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Unravelling the DNA Binding Interactions and Genotoxicity of Cerium Sulfide Nanoparticles

S Farhat Afsar, Chandra Prabha M N, D L Monika, R Hari Krishna

Abstract


Metal sulfide nanoparticles (NPs) are extensively explored for biomedical applications, yet their interactions with DNA are essential for evaluating their biological safety. The DNA-binding and genotoxic potential of cerium sulfide NPs (Ce₂S₃ NPs) remain poorly defined.  This study evaluates the interaction of solvothermally synthesized Ce₂S₃ NPs with calf thymus DNA (CT-DNA) and their genotoxic effects using complementary spectroscopic, electrochemical, and biological approaches. X-ray diffraction (XRD), Fourier-transform infrared spectroscopy (FTIR), field-emission scanning electron microscopy (FE-SEM), and transmission electron microscopy (TEM) revealed a wurtzite crystal structure with particle sizes of 16 - 40 nm. Surface charge measurements indicated a point of zero charge (pHₚzc) of 6, consistent with protonation under acidic conditions and deprotonation under basic conditions, providing complementary evidence for the electrostatic interaction between DNA and the Ce₂S₃ NPs. UV–visible spectroscopy revealed a hypochromic effect, with a binding constant (Kb) of 5.19 × 10⁴ M⁻¹, indicating moderate DNA-binding affinity. Fluorescence quenching yielded a Stern-Volmer constant (Ksv) of 1.57 × 10⁴ M⁻¹ and a Kb of 6.71 × 10⁶ M⁻¹, consistent with predominantly through static quenching. Circular dichroism (CD) spectroscopy confirmed retention of the native B-form of CT-DNA, indicating non-intercalative binding. Cyclic voltammetry suggested an electrostatic, with an estimated Kb of 1.70 × 10⁴ M⁻¹. Comet assay revealed dose-dependent DNA damage: limited genotoxicity at lower Ce₂S₃ NPs concentrations, and increased DNA damage at higher concentrations. These findings indicate a concentration-dependent transition from relatively limited DNA interactions at lower concentrations to detectable genotoxic effects at higher concentrations, suggesting the need for dose optimization to ensure their safe and effective use in biomedical applications.

Keywords



[1] V. Ramalingam, S. Raja, S. Sundaramahalingam, and R. Rajaram, “Chemical fabrication of graphene oxide nanosheets attenuates biofilm formation of human clinical pathogens,” Bioorganic Chemistry, vol. 83, pp. 326–335, Mar. 2019, doi: 10.1016/j.bioorg.2018.10.052.

[2] L. L. Tayo, “Stimuli-responsive nanocarriers for intracellular delivery,” Biophysical Reviews, vol. 9, no. 6, pp. 931–940, Nov. 2017, doi: 10.1007/s12551-017-0341-z.

[3] S. Islam et al., “Nanomaterials: applications in biomedicine and biotechnology,” in Handbook of Nanomaterials and Nanocomposites for Energy and Environmental Applications, Cham: Springer, pp. 1–18, Aug. 2020, doi: 10.1007/978-3-030-11155-7_4-1.

[4] H. Verma, M. Aggarwal, and S. Kumar, “Opportunities and significance of nanoparticle–DNA binding in medical biotechnology: a review,” Cureus, vol. 14, no. 11, Nov. 2022, Art. no. e31005, doi: 10.7759/cureus.31005.

[5] S. Anjum et al., “Emerging applications of nanotechnology in healthcare systems: grand challenges and perspectives,” Pharmaceuticals, vol. 14, no. 8, Jul. 2021, Art. no. 707, doi: 10.3390/ph14080707.

[6] U. Singh et al., “DNA-functionalized nanoparticles for targeted biosensing and biological applications,” ACS Omega, vol. 5, no. 48, pp. 30767–30774, Nov. 2020, doi: 10.1021/acsomega.0c03656.

[7] M. Sirajuddin, S. Ali, and A. Badshah, “Drug–DNA interactions and their study by UV–Visible, fluorescence spectroscopies and cyclic voltametry,” Journal of Photochemistry and Photobiology B: Biology, vol. 124, pp. 1–19, Jul. 2013, doi: 10.1016/j.jphotobiol.2013.03.013.

[8] S. U. Rehman, T. Sarwar, M. A. Husain, H. M. Ishqi, and M. Tabish, “Studying non-covalent drug–DNA interactions,” Archives of Biochemistry and Biophysics, vol. 576, pp. 49–60, Jun. 2015, doi: 10.1016/j.abb.2015.03.024.

[9] X.-L. Li, Y.-J. Hu, H. Wang, B.-Q. Yu, and H.-L. Yue, “Molecular spectroscopy evidence of berberine binding to DNA: comparative binding and thermodynamic profile of intercalation,” Biomacromolecules, vol. 13, no. 3, pp. 873–880, Feb. 2012, doi: 10.1021/bm2017959.

[10] M. Saeed et al., “Comprehensive reviews on the potential applications of inorganic metal sulfide nanostructures in biological, environmental, healthcare, and energy generation and storage,” Reviews in Inorganic Chemistry, vol. 45, no. 2, pp. 237–274, May. 2024, doi: 10.1515/revic-2024-0016.

[11] W. Fei et al., “Engineering of bioactive metal sulfide nanomaterials for cancer therapy,” Journal of Nanobiotechnology, vol. 19, no. 1, Mar. 2021, Art. no. 93, doi: 10.1186/s12951-021-00839-y.

[12] M. Mahanthappa, M. A. Savanur, and S. Yellappa, “Molecular interaction studies of zinc sulphide nanoparticles with DNA and its consequence: a multitechnique approach,” Luminescence, vol. 36, no. 1, pp. 45–56, Jul. 2020, doi: 10.1002/bio.3912.

[13] H. Kumar et al., “Antioxidant functionalized nanoparticles: a combat against oxidative stress,” Nanomaterials, vol. 10, no. 7, Jul. 2020, Art. no. 1334, doi: 10.3390/nano10071334.

[14] A. Shetty, H. Lang, and S. Chandra, “Metal sulfide nanoparticles for imaging and phototherapeutic applications,” Molecules, vol. 28, no. 6, Mar. 2023, Art. no. 2553, doi: 10.3390/molecules28062553.

[15] S. Das, J. M. Dowding, K. E. Klump, J. F. McGinnis, W. Self, and S. Seal, “Cerium oxide nanoparticles: applications and prospects in nanomedicine,” Nanomedicine, vol. 8, no. 9, pp. 1483–1508, Aug. 2013, doi: 10.2217/nnm.13.133.

[16] S. A. Abdulsattar, “Cerium oxide nanoparticles role as antioxidant,” Medical Journal of Babylon, vol. 21, no. 2, pp. 235–239, Jul. 2024, doi: 10.4103/MJBL.MJBL_1022_23.

[17] Y. Wu and H. T. Ta, “Different approaches to synthesising cerium oxide nanoparticles and their corresponding physical characteristics, and ROS scavenging and anti-inflammatory capabilities,” Journal of Materials Chemistry B, vol. 9, no. 36, pp. 7291–7301, Jul. 2021, doi: 10.1039/d1tb01091c.

[18] A. L. Chibac-Scutaru, V. Podasca, I. A. Dascalu, and V. Melinte, “Exploring the influence of synthesis parameters on the optical properties for various CeO2 NPs,” Nanomaterials, vol. 12, no. 9, Apr. 2022, Art no. 1402, doi: 10.3390/nano12091402.

[19] R. Liman, Y. Acikbas, and İ. H. Ciğerci, “Cytotoxicity and genotoxicity of cerium oxide micro and nanoparticles by Allium and Comet tests,” Ecotoxicology and Environmental Safety, vol. 168, pp. 408–414, Jan. 2019, doi: 10.1016/j.ecoenv.2018.10.088.

[20] C. Sambathkumar, N. Nallamuthu, M. K. Kumar, S. Sudhahar, and P. Devendran, “Electrochemical exploration of cobalt sulfide nanoparticles synthesis using cobalt diethyldithiocarbamate as single source precursor for hybrid supercapacitor device,” Journal of Alloys and Compounds, vol. 920, Nov. 2022, Art. no. 165839, doi: 10.1016/j.jallcom.2022.165839.

[21] Q. Wang, S.-R. Zhang, and X. Ji, “Investigation of interaction of antibacterial drug sulfamethoxazole with human serum albumin by molecular modeling and multi-spectroscopic method,” Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy, vol. 124, pp. 84–90, Apr. 2014, doi: 10.1016/j.saa.2013.12.100.

[22] G. Lucena-Aguilar, A. M. Sánchez-López, C. Barberán-Aceituno, J. A. Carrillo-Ávila, J. A. López-Guerrero, and R. Aguilar-Quesada, “DNA source selection for downstream applications based on DNA quality indicators analysis,” Biopreservation and Biobanking, vol. 14, no. 4, pp. 264–270, May. 2016, doi: 10.1089/bio.2015.0064.

[23] A. Yadav, N. Bagotia, S. Yadav, A. K. Sharma, and S. Kumar, “Adsorptive studies on the removal of dyes from single and binary systems using Saccharum munja plant-based novel functionalized CNT composites,” Environmental Technology & Innovation, vol. 24, Nov. 2021, Art. no. 102015, doi: 10.1016/j.eti.2021.102015.

[24] S. Dan, A. Chattree, J. Naskar, and S. Kamsonlian, “Comparative study of ferromagnetic behaviour in bare and DDMAB-PMMA-PEG modified Manganese Ferrite (MnFe2O4) nanoparticles,” Materials Today: Proceedings, vol. 78, pp. 62–68, 2023, doi: 10.1016/j.matpr.2022.11.197.

[25] M. A. Husain, H. M. Ishqi, T. Sarwar, S. U. Rehman, and M. Tabish, “Interaction of indomethacin with calf thymus DNA: a multi-spectroscopic, thermodynamic and molecular modelling approach,” Medchemcomm, vol. 8, no. 6, pp. 1283–1296, Apr. 2017, doi: 10.1039/c7md00094d.

[26] L. Momeni, B. Shareghi, A. A. Saboury, and S. Farhadian, “Comparative studies on the interaction of spermidine with bovine trypsin by multispectroscopic and docking methods,” The Journal of Physical Chemistry B, vol. 120, no. 36, pp. 9632–9641, Sep. 2016, doi: 10.1021/acs.jpcb.6b06648.

[27] N. Yadav, A. Singh, and M. Kaushik, “Synthesis and characterization of hydrothermally synthesized superparamagnetic APTS–ZnFe2O4 nanoparticles: DNA binding studies for exploring biomedical applications,” Chemical Papers, vol. 74, pp. 1177–1188, Oct. 2019, doi: 10.1007/s11696-019-00953-0.

[28] S. Nandhakumar, S. Parasuraman, M. M. Shanmugam, K. R. Rao, P. Chand, and B. V. Bhat, “Evaluation of DNA damage using single-cell gel electrophoresis (Comet Assay),” Journal of Pharmacology and Pharmacotherapeutics, vol. 2, no. 2, pp. 107–111, Jun. 2011, doi: 10.4103/0976-500X.81903.

[29] P. Velumani, N. Palani, A. A. Casmie, R. Senthilvel, and V. Parthasarthy, “Cellular and chromosomal interaction of bio-synthesized copper oxide nanoparticles - Induced nano-cytotoxicity and genotoxicity,” Toxicology in Vitro, vol. 104, Apr. 2025, Art. no. 106000, doi: 10.1016/j.tiv.2024.106000.

[30] M. Javed, I. Ahmad, A. Ahmad, N. Usmani, and M. Ahmad, “Studies on the alterations in haematological indices, micronuclei induction and pathological marker enzyme activities in Channa punctatus (spotted snakehead) perciformes, channidae exposed to thermal power plant effluent,” SpringerPlus, vol. 5, no. 1, Jun. 2016, Art. no. 761, doi: 10.1186/s40064-016-2478-9.

[31] A. Singh, Neelam, and M. Kaushik, “Physicochemical investigations of zinc oxide nanoparticles synthesized from Azadirachta Indica (Neem) leaf extract and their interaction with Calf-Thymus DNA,” Results in Physics, vol. 13, Jun. 2019, Art. no. 102168, doi: 10.1016/j.rinp.2019.102168.

[32] M. M. Rahman, J. Ahmed, and A. M. Asiri, “A glassy carbon electrode modified with γ-Ce 2 S 3 -decorated CNT nanocomposites for uric acid sensor development: a real sample analysis,” RSC Advances, vol. 7, no. 24, pp. 14649–14659, Mar. 2017, doi: 10.1039/c6ra27414e.

[33] S. K. Sahu, S. Sikdar, M. K. Ghosh, and T. K. Ghorai, “Investigation of photocatalytic and DNA interaction of novel heterostructured GO/Bi2O3/ZnO nanocomposite,” Materials Science for Energy Technologies, vol. 5, pp. 324–333, 2022, doi: 10.1016/j.mset.2022.07.002.

[34] P. Mohanasundaram and M. Saral A., “Binding properties and biological applications of green synthesized ZnO nanoparticles from neem flower,” Scientific Reports, vol. 15, no. 1, May. 2025, Art. no. 17727, doi: 10.1038/s41598-025-02157-x.

[35] H. N. Umh and Y. Kim, “Sensitivity of nanoparticles’ stability at the point of zero charge (PZC),” Journal of Industrial and Engineering Chemistry, vol. 20, no. 5, pp. 3175–3178, Sep. 2014, doi: 10.1016/j.jiec.2013.11.062.

[36] C. Benmouhoub, M. Turmine, A. Kadri, and A. Pailleret, “Influence of dodecylsulfate adsorption on the stability of cerium oxide nanoparticle-based colloidal aqueous dispersions,” Langmuir, vol. 36, no. 48, pp. 14563–14572, Nov. 2020, doi: 10.1021/acs.langmuir.0c02317.

[37] S. Das, S. Chatterjee, S. Pramanik, P. S. Devi, and G. S. Kumar, “A new insight into the interaction of ZnO with calf thymus DNA through surface defects,” Journal of Photochemistry and Photobiology B: Biology, vol. 178, pp. 339–347, Jan. 2018, doi: 10.1016/j.jphotobiol.2017.10.039.

[38] L. A. Tavadyan et al., “Exploring the interaction of ethidium bromide and HOECHST 33258 with DNA by means of electrochemical approach,” Biophysical Reviews and Letters, vol. 12, no. 3, pp. 151–161, Aug. 2017, doi: 10.1142/S1793048017500084.

[39] Í. P. Caruso, W. Vilegas, L. C. de Oliveira, and M. L. Cornélio, “Fluorescence spectroscopic and dynamics simulation studies on isoorientin binding with human serum albumin,” Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy, vol. 228, Mar. 2020, Art. no. 117738, doi: 10.1016/j.saa.2019.117738.

[40] S. Patel, P. Patel, and S. R. Bakshi, “Titanium dioxide nanoparticles: an in vitro study of DNA binding, chromosome aberration assay, and comet assay,” Cytotechnology, vol. 69, no. 2, pp. 245–263, Jan. 2017, doi: 10.1007/s10616-016-0054-3.

[41] N. Shehata, E. Samir, and I. Kandas, “Gold/QDs-Embedded-Ceria nanoparticles: optical fluorescence enhancement as a quenching sensor,” Applied Sciences, vol. 10, no. 4, Feb. 2020, Art. no. 1236, doi: 10.3390/app10041236.

[42] E. P. Babu et al., “Extracellularly synthesized ZnO nanoparticles interact with DNA and augment gamma radiation induced DNA damage through reactive oxygen species,” RSC Advances, vol. 5, no. 76, pp. 62067–62077, Jul. 2015, doi: 10.1039/c5ra09935h.

[43] S. Huang, F. Zhu, Q. Xiao, Y. Liang, Q. Zhou, and W. Su, “Thermodynamic investigation of the interaction between the [(η 6 -p-cymene)Ru(benzaldehyde-N 4 -phenylthiosemicarbazone)Cl]Cl anticancer drug and ctDNA: multispectroscopic and electrochemical studies,” RSC Advances, vol. 5, no. 53, pp. 42889–42902, 2015, doi: 10.1039/c5ra03979g.

[44] P. J. Villanueva et al., “Pyronaridine exerts potent cytotoxicity on human breast and hematological cancer cells through induction of apoptosis,” PLoS ONE, vol. 13, no. 11, Nov. 2018, Art. no. e0206467, doi: 10.1371/journal.pone.0206467.

[45] M. B. Gholivand, H. Peyman, Kh. Gholivand, H. Roshanfekr, A. A. Taherpour, and R. Yaghobi, “Theoretical and instrumental studies of the competitive interaction between aromatic α-Aminobisphosphonates with DNA using binding probes,” Applied Biochemistry and Biotechnology, vol. 182, no. 3, pp. 925–943, Jan. 2017, doi: 10.1007/s12010-016-2371-6.

[46] N. Arshad and S. I. Farooqi, “Cyclic voltammetric DNA binding investigations on some anticancer potential metal complexes: a review,” Applied Biochemistry and Biotechnology, vol. 186, no. 4, pp. 1090–1110, Jun. 2018, doi: 10.1007/s12010-018-2818-z.

[47] N. Arshad, M. H. Bhatti, S. I. Farooqi, S. Saleem, and B. Mirza, “Synthesis, photochemical and electrochemical studies on triphenyltin(IV) derivative of (Z)-4-(4-cyanophenylamino)-4-oxobut-2-enoic acid for its binding with DNA: Biological interpretation,” Arabian Journal of Chemistry, vol. 9, no. 3, pp. 451–462, May. 2016, doi: 10.1016/j.arabjc.2014.08.018.

[48] R. Hajian, P. Hossaini, Z. Mehrayin, P. M. Woi, and N. Shams, “DNA-binding studies of valrubicin as a chemotherapy drug using spectroscopy and electrochemical techniques,” Journal of Pharmaceutical Analysis, vol. 7, no. 3, pp. 176–180, Jun. 2017, doi: 10.1016/j.jpha.2017.01.003.

[49] S. Könen-Adıgüzel and S. Ergene, “In vitro evaluation of the genotoxicity of CeO2 nanoparticles in human peripheral blood lymphocytes using cytokinesis-block micronucleus test, comet assay, and gamma H2AX,” Toxicology and Industrial Health, vol. 34, no. 5, pp. 293–300, Mar. 2018, doi: 10.1177/0748233717753780.

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DOI: 10.14416/j.asep.2026.10.001

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