Evaluation of Cherenkov-induced photodynamic therapy of biohybrid photosensitive graphene oxide nanoplatform in cervical cancer cells

Articles in Press

Document Type : Original Article

Authors

1 Medical Physics Research Center, Basic Sciences Research Institute, Mashhad University of Medical Sciences, Mashhad, Iran

2 Department of Medical Physics, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

3 Pharmacological Research Center of Medicinal Plants, Mashhad University of Medical Sciences, Mashhad, Iran

4 Department of Pharmacology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

10.22038/ijbms.2025.86535.18694

Abstract

Objective(s): During radiotherapy, weak photons of Cherenkov radiation are generated, which can cause a relative increase in tumor resistance and cause errors in the radiotherapy treatment planning process. In this study, we used a photosensitive biohybrid graphene oxide nanostructure (GO-BSA-CTAB-PpIX) to maximize the absorption of Cherenkov photons in a broader range of emission wavelengths in order to create the induced photodynamic effect resulting from Cherenkov radiation.
Materials and Methods: TIn the first stage, after the synthesis and surface activation of the graphene oxide nanostructure by EDC, NHS, and albumin, its conjugation process with PpIX was performed. In the second step, it was characterized using an ultraviolet-visible spectrophotometer, dynamic light scattering, Fourier transform infrared spectroscopy, X-ray energy diffraction spectroscopy, and field emission scanning electron microscopy. In the third step, nanodosimetry was performed to prove the Cherenkov-induced photodynamic phenomenon. Finally, in vitro cellular studies were performed on the HeLa cell line (cervical cancer). The survival rate of different groups was measured using multiple MTT tests (24 to 72 hr), and the final results were statistically analyzed using GraphPad Prism software.
Results: The results show that the GO-BSA-CTAB-PpIX biohybrid nanostructure can be capable of generating various types of free radicals resulting from photodynamic therapy. This nanostructure inhibits cell growth by disrupting the cellular repair process through natural Cherenkov radiation during radiotherapy and creating an associated photodynamic effect (P<0.05).
Conclusion: Cherenkov radiation-based photodynamic therapy is a promising approach to address the challenges of photodynamic therapy and radiotherapy for cervical cancer.

Keywords

Main Subjects

References

1. AziziKia H, Didar H, Teymourzadeh A, Nakhostin-Ansari A, Jafari Doudaran P, Farasati Far B, et al. Uterine and cervical cancer in iran: An epidemiologic analysis of the iranian national population-based cancer registry. Arch Iran Med 2023; 26:1-7.
2.WHO. Cervical cancer 2022. Available from: https://www.who.int/health-topics/cervical-cancer#tab=tab_1.
3. McGraw SL, Ferrante JM. Update on prevention and screening of cervical cancer. World J Clin Oncol 2014; 5:744-752.
4. Sharma S, Deep A, Sharma AK. Current treatment for cervical cancer: An update. Anticancer Agents Med Chem 2020; 20:1768-1779.
5. Kwiatkowski S, Knap B, Przystupski D, Saczko J, Kędzierska E, Knap-Czop K, et al. Photodynamic therapy - mechanisms, photosensitizers and combinations. Biomed Pharmacother 2018; 106:1098-1107.
6. Panetta JV, Cvetkovic D, Chen X, Chen L, Ma CC. Radiodynamic therapy using 15-MV radiation combined with 5-aminolevulinic acid and carbamide peroxide for prostate cancer in vivo. Phys Med Biol 2020; 65:165008.
7. Sun B, Bte Rahmat JN, Zhang Y. Advanced techniques for performing photodynamic therapy in deep-seated tissues. Biomaterials 2022; 291:121875.
8. Casas A. Clinical uses of 5-aminolaevulinic acid in photodynamic treatment and photodetection of cancer: A review. Cancer Lett 2020; 490:165-173.
9. Huis In ‘t Veld RV, Heuts J, Ma S, Cruz LJ, Ossendorp FA, Jager MJ. Current challenges and opportunities of photodynamic therapy against cancer. Pharmaceutics 2023; 15:330-370.
10. Ciarrocchi E, Belcari N. Cerenkov luminescence imaging: Physics principles and potential applications in biomedical sciences. EJNMMI Physics 2017; 4:14-44.
11. Tzerkovsky D, Mazurenko A, Borychevsky F, Shashkouski D. Radiodynamic therapy with photosensitizers: Mini-review of experimental and clinical studies. J Anal Oncol 2022; 11:79-85.
12. Tapley ND, Fletcher GH. Patterns of use of 6-18 mev. electron beam radiation therapy. Am J Roentgenol Radium Ther Nucl Med 1967; 99:924-931.
13. Liu N, Su X, Sun X. Cerenkov radiation-activated probes for deep cancer theranostics: A review. Theranostics 2022; 12:7404-7419.
14. Shaffer TM, Pratt EC, Grimm J. Utilizing the power of Cerenkov light with nanotechnology. Nat Nanotechnol 2017; 12:106-117.
15. Einafshar E, Haghighi Asl A, hasheminia A, Malekzadeh A, Ramezani M. Synthesis of new biodegradable nanocarriers for SN38 delivery and synergistic phototherapy. Nanomed J 2018; 5:210-216.
16. Einafshar E, Ghorbani A. Advances in black phosphorus quantum dots for cancer research: Synthesis, characterization, and applications. Top Curr Chem 2024; 382:25.
17. Liu S, Zeng TH, Hofmann M, Burcombe E, Wei J, Jiang R, et al. Antibacterial activity of graphite, graphite oxide, graphene oxide, and reduced graphene oxide: Membrane and oxidative stress. ACS Nano 2011; 5:6971-6980.
18. Chartarrayawadee W, Moulton SE, Too CO, Wallace GG. Fabrication of graphene electrodes by electrophoretic deposition and their synergistic effects with PEDOT and platinum. Chiang Mai J Sci 2013; 40:750-762.
19. Joshi S, Singh H, Sharma S, Barman P, Saini A, Verma G. Synthesis and characterization of graphene oxide-bovine serum albumin conjugate membrane for adsorptive removal of Cobalt(II) from water. Int J Environ Sci Technol 2021; 18:3915-3928.
20. Retnakumari A, Setua S, Menon D, Ravindran P, Muhammed H, Pradeep T, et al. Molecular-receptor-specific, non-toxic, near-infrared-emitting Au cluster-protein nanoconjugates for targeted cancer imaging. Nanotechnology 2009; 21:055103.
21. Einafshar E, Khodadadipoor Z, Nejabat M, Ramezani M. Synthesis, characterization and application of α, β, and γ cyclodextrin-conjugated graphene oxide for removing cadmium ions from aqueous media. J Polym Environ 2021; 29:3161-3173.
22. Lutz H, Eckers W, Haeuseler H. OH stretching frequencies of solid hydroxides and of free OH− ions. J Mol Struct 1982; 80:221-224.
23. Kumar N, Das S, Bernhard C, Varma GD. Effect of graphene oxide doping on superconducting properties of bulk MgB2. Supercond Sci Technol 2013; 26:095008.
24. Einafshar E, Asl AH, Nia AH, Mohammadi M, Malekzadeh A, Ramezani M. New cyclodextrin-based nanocarriers for drug delivery and phototherapy using an irinotecan metabolite. Carbohydr Polym 2018; 194:103-110.
25. Dibona-Villanueva L, Fuentealba D. Protoporphyrin IX–chitosan oligosaccharide conjugate with potent antifungal photodynamic activity. J Agric Food Chem 2022; 70:9276-9282.
26. Shettigar RR, Misra NM, Patel K. Cationic surfactant (CTAB) a multipurpose additive in polymer-based drilling fluids. J Pet Explor Prod Technol 2018; 8:597-606.
27. Su G, Yang C, Zhu J-J. Fabrication of gold nanorods with tunable longitudinal surface plasmon resonance peaks by reductive dopamine. Langmuir 2015; 31:817-823.
28. Golestan H, Gharebaghi S, Tavana S, Vahdat-Farimani K, Modaresi Z, Chamani J. Preparation of cellulose nano crystals from cinnamon stick, curcumin delivery and interaction with human hemoglobin protein: A novel view of the oxygenation hemoglobin. J Mol Struct 2025; 1322:140626.
29. Kim H, Chung K, Lee S, Kim DH, Lee H. Near‐infrared light‐responsive nanomaterials for cancer theranostics. Wiley Interdiscip Rev Nanomed Nanobiotechnol 2016; 8:23-45.
30. Ghawanmeh AA, Ali GA, Algarni H, Sarkar SM, Chong KF. Graphene oxide-based hydrogels as a nanocarrier for anticancer drug delivery. Nano Res 2019; 12:973-990.
31. Zhu YJ, Chen F. pH‐responsive drug‐delivery systems. Chem Asian J  2015; 10:284-305.
32. Kamaly N, Yameen B, Wu J, Farokhzad OC. Degradable controlled-release polymers and polymeric nanoparticles: Mechanisms of controlling drug release. Chem Rev 2016; 116:2602-2663.
33. Yang K, Feng L, Liu Z. Stimuli responsive drug delivery systems based on nano-graphene for cancer therapy. Adv Drug Deliv Rev 2016; 105:228-241.
34. Yang X, Zhang X, Liu Z, Ma Y, Huang Y, Chen Y. High-efficiency loading and controlled release of doxorubicin hydrochloride on graphene oxide. J Phys Chem C 2008; 112:17554-17558.
35. Rajasekar P, Rao G, Kumar AS, Prakash J, Rathinasabapathi P, Venkatasubbu GD. Interaction of BSA with graphene oxide: Influence on the bioactivity of graphene oxide. Diam Relat Mater 2023; 132:109629.
36. Bashiri G, Padilla MS, Swingle KL, Shepherd SJ, Mitchell MJ, Wang K. Nanoparticle protein corona: From structure and function to therapeutic targeting. Lab Chip 2023; 23:1432-1466.
37. Jahanban-Esfahlan A, Ostadrahimi A, Jahanban-Esfahlan R, Roufegarinejad L, Tabibiazar M, Amarowicz R. Recent developments in the detection of bovine serum albumin. Int J Biol Macromol 2019; 138:602-617.
38. Sivaselvam S, Mohankumar A, Thiruppathi G, Sundararaj P, Viswanathan C, Ponpandian N. Engineering the surface of graphene oxide with bovine serum albumin for improved biocompatibility in Caenorhabditis elegans. Nanoscale Adv 2020; 2:5219-5230.
39. Kalhori F, Yazdyani H, Khademorezaeian F, Hamzkanloo N, Mokaberi P, Hosseini S, et al. Enzyme activity inhibition properties of new cellulose nanocrystals from Citrus medica L. pericarp: A perspective of cholesterol lowering. Luminescence 2022; 37:1836-1845.
40. Zhang Q, Xiao G, Sun Q, Zeng J, Wang L, Chen L, et al. Investigation of the mechanisms of radio-dynamic therapy. Mathews J Cancer Sci 2020; 5:1-9.
41. Liu Y, Zhang P, Li F, Jin X, Li J, Chen W, et al. Metal-based nanoenhancers for future radiotherapy: Radiosensitizing and synergistic effects on tumor cells. Theranostics 2018; 8:1824-1849.
42. Wang K, Zeng J, Luo L, Yang J, Chen J, Li B, et al. Identification of a cancer stem cell-like side population in the HeLa human cervical carcinoma cell line. Oncol Lett 2013; 6:1673-1680.
43. Golovynska I, Golovynskyi S, Qu J. Comparing the impact of NIR, visible and UV light on ROS upregulation via photoacceptors of mitochondrial complexes in normal, immune and cancer cells. Photochem Photobiol 2023; 99:106-119.
44. Di Fiore R, Suleiman S, Drago-Ferrante R, Subbannayya Y, Pentimalli F, Giordano A, et al. Cancer stem cells and their possible implications in cervical cancer: A short review. Int J Mol Sci 2022; 23: 5167-5184.
45. Organista-Nava J, Gómez-Gómez Y, Garibay-Cerdenares OL, Leyva-Vázquez MA, Illades-Aguiar B. Cervical cancer stem cell-associated genes: Prognostic implications in cervical cancer. Oncol Lett 2019; 18:7-14.
46. Fiorillo M, Verre AF, Iliut M, Peiris-Pagés M, Ozsvari B, Gandara R, et al. Graphene oxide selectively targets cancer stem cells, across multiple tumor types: implications for non-toxic cancer treatment, via “differentiation-based nano-therapy”. Oncotarget 2015; 6:3553-3562.
47. Oda Y, Bikle DD. Vitamin D and calcium signaling in epidermal stem cells and their regeneration. World J Stem Cells 2020; 12:604-611.
48. Papa V, Furci F, Minciullo PL, Casciaro M, Allegra A, Gangemi S. Photodynamic therapy in cancer: Insights into cellular and molecular pathways. Curr Issues Mol Biol 2025; 47:69-103.
49. Malek-Esfandiari Z, Rezvani-Noghani A, Sohrabi T, Mokaberi P, Amiri-Tehranizadeh Z, Chamani J. Molecular dynamics and multi-spectroscopic of the interaction behavior between bladder cancer cells and calf thymus DNA with rebeccamycin: Apoptosis through the down regulation of PI3K/AKT signaling pathway. J Fluoresc 2023; 33:1537-1557.
50. Jelley JV. Cerenkov radiation and its applications. Bri J Appl Phys 1955; 6:227-Last page.
51. Tendler, II, Hartford A, Jermyn M, LaRochelle E, Cao X, Borza V, et al. Experimentally observed cherenkov light generation in the eye during radiation therapy. Int J Radiat Oncol Biol Phys 2020; 106:422-429.
Iranian Journal of Basic Medical Sciences

Articles in Press, Accepted Manuscript
Available Online from 09 July 2025

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