{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T13:09:09Z","timestamp":1791896949699,"version":"4.3.4"},"reference-count":92,"publisher":"Public Library of Science (PLoS)","issue":"10","license":[{"start":{"date-parts":[[2025,10,23]],"date-time":"2025-10-23T00:00:00Z","timestamp":1761177600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Deanship of Scientific Research, Vice Presidency for Graduate Studies and Scientific Research","award":["KFU252911"],"award-info":[{"award-number":["KFU252911"]}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:p>\n                    The environmentally sustainable synthesis of nanoparticles has arisen as a viable alternative to traditional methods, tackling ecological and economic issues. This research investigates the green synthesis of ZnO nanoparticles utilizing an aqueous extract of\n                    <jats:italic>\n                      <jats:italic>Echinops Spinosus<\/jats:italic>\n                    <\/jats:italic>\n                    L. roots (ESRE), abundant in bioactive chemicals, as a natural reducing agent. The impacts of different quantities of precursors and reducing agents were methodically examined. The synthesized ZnO nanoparticles were characterized by zeta potential measurements (\u221215.2 mV), transmission electron microscopy (TEM), which indicated spherical and hexagonal morphologies with an average size of 20.47\u201348.22\u2009nm, and energy-dispersive X-ray spectroscopy (EDX), confirming zinc and oxygen as the principal elements. Fourier transform infrared spectroscopy (FTIR) underscored plant-derived compounds\u2019 contribution to nanoparticle stabilization. Cytotoxicity was assessed using the MTT assay on two cancer cell lines, HepG2 (hepatocellular carcinoma) and MCF-7 (breast cancer). The green-synthesized ZnO nanoparticles had substantial anticancer efficacy, with the ZnO nanoparticles exhibiting the most pronounced anti-proliferative effect on HepG2 cells (10.4 folds) and 5.4 folds more effective in MCF-7 cells compared to ESRE, with HepG2 cells IC50 value of 19.94\u2009\u00b1\u20090.11 \u00b5g\/mL while the IC50 for MCF-7 cells was 75.65\u2009\u00b1\u20090.16 \u00b5g\/mL. The results indicate that ZnO-NPs produced by green technologies exhibit significant potential as anticancer agents, especially for hepatocellular carcinoma treatment.\n                  <\/jats:p>","DOI":"10.1371\/journal.pone.0331171","type":"journal-article","created":{"date-parts":[[2025,10,23]],"date-time":"2025-10-23T17:38:46Z","timestamp":1761241126000},"page":"e0331171","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":8,"title":["Green-synthesized zinc oxide nanoparticles using Echinops spinosus extract: A promising anticancer agent for hepatocellular carcinoma"],"prefix":"10.1371","volume":"20","author":[{"given":"Rabab S.","family":"Hamad","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammed Ahmed Ali","family":"Elshaer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hesham A.","family":"El-Mahdy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Osama A.","family":"Mohammed","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3827-3122","authenticated-orcid":true,"given":"Mohammed","family":"Jeelani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0136-7096","authenticated-orcid":true,"given":"Ahmed S.","family":"Doghish","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamed Awad Mahmoud","family":"Abd-Elraheem","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mervat Mostafa","family":"Abdel mageed","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amira Abd-elfattah","family":"Darwish","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elwathiq Khalid","family":"Ibrahim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Walaa A.","family":"El-Dakroury","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2025,10,23]]},"reference":[{"issue":"15","key":"pone.0331171.ref001","doi-asserted-by":"crossref","first-page":"5354","DOI":"10.3390\/ma16155354","article-title":"Nanoparticles