A carbon nanomaterial, obtained by ball milling graphite flakes, was functionalized with polyvinylpyrrolidone (CBN/PVP). Its physicochemical properties were explored with X-ray diffraction (XRD), attenuated total reflection–Fourier transform infrared spectroscopy (ATR-FTIR), micro-Raman spectroscopy, fluorescent and scanning electron microscopy, and wettability analysis. For the antineoplastic effects investigation, oral cancer cells were treated with CBN/PVP and examined with MTT and migration assays, as well as cell-cycle and ROS production analyses. Gene expression was determined by qPCR. To examine the pro-regenerative capacity of CBN/PVP, dental pulp stem cell cultures (DPSCs) were treated with the nanomaterial and subjected to osteo- and chondro-induction. Results: Lower concentrations of CBN/PVP (50, 100 μg/mL) applied on cancer cells exerted remarkable cytotoxic effects, induced G1 cell-cycle arrest, and reduced cancer cell invasion potential by different mechanisms, including downregulation of the PI3K/AKT/mTOR pathway. In contrast, the addition of 50 µg/mL of CBN/PVP to DPSCs stimulated their survival and proliferation. CBN/PVP significantly enhanced both the osteogenic (p < 0.05) and chondrogenic (p < 0.01) induction of DPSCs. Conclusions: The novel carbon-based nanomaterial displays unique characteristics, making it suitable in anticancer and regenerative therapies concomitantly.
Source: crossref · Quality: baseline
Research context
OpenAlex topics: Graphene and Nanomaterials Applications · Cancer Research and Treatment · Carbon and Quantum Dots Applications
SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.
Affiliations
School of Dental Medicine, University of Belgrade, 11000 Belgrade, Serbia
Vinča Institute of Nuclear Sciences—National Institute of the Republic of Serbia, University of Belgrade, P.O. Box 522, 11001 Belgrade, Serbia
SGL Carbon, 86405 Meitingen, Bavaria, Germany
Innovative Company ALBOS DOO, 11000 Belgrade, Serbia
Funding
Science Fund of the Republic of Serbia
References (53)
Show source-provided references
1. Cancer Stem Cells of Head and Neck Squamous Cell Carcinoma; Distance towards Clinical Application: A Systematic Review of Literature
2. Radiotherapy Targeting Cancer Stem Cells “Awakens” Them to Induce Tumour Relapse and Metastasis in Oral Cancer10.1038/s41368-020-00087-0 ↗
3. Global Cancer Statistics 2018: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries10.3322/caac.21492 ↗
4. Imbesi Bellantoni, M., Picciolo, G., Pirrotta, I., Irrera, N., Vaccaro, M., Vaccaro, F., Squadrito, F., and Pallio, G. (2023). Oral Cavity Squamous Cell Carcinoma: An Update of the Pharmacological Treatment. Biomedicines, 11.10.3390/biomedicines11041112 ↗
5. The Pathology of Oral Cancer
6. Efficient miRNA Inhibitor Delivery with Graphene Oxide-Polyethylenimine to Inhibit Oral Squamous Cell Carcinoma10.2147/IJN.S220057 ↗
7. Sharma, H., and Mondal, S. (2020). Functionalized Graphene Oxide for Chemotherapeutic Drug Delivery and Cancer Treatment: A Promising Material in Nanomedicine. Int. J. Mol. Sci., 21.10.3390/ijms21176280 ↗
8. The Immunotoxicity of Graphene Oxides and the Effect of PVP-Coating10.1016/j.biomaterials.2013.03.024 ↗
9. Zhang, J., Cao, H.-Y., Wang, J.-Q., Wu, G.-D., and Wang, L. (2021). Graphene Oxide and Reduced Graphene Oxide Exhibit Cardiotoxicity Through the Regulation of Lipid Peroxidation, Oxidative Stress, and Mitochondrial Dysfunction. Front. Cell Dev. Biol., 9.10.3389/fcell.2021.616888 ↗
10. Cellular Behaviours of Bone Marrow-Derived Mesenchymal Stem Cells towards Pristine Graphene Oxide Nanosheets10.1111/cpr.12367 ↗
