In Vitro Study of Anticancer Activity of Biosynthesized ZnO and Co-ZnO Nanoparticles on Human Brain Glioblastoma Cells
DOI:
https://doi.org/10.62382/bbw3ff89Keywords:
Cobalt doped zinc oxide, FESEM, U87, WST-1Abstract
A successful attempt was made to utilize leaf extract of Prosopis fracta for the environmentally friendly and straightforward synthesis of zinc oxide (ZnO) and cobalt-doped zinc oxide (Co-ZnO) nanoparticles. This synthesis was characterized using analytical techniques including field emission scanning electron microscopy (FESEM) and powder X-ray diffraction (PXRD). The presence of finely doped cobalt within the zinc oxide structure was confirmed by PXRD and energy dispersive X-ray (EDX) data. The FESEM analysis revealed a spherical morphology for both ZnO and Co-ZnO nanoparticles. The cytotoxicity of the synthesized nanoparticles was surveyed against brain glioblastoma cells (U87) through the WST-1 assay. Compared to the results obtained from pure nanoparticles, the doped nanoparticles demonstrated a significantly greater toxicity towards U87 cells. Experimental results presented that Co-ZnO nanoparticles created a pronounced cytotoxic impact. Thus, it concluded that doping process applied to ZnO nanoparticles enhanced their inhibitory effect on U87 cells.
References
[1]Vijayakumar S, Vaseeharan B, Malaikozhundan B, Shobiya M. Laurus nobilis leaf extract mediated green synthesis of ZnO nanoparticles: Characterization and biomedical applications. Biomedicine & Pharmacotherapy. 2016, 84, 1213-1222. DOI: 10.1016/j.biopha.2016.10.038
[2]Rehman H, Ali W, Zaman Khan N, Aasim M, Khan T, Ali Khan A. Delphinium uncinatum mediated biosynthesis of zinc oxide nanoparticles and in-vitro evaluation of their antioxidant, cytotoxic, antimicrobial, anti-diabetic, anti-inflammatory, and anti-aging activities. Saudi Journal of Biological Sciences. 2023, 30(1), 103485. DOI: 10.1016/j.sjbs.2022.103485
[3]Condello M, De Berardis B, Ammendolia MG, Barone F, Condello G, Degan P, et al. ZnO nanoparticle tracking from uptake to genotoxic damage in human colon carcinoma cells. Toxicology In Vitro. 2016, 35, 169-179. DOI: 10.1016/j.tiv.2016.06.005
[4]Al-Hamadani NHM, Pouresmaeil V, Sharbatiyan M, Tabrizi MH. Investigation into the anticancer activity of biosynthesized zinc oxide nanoparticles incorporating 6-gingerols. Cellular and Molecular Biomedical Reports. 2025, 5(3), 168-186. DOI: 10.55705/cmbr.2025.495731.1296
[5]Li Y, Li F, Zhang L, Zhang C, Peng H, Lan F, et al. Zinc oxide nanoparticles induce mitochondrial biogenesis impairment and cardiac dysfunction in human iPSC-derived cardiomyocytes. International Journal of Nanomedicine. 2020, 15, 2669-2683. DOI: 10.2147/IJN.S249912.
[6]Dash UC, Bhol NK, Swain SK, Samal RR, Nayak PK, Raina V, et al. Oxidative stress and inflammation in the pathogenesis of neurological disorders: Mechanisms and implications. Acta Pharmaceutica Sinica B. 2025, 15(1), 15-34. DOI: 10.1016/j.apsb.2024.10.004
[7]Harshita Sharma, Pawan K. Mishra, Sushama Talegaonkar, Bhuvaneshwar Vaidya. Metal nanoparticles: A theranostic nanotool against cancer. Drug Discovery Today. 2015, 20(9), 1143-1151. DOI: 10.1016/j.drudis.2015.05.009
[8]Sharma H, Kumar K, Choudhary C, Mishra PK, Vaidya B. Development and characterization of metal oxide nanoparticles for the delivery of anticancer drug. Artificial Cells, Nanomedicine, and Biotechnology. 2016, 44(2), 672-679. DOI: 10.3109/21691401.2014.978980
[9]Wang L, Guo D, Wang Z, Yin X, Wei H, Hu W, et al. Zinc oxide nanoparticles induce human tenon fibroblast apoptosis through reactive oxygen species and caspase signaling pathway. Archives of Biochemistry and Biophysics. 2020, 683, 108324. DOI: 10.1016/j.abb.2020.108324
[10]Su L, Li H, Wang J, Wu J, Wan J, He YF, et al. Zinc oxide nanoparticles cause hepatotoxicity in rare minnow (Gobiocypris rarus) via ROS-mediated oxidative stress and apoptosis activation and inhibition of lipid peroxidation. Aquaculture Reports. 2024, 38(5), 102317. DOI: 10.1016/j.aqrep.2024.102317