in cancer diagnosis and treatment","volume":"16","author":"J Baranwal","year":"2023","journal-title":"Materials (Basel)"},{"key":"pone.0331171.ref002","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1016\/j.bmt.2023.09.001","article-title":"Review of the efficacy of nanoparticle-based drug delivery systems for cancer treatment","volume":"5","author":"K Elumalai","year":"2024","journal-title":"Biomed Technol"},{"issue":"3","key":"pone.0331171.ref003","doi-asserted-by":"crossref","first-page":"1962","DOI":"10.1002\/jcp.29126","article-title":"Nanoparticles and cancer therapy: perspectives for application of nanoparticles in the treatment of cancers","volume":"235","author":"A Aghebati-Maleki","year":"2020","journal-title":"J Cell Physiol"},{"issue":"5","key":"pone.0331171.ref004","doi-asserted-by":"crossref","first-page":"1310","DOI":"10.1158\/1078-0432.CCR-07-1441","article-title":"Therapeutic nanoparticles for drug delivery in cancer","volume":"14","author":"K Cho","year":"2008","journal-title":"Clin Cancer Res"},{"issue":"8","key":"pone.0331171.ref005","doi-asserted-by":"crossref","first-page":"6184","DOI":"10.1021\/nn200739q","article-title":"A folate receptor-targeting nanoparticle minimizes drug resistance in a human cancer model","volume":"5","author":"X Wang","year":"2011","journal-title":"ACS Nano"},{"issue":"9","key":"pone.0331171.ref006","doi-asserted-by":"crossref","first-page":"1261","DOI":"10.1080\/17425247.2021.1912008","article-title":"Metallic nanoparticles as drug delivery system for the treatment of cancer","volume":"18","author":"N Desai","year":"2021","journal-title":"Expert Opin Drug Deliv"},{"issue":"11","key":"pone.0331171.ref007","doi-asserted-by":"crossref","first-page":"2818","DOI":"10.3390\/cancers13112818","article-title":"A systematic review of biosynthesized metallic nanoparticles as a promising anti-cancer-strategy","volume":"13","author":"A Andleeb","year":"2021","journal-title":"Cancers (Basel)"},{"issue":"27","key":"pone.0331171.ref008","doi-asserted-by":"crossref","first-page":"15357","DOI":"10.1039\/C9RA01659G","article-title":"Biogenesis of ZnO nanoparticles using Pandanus odorifer leaf extract: anticancer and antimicrobial activities","volume":"9","author":"A Hussain","year":"2019","journal-title":"RSC Adv"},{"issue":"1","key":"pone.0331171.ref009","doi-asserted-by":"crossref","first-page":"9055","DOI":"10.1038\/s41598-020-65949-3","article-title":"Green route to synthesize Zinc Oxide Nanoparticles using leaf extracts of Cassia fistula and Melia azadarach and their antibacterial potential","volume":"10","author":"M Naseer","year":"2020","journal-title":"Sci Rep"},{"key":"pone.0331171.ref010","doi-asserted-by":"crossref","first-page":"4786227","DOI":"10.1155\/2021\/4786227","article-title":"Plant-based synthesis of zinc oxide nanoparticles (ZnO-NPs) using aqueous leaf extract of Aquilegia pubiflora: their antiproliferative activity against HepG2 cells inducing reactive oxygen species and other in vitro properties","volume":"2021","author":"H Jan","year":"2021","journal-title":"Oxid Med Cell Longev"},{"issue":"2","key":"pone.0331171.ref011","doi-asserted-by":"crossref","first-page":"40","DOI":"10.5455\/jcmr.20180318051853","article-title":"Ethnopharmacognosy of Echinops spinosus L. in North Africa: a mini review","volume":"9","author":"A Bouzabata","year":"2018","journal-title":"J Complement Med Res"},{"key":"pone.0331171.ref012","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1007\/978-3-319-59135-3_3","article-title":"The coastal desert of Egypt.","volume-title":"Plant responses to hyperarid desert environments","author":"MM Abd El-Ghani","year":"2017"},{"issue":"2","key":"pone.0331171.ref013","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1139\/bcb-2018-0212","article-title":"Biological activity of Echinops spinosus on inhibition of paracetamol-induced renal inflammation","volume":"97","author":"MGA