11. Li, R., Wang, Y., Du, J., Wang, X., Duan, A., Gao, R., Liu, J., and Li, B. (2021). Graphene Oxide Loaded with Tumor-Targeted Peptide and Anti-Cancer Drugs for Cancer Target Therapy. Sci. Rep., 11.10.1038/s41598-021-81218-3 ↗
12. PI3K/AKT Signaling Pathway Mediated Autophagy in Oral Carcinoma—A Comprehensive Review10.7150/ijms.94566 ↗
13. Xu, J., Dong, X., Huang, D.C.S., Xu, P., Zhao, Q., and Chen, B. (2023). Current Advances and Future Strategies for BCL-2 Inhibitors: Potent Weapons against Cancers. Cancers, 15.10.3390/cancers15204957 ↗
14. Shah, P.A., Huang, C., Li, Q., Kazi, S.A., Byers, L.A., Wang, J., Johnson, F.M., and Frederick, M.J. (2020). NOTCH1 Signaling in Head and Neck Squamous Cell Carcinoma. Cells, 9.10.3390/cells9122677 ↗
15. Farjaminejad, S., Farjaminejad, R., and Garcia-Godoy, F. (2024). Nanoparticles in Bone Regeneration: A Narrative Review of Current Advances and Future Directions in Tissue Engineering. J. Funct. Biomater., 15.10.3390/jfb15090241 ↗
16. Vukovic, M., Lazarevic, M., Mitic, D., Jaksic Karisik, M., Ilic, B., Andric, M., Jevtic, B., Roganovic, J., and Milasin, J. (2022). Acetylsalicylic-Acid (ASA) Regulation of Osteo/Odontogenic Differentiation and Proliferation of Human Dental Pulp Stem Cells (DPSCs) in Vitro. Arch. Oral Biol., 144.10.1016/j.archoralbio.2022.105564 ↗
17. Herendija, E., Jakšić Karišik, M., Milašin, J., Lazarević, M., and Ignjatović, N. (2024). Anti-Cancer Activities of Nano Amorphous Calcium Phosphates toward Premalignant and Oral Cancer Cells. Biomedicines, 12.10.3390/biomedicines12071499 ↗
18. NOX Enzymes in the Central Nervous System: From Signaling to Disease10.1089/ars.2009.2578 ↗
19. Analysis of Relative Gene Expression Data Using Real-Time Quantitative PCR and the 2(-Delta Delta C(T)) Method10.1006/meth.2001.1262 ↗
20. Comparison of the Characteristic Properties of Reduced Graphene Oxides Synthesized from Natural Graphites with Different Graphitization Degrees10.1039/C7RA10809E ↗
21. Liquid Phase Production of Graphene by Exfoliation of Graphite in Surfactant/Water Solutions10.1021/ja807449u ↗
22. Effect of Airborne Contaminants on the Wettability of Supported Graphene and Graphite10.1038/nmat3709 ↗
23. (2025, March 03). Flower-Like Morphology of Naphthalene Diimides Containing tetra-L- and D-Alanine—Shaikh—2020—ChemistrySelect—Wiley Online Library. Available online: https://chemistry-europe.onlinelibrary.wiley.com/doi/abs/10.1002/slct.202003108.
24. Characterization of the Intrinsic Water Wettability of Graphite Using Contact Angle Measurements: Effect of Defects on Static and Dynamic Contact Angles10.1021/acs.langmuir.6b04193 ↗
25. Pierfelice, T.V., Lazarevic, M., Mitic, D., Nikolic, N., Radunovic, M., Iezzi, G., Piattelli, A., and Milasin, J. (2023). Red Light and 5% Aminolaevulinic Acid (5%) Inhibit Proliferation and Migration of Dysplastic Oral Keratinocytes via ROS Production: An In Vitro Study. Gels, 9.10.3390/gels9080604 ↗
26. Gurunathan, S., Kang, M.-H., Qasim, M., and Kim, J.-H. (2018). Nanoparticle-Mediated Combination Therapy: Two-in-One Approach for Cancer. Int. J. Mol. Sci., 19.10.3390/ijms19103264 ↗
27. Mousavi, S.M., Hashemi, S.A., Ghahramani, Y., Azhdari, R., Yousefi, K., Gholami, A., Fallahi Nezhad, F., Vijayakameswara Rao, N., Omidifar, N., and Chiang, W.-H. (2022). Antiproliferative and Apoptotic Effects of Graphene Oxide @AlFu MOF Based Saponin Natural Product on OSCC Line. Pharmaceuticals, 15.10.3390/ph15091137 ↗
28. Li, R., Gao, R., Zhao, Y., Zhang, F., Wang, X., Li, B., Wang, L., Ma, L., and Du, J. (2022). pH-Responsive Graphene Oxide Loaded with Targeted Peptide and Anticancer Drug for OSCC Therapy. Front. Oncol., 12.10.3389/fonc.2022.930920 ↗
29. Graphene Oxide Induces Autophagy and Apoptosis via the ROS-Dependent AMPK/mTOR/ULK-1 Pathway in Colorectal Cancer Cells10.2217/nnm-2022-0030 ↗
30. Bone Tissue Engineering via Carbon-Based Nanomaterials10.1002/adhm.201901495 ↗
31. Carbon-Based Nanomaterials for Bone and Cartilage Regeneration: A Review10.1021/acsbiomaterials.1c00759 ↗
32. Cyclin D1 in Oral Premalignant Lesions and Oral Squamous Cell Carcinoma: An Immunohistochemical Study10.4103/jomfp.JOMFP_164_20 ↗
33. Cyclin D1 Degradation Is Sufficient to Induce G1 Cell Cycle Arrest despite Constitutive Expression of Cyclin E2 in Ovarian Cancer Cells10.1158/0008-5472.CAN-09-0913 ↗
34. Schwock, J., Bradley, G., Ho, J.C., Perez-Ordonez, B., Hedley, D.W., Irish, J.C., and Geddie, W.R. (2010). SNAI1 Expression and the Mesenchymal Phenotype: An Immunohistochemical Study Performed on 46 Cases of Oral Squamous Cell Carcinoma. BMC Clin. Pathol., 10.10.1186/1472-6890-10-1 ↗
35. Marked Epithelial to Mesenchymal Transition in Surgical Margins of Oral Cancer-an in Vitro Study
36. Bera, S., Ghosh, S., Ali, A., Pal, M., and Chakrabarti, P. (2021). Inhibition of Microtubule Assembly and Cytotoxic Effect of Graphene Oxide on Human Colorectal Carcinoma Cell HCT116. Arch. Biochem. Biophys., 708.10.1016/j.abb.2021.108940 ↗
37. Synthesis, Characterization and Cytotoxic Evaluation of Graphene Oxide Nanosheets: In Vitro Liver Cancer Model
38. Graphene Oxide Inhibits Cell Migration and Invasion by Destroying Actin Cytoskeleton in Cervical Cancer Cells10.18632/aging.103821 ↗
39. Graphene Oxide and Reduced Graphene Oxide Induced Neural Pheochromocytoma-Derived PC12 Cell Lines Apoptosis and Cell Cycle Alterations via the ERK Signaling Pathways10.2147/IJN.S141032 ↗
40. Deciphering the Underlying Mechanisms of Oxidation-State Dependent Cytotoxicity of Graphene Oxide on Mammalian Cells10.1016/j.toxlet.2015.05.021 ↗
41. Activation of Apoptosis Signalling Pathways by Reactive Oxygen Species10.1016/j.bbamcr.2016.09.012 ↗
42. Reactive Oxygen Species (ROS) Control the Expression of Bcl-2 Family Proteins by Regulating Their Phosphorylation and Ubiquitination10.1111/j.1349-7006.2004.tb03323.x ↗
43. Protein Corona-Mediated Mitigation of Cytotoxicity of Graphene Oxide10.1021/nn200021j ↗
44. PI3K/AKT/mTOR Signaling Transduction Pathway and Targeted Therapies in Cancer10.1186/s12943-023-01827-6 ↗
45. HES1 in Immunity and Cancer10.1016/j.cytogfr.2016.03.010 ↗
46. In Vitro Toxicity of Carbon Nanotubes, Nano-Graphite and Carbon Black, Similar Impacts of Acid Functionalization10.1016/j.tiv.2015.09.014 ↗
47. Immunotoxicity Assessment of Ordered Mesoporous Carbon Nanoparticles Modified with PVP/PEG10.1016/j.colsurfb.2018.07.072 ↗
48. Cellular and Subcellular Interactions of Graphene-Based Materials with Cancerous and Non-Cancerous Cells10.1016/j.addr.2022.114467 ↗
49. Alteration of Apoptosis during Differentiation in Human Dental Pulp-Derived Mesenchymal Stem Cell10.12750/JARB.34.1.2 ↗
50. Graphene for Controlled and Accelerated Osteogenic Differentiation of Human Mesenchymal Stem Cells10.1021/nn200500h ↗
51. Kang, M.S., Jeong, S.J., Lee, S.H., Kim, B., Hong, S.W., Lee, J.H., and Han, D.-W. (2021). Reduced Graphene Oxide Coating Enhances Osteogenic Differentiation of Human Mesenchymal Stem Cells on Ti Surfaces. Biomater. Res., 25.10.1186/s40824-021-00205-x ↗
52. Basal Cell Carcinoma Stem Cells Exhibit Osteogenic and Chondrogenic Differentiation Potential10.32604/biocell.2021.015060 ↗
53. Single Walled Carbon Nanotube Composites for Bone Tissue Engineering10.1002/jor.22379 ↗