[11]Alarifi S, Ali D, Alkahtani S, Verma A, Ahamed M, Ahmed M, et al. Induction of oxidative stress, DNA damage, and apoptosis in a malignant human skin melanoma cell line after exposure to zinc oxide nanoparticles. International Journal of Nanomedicine. 2013, 8, 983-993. DOI: 10.2147/IJN.S42028
[12]Merighi A, Lossi L. Endoplasmic reticulum stress signaling and neuronal cell death. International Journal of Molecular Sciences. 2022, 23(23), 15186. DOI: 10.3390/ijms232315186
[13]Kosmulski M. The pH dependent surface charging and points of zero charge. X. Update. Advances in Colloid and Interface Science. 2023, 319, 102973. DOI: 10.1016/j.cis.2023.102973
[14]Arulkumar E, Thanikaikarasan S, Rajkumar S, Wondimu W. Influence of solution pH dependency on structure, optical with photoelectrochemical characteristics of SILAR deposited copper oxide thin films. Heliyon. 2024, 10(13), e33579. DOI: 10.1016/j.heliyon.2024.e33579
[15]Pajic-Lijakovic I, Milivojevic M. Surface activity of cancer cells: The fusion of two cell aggregates. Biocell. 2022, 47(1), 1-18. DOI: 10.48550/arXiv.2109.09424
[16]Vallabhapurapu SD, Blanco V, Sulzmaier L, Dunleavey J, Singh S, Chu ZT, et al. Variation in human cancer cell external phosphatidylserine is regulated by flippase activity and intracellular calcium. Oncotarget. 2015, 6, 34375-34388. DOI: 10.18632/oncotarget.6045
[17]Aksoy B, Atakan N, Aksoy HM, Tezel GG, Renda N, Ozkara HA, et al. Effectiveness of topical zinc oxide application on hypertrophic scar development in rabbits. Burns. 2010, 36(7), 1027-1035. DOI: 10.1016/j.burns.2010.01.020
[18]Chakraborti S, Chakraborty S, Saha S, Manna A, Banerjee S, Adhikary A, et al. PEG-functionalized zinc oxide nanoparticles induce apoptosis in breast cancer cells through reactive oxygen species-dependent impairment of DNA damage repair enzyme NEIL2. Free Radical Biology and Medicine. 2017, 103, 35-47. DOI: 10.1016/j.freeradbiomed.2016.11.048
[19]Namvar F, Azizi S, Rahman HS, Mohamad R, Rasedee A, Soltani M, et al. Green synthesis, characterization, and anticancer activity of hyaluronan/zinc oxide nanocomposite. OncoTargets and Therapy. 2016, 9, 4549-4559. DOI: 10.2147/OTT.S95962
[20]Kc B, Paudel SN, Rayamajhi S, Karna D, Adhikari S, Shrestha BG, et al. Enhanced preferential cytotoxicity through surface modification: synthesis, characterization and comparative in vitro evaluation of TritonX-100 modified and unmodified zinc oxide nanoparticles in human breast cancer cell (MDA-MB-231). Chemistry Central Journal. 2016, 10, 16. DOI: 10.1186/s13065-016-0162-3
[21]Mohamed SY, Elshoky HA, El-Sayed NM, Fahmy HM, Ali MA. Ameliorative effect of zinc oxide-chitosan conjugates on the anticancer activity of cisplatin: Approach for breast cancer treatment. International Journal of Biological Macromolecules. 2024, 257(Pt 1), 128597. DOI: 10.1016/j.ijbiomac.2023.128597
[22]Chandrasekaran M, Pandurangan M. In vitro selective anti-proliferative effect of zinc oxide nanoparticles against co-cultured C2C12 myoblastoma cancer and 3T3-L1 normal cells. Biological Trace Element Research. 2016, 172, 148-154. DOI: 10.1007/s12011-015-0562-6
[23]Quispe Cohaila AB, Fora Quispe GL, Cáceda Quiroz CJ, Mamani Anccasi R, Mejía García TA, Tamayo Calderón RM, et al. Biogenic ZnO nanoparticles synthesized by B. licheniformis: A selective cytotoxicity against NG-108 glioblastoma cells. Nanomaterials. 2025, 15(17), 1338. DOI: 10.3390/nano15171338
[24]Sukhodub L, Kumeda M, Sukhodub L, Vovchenko L, Prokopiuk V, Petrenko O, et al. Effect of zinc oxide micro- and nanoparticles on cytotoxicity, antimicrobial activity and mechanical properties of apatite-polymer osteoplastic material. Journal of the Mechanical Behavior of Biomedical Materials. 2024, 150, 106289. DOI: 10.1016/j.jmbbm.2023.106289
[25]Tseriotis VS, Ampazis D, Karachrysafi S, Papamitsou T, Petrakis G, Kouvelas D, et al. ZnO-based nanoparticles for targeted cancer chemotherapy and the role of tumor microenvironment: A systematic review. International Journal of Molecular Sciences. 2025, 26(17), 8417. DOI: 10.3390/ijms26178417
[26]Han Z, Wang XH, Heng CL, Han QS, Cai SF, Li JY, et al. Synergistically enhanced photocatalytic and chemotherapeutic effects of aptamer-functionalized ZnO nanoparticles towards cancer cells. Physical Chemistry Chemical Physics. 2015, 17, 21576-21582. DOI: 10.1039/c5cp02139a
[27]Ahmadi M, Ritter CA, von Woedtke T, Bekeschus S, Wende K. Package delivered: Folate receptor-mediated transporters in cancer therapy and diagnosis. Chemical Science. 2024, 15, 1966-2006. DOI: 10.1039/d3sc05539f
[28]Vimala K, Shanthi K, Sundarraj S, Kannan S. Synergistic effect of chemo-photothermal for breast cancer therapy using folic acid (FA) modified zinc oxide nanosheet. Journal of Colloid and Interface Science. 2017, 488, 92-108. DOI: 10.1016/j.jcis.2016.10.067
[29]Davis ME. Glioblastoma: Overview of disease and treatment. Clinical Journal of Oncology Nursing. 2016, 20(5 Suppl), S2-S8. DOI: 10.1188/16.CJON.S1.2-8
[30]Akter F, Simon B, de Boer NL, Redjal N, Wakimoto H, Shah K. Pre-clinical tumor models of primary brain tumors: Challenges and opportunities. Biochimica et Biophysica Acta - Reviews on Cancer. 2021, 1875(1), 188458. DOI: 10.1016/j.bbcan.2020.188458.
[31]Alifieris C, Trafalis DT. Glioblastoma multiforme: Pathogenesis and treatment. Pharmacology & Therapeutics. 2015, 152, 63-82. DOI: 10.1016/j.pharmthera.2015.05.005
[32]Mukhtar M, Bilal M, Rahdar A, Barani M, Arshad R, Behl T, et al. Nanomaterials for diagnosis and treatment of brain cancer: Recent updates. Chemosensors. 2020, 8(4), 117. DOI: 10.3390/chemosensors8040117
[33]Mohamed NA, Marei I, Crovella S, Abou-Saleh H. Recent developments in nanomaterials-based drug delivery and upgrading treatment of cardiovascular diseases. International Journal of Molecular Sciences. 2022, 23(3), 1404. DOI: 10.3390/ijms23031404
[34]Hamidian K, Sarani M, Sheikhi E, Khatami M. Cytotoxicity evaluation of green synthesized ZnO and Ag-doped ZnO nanoparticles on brain glioblastoma cells. Journal of Molecular Structure. 2022, 1251(1), 131962. DOI: 10.1016/j.molstruc.2021.131962
[35]Harish V, Tewari D, Gaur M, Yadav AB, Swaroop S, Bechelany M, et al. Review on nanoparticles and nanostructured materials: Bioimaging, biosensing, drug delivery, tissue engineering, antimicrobial, and agro-food applications. Nanomaterials. 2022, 12(3), 457. DOI: 10.3390/nano12030457
[36]Darroudi M, Hakimi M, Sarani M, Kazemi Oskuee R, Khorsand Zak A, Gholami L, et al. Facile synthesis, characterization, and evaluation of neurotoxicity effect of cerium oxide nanoparticles. Ceramics International. 2013, 39(6), 6917-6921. DOI: 10.1016/j.ceramint.2013.02.026
[37]Hoseini SJ, Darroudi M, Kazemi Oskuee R, Gholami L, Khorsand Zak A. Honey-based synthesis of ZnO nanopowders and their cytotoxicity effects. Advanced Powder Technology. 2015, 26(3), 991-996. DOI: 10.1016/j.apt.2015.04.003
[38]Abdul Salam H, Sivaraj R, Venckatesh R. Green synthesis and characterization of zinc oxide nanoparticles from Ocimum basilicum L. var. purpurascens Benth-Lamiaceae leaf extract. Materials Letters. 2014, 131, 16-18. DOI:10.1016/j.matlet.2014.05.033
[39]Fu L, Fu Z. Plectranthus amboinicus leaf extract-assisted biosynthesis of ZnO nanoparticles and their photocatalytic activity. Ceramics International. 2015, 41(2), 2492-2496. DOI: 10.1016/j.ceramint.2014.10.069
[40]Nethravathi PC, Shruthi GS, Suresh D, Udayabhanu, Nagabhushana H, Sharma S. Garcinia xanthochymus mediated green synthesis of ZnO nanoparticles: Photoluminescence, photocatalytic and antioxidant activity studies. Ceramics International. 2015, 41(7), 8680-8687. DOI: 10.1016/j.ceramint.2015.03.084
[41]Jayaseelan C, Rahuman AA, Kirthi AV, Marimuthu S, Santhoshkumar T, Bagavan A, et al. Novel microbial route to synthesize ZnO nanoparticles using Aeromonas hydrophila and their activity against pathogenic bacteria and fungi. Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy. 2012, 90, 78-84. DOI: 10.1016/j.saa.2012.01.006
[42]Mohammadi Dargah M, Pedram P, Cabrera-Barjas G, Delattre C, Nesic A, Santagata G, et al. Biomimetic synthesis of nanoparticles: A comprehensive review on green synthesis of nanoparticles with a focus on Prosopis farcta plant extracts and biomedical applications. Advances in Colloid and Interface Science. 2024, 332, 103277. DOI: 10.1016/j.cis.2024.103277
[43]Kundu D, Hazra C, Chatterjee A, Chaudhari A, Mishra S. Extracellular biosynthesis of zinc oxide nanoparticles using Rhodococcus pyridinivorans NT2: Multifunctional textile finishing, biosafety evaluation and in vitro drug delivery in colon carcinoma. Journal of Photochemistry and Photobiology B: Biology. 2014, 140, 194-204. DOI: 10.1016/j.jphotobiol.2014.08.001
[44]Azizi S, Ahmad MB, Namvar F, Mohamad R. Green biosynthesis and characterization of zinc oxide nanoparticles using brown marine macroalga Sargassum muticum aqueous extract. Materials Letters. 2014, 116, 275-277. DOI: 10.1016/j.matlet.2013.11.038
[45]Zamiri R, Parvizi R, Zakaria A, Sadrolhosseini AR, Zamiri G, Darroudi M, et al. Investigation on nonlinear-optical properties of palm oil/silver nanoparticles. Journal of the European Optical Society - Rapid Publications. 2012, 7, 12020. DOI: 10.2971/jeos.2012.12020
[46]Rosi NL, Mirkin CA. Nanostructures in biodiagnostics. Chemical Reviews. 2005, 105(4), 1547-1562. DOI: 10.1021/cr030067f
[47]Tania IS, Ali M. Coating of ZnO nanoparticle on cotton fabric to create a functional textile with enhanced mechanical properties. Polymers. 2021, 13(16), 2701. DOI: 10.3390/polym13162701
[48]Sangeetha G, Rajeshwari S, Venckatesh R. Green synthesis of zinc oxide nanoparticles by Aloe barbadensis miller leaf extract: Structure and optical properties. Materials Research Bulletin. 2011, 46(12), 2560-2566. DOI: 10.1016/j.materresbull.2011.07.046
[49]Massima Mouele ES, Tijani JO, Fatoba OO, Petrik LF. Degradation of organic pollutants and microorganisms from wastewater using different dielectric barrier discharge configurations - a critical review. Environmental Science and Pollution Research. 2015, 22(23), 18345-18362. DOI: 10.1007/s11356-015-5386-6
[50]Jeevanandam J, Barhoum A, Chan YS, Dufresne A, Danquah MK. Review on nanoparticles and nanostructured materials: History, sources, toxicity and regulations. Beilstein Journal of Nanotechnology. 2018, 9, 1050-1074. DOI: 10.3762/bjnano.9.98
[51]Jiang J, Pi J, Cai J. The advancing of zinc oxide nanoparticles for biomedical applications. Bioinorganic Chemistry and Applications. 2018, 2018(3), 1-18. DOI: 10.1155/2018/1062562
[52]Rama Narsimha Reddy A, Srividya L. Evaluation of in vitro cytotoxicity of zinc oxide (ZnO) nanoparticles using human cell lines. Journal of Toxicology and Risk Assessment. 2018, 4(1), 009. DOI: 10.23937/2572-4061.1510009
[53]Miri A, Sarani M. Biosynthesis and cytotoxic study of synthesized zinc oxide nanoparticles using Salvadora persica. BioNanoScience. 2019, 9, 164-171. DOI: 10.1007/s12668-018-0579-3
[54]Nemati S, Hosseini HA, Hashemzadeh A, Mohajeri M, Sabouri Z, Darroudi M, et al. Cytotoxicity and photocatalytic applications of biosynthesized ZnO nanoparticles by Rheum turketanicum rhizome extract. Materials Research Express. 2019, 6(12), 125016. DOI: 10.1088/2053-1591/ab46fb
[55]Akhtar MJ, Alhadlaq HA, Alshamsan A, Majeed Khan MA, Ahamed M. Aluminum doping tunes band gap energy level as well as oxidative stress-mediated cytotoxicity of ZnO nanoparticles in MCF-7 cells. Scientific Reports. 2015, 5, 13876. DOI: 10.1038/srep13876
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