Hegazy","year":"2019","journal-title":"Biochem Cell Biol"},{"issue":"1","key":"pone.0331171.ref014","first-page":"91","article-title":"Acute toxicity, phenol content, antioxidant and postprandial anti-diabetic activity of Echinops spinosus extracts","volume":"9","author":"K Benrahou","year":"2022","journal-title":"IJSM"},{"key":"pone.0331171.ref015","doi-asserted-by":"crossref","first-page":"1234","DOI":"10.3389\/fphar.2019.01234","article-title":"The genus echinops: phytochemistry and biological activities: a review","volume":"10","author":"H Bitew","year":"2019","journal-title":"Front Pharmacol"},{"key":"pone.0331171.ref016","doi-asserted-by":"crossref","first-page":"102102","DOI":"10.1016\/j.bcab.2021.102102","article-title":"In vitro screening of phytochemicals, antioxidant, antimicrobial, and cytotoxic activity of Echinops setifer extract","volume":"35","author":"F Falah","year":"2021","journal-title":"Biocatal Agric Biotechnol"},{"issue":"1","key":"pone.0331171.ref017","first-page":"205","article-title":"An updated review of the ethnopharmacological uses, phytochemistry and selected biological activities of genus Echinops L","volume":"67","author":"MA Elseragy","year":"2024","journal-title":"Egypt J Chem"},{"issue":"5","key":"pone.0331171.ref018","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1007\/s00339-024-07440-8","article-title":"Allium hooshidaryae (Alliaceae)-based green-synthesized Fe3O4@MoS2 core\u2013shell nanoparticles coated with chitosan and investigating their biological properties","volume":"130","author":"M Abbasi","year":"2024","journal-title":"Appl Phys A"},{"issue":"3","key":"pone.0331171.ref019","doi-asserted-by":"crossref","first-page":"250","DOI":"10.1007\/s00339-022-05387-2","article-title":"Magnetic graphite-ODA@CoFe2O4: attempting to produce and characterize the development of an innovative nanocomposite to investigate its antimicrobial properties","volume":"128","author":"F Dehghani","year":"2022","journal-title":"Appl Phys A"},{"issue":"8","key":"pone.0331171.ref020","doi-asserted-by":"crossref","first-page":"696","DOI":"10.1007\/s00339-022-05763-y","article-title":"Rutin precursor for the synthesis of superparamagnetic ZnFe2O4 nanoparticles: experimental and density functional theory","volume":"128","author":"AM Amani","year":"2022","journal-title":"Appl Phys A"},{"key":"pone.0331171.ref021","doi-asserted-by":"crossref","first-page":"122781","DOI":"10.1016\/j.jnoncrysol.2023.122781","article-title":"Fabrication and characterization of novel ZnO-loaded mesoporous bioactive glass nanospheres with enhanced physiochemical properties and biocompatibility for bone tissue engineering","volume":"626","author":"AH Taghvaei","year":"2024","journal-title":"J Non-Cryst Solids"},{"key":"pone.0331171.ref022","volume-title":"Phytochemical methods: a guide to modern techniques of plant analysis","author":"J Harborne","year":"1998"},{"key":"pone.0331171.ref023","first-page":"50","article-title":"Phytochemical screening and antioxidant activity of aqueous extract of Genista saharae (Coss. & Dur.)","volume":"8","author":"S Guettaf","year":"2016","journal-title":"Der Pharmacia Lettre"},{"issue":"5","key":"pone.0331171.ref024","doi-asserted-by":"crossref","first-page":"731","DOI":"10.3390\/biom10050731","article-title":"Assessment of the pharmacological properties and phytochemical profile of Bruguiera gymnorhiza (L.) lam using in vitro studies, in silico docking, and multivariate analysis","volume":"10","author":"NB Sadeer","year":"2020","journal-title":"Biomolecules"},{"key":"pone.0331171.ref025","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1016\/j.fsi.2020.03.009","article-title":"Dual immunological and oxidative responses in Oreochromis niloticus fish exposed to lambda cyhalothrin and concurrently fed with Thyme powder (Thymus vulgaris L.): Stress and immune encoding gene expression","volume":"100","author":"SR Khalil","year":"2020","journal-title":"Fish Shellfish Immunol"},{"issue":"1","key":"pone.0331171.ref026","first-page":"11","article-title":"Antioxidant activity and HPLC screening of Pimpinella anisum","volume":"7","author":"NM El Aali","year":"2021","journal-title":"J Pharm Appl Chem"},{"key":"pone.0331171.ref027","first-page":"238","article-title":"Biogenic production of zinc oxide nanoparticles using Acalypha indica","volume":"4","author":"D Gnanasangeetha","year":"2013","journal-title":"J Chem Biol Phys Sci"},{"key":"pone.0331171.ref028","doi-asserted-by":"crossref","first-page":"632505","DOI":"10.3389\/fmicb.2021.632505","article-title":"Green synthesized silver nanoparticles: antibacterial and anticancer activities, biocompatibility, and analyses of surface-attached proteins","volume":"12","author":"M Wypij","year":"2021","journal-title":"Front Microbiol"},{"issue":"2","key":"pone.0331171.ref029","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1039\/C0NR00656D","article-title":"Extracellular biosynthesis and characterization of silver nanoparticles using Aspergillus flavus NJP08: a mechanism perspective","volume":"3","author":"N Jain","year":"2011","journal-title":"Nanoscale"},{"issue":"1","key":"pone.0331171.ref030","doi-asserted-by":"crossref","first-page":"27","DOI":"10.5941\/MYCO.2012.40.1.027","article-title":"Antimicrobial and synergistic effects of silver nanoparticles synthesized using soil fungi of high altitudes of eastern himalaya","volume":"40","author":"LS Devi","year":"2012","journal-title":"Mycobiology"},{"issue":"3","key":"pone.0331171.ref031","first-page":"035015","article-title":"ROS-dependent anticandidal activity of zinc oxide nanoparticles synthesized by using egg albumen as a biotemplate","volume":"4","author":"M Shoeb","year":"2013","journal-title":"Adv Nat Sci: Nanosci Nanotechnol"},{"issue":"5","key":"pone.0331171.ref032","doi-asserted-by":"crossref","first-page":"1075","DOI":"10.1007\/s10895-020-02578-z","article-title":"Multifunctional ZnO\/SiO2 core\/shell nanoparticles for bioimaging and drug delivery application","volume":"30","author":"APS Prasanna","year":"2020","journal-title":"J Fluoresc"},{"issue":"2","key":"pone.0331171.ref033","doi-asserted-by":"crossref","first-page":"364","DOI":"10.3390\/en11020364","article-title":"Fourier transform infrared (FTIR) spectroscopy analysis of transformer paper in mineral oil-paper composite insulation under accelerated thermal aging","volume":"11","author":"A Munajad","year":"2018","journal-title":"Energies"},{"key":"pone.0331171.ref034","first-page":"104040","article-title":"Design, optimization, and in-vivo performance of glipizide-loaded O-carboxymethyl chitosan nanoparticles in insulin resistant\/type 2 diabetic rat model","volume":"79","author":"WA El-Dakroury","year":"2023","journal-title":"JDDST"},{"key":"pone.0331171.ref035","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/0022-1759(83)90303-4","article-title":"Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays","volume":"65","author":"T Mosmann","year":"1983","journal-title":"J Immunol Methods"},{"issue":"1","key":"pone.0331171.ref036","first-page":"66","article-title":"Solvent effects on phenolic contents and antioxidant activities of the Echinops spinosus and the Limoniastrum monopetalum","volume":"5","author":"O Khedher","year":"2014","journal-title":"Res J Pharm Biol Chem Sci"},{"issue":"2","key":"pone.0331171.ref037","doi-asserted-by":"crossref","first-page":"886","DOI":"10.1007\/s10904-020-01729-w","article-title":"Green synthesis of biogenic zinc oxide nanoflower as dual agent for photodegradation of an organic dye and tyrosinase inhibitor","volume":"31","author":"AC Ekennia","year":"2020","journal-title":"J Inorg Organomet Polym"},{"issue":"4","key":"pone.0331171.ref038","doi-asserted-by":"crossref","first-page":"59","DOI":"10.3390\/ph13040059","article-title":"In vitro antibacterial and antiproliferative potential of Echinops lanceolatus Mattf. (Asteraceae) and identification of potential bioactive compounds","volume":"13","author":"A Jackson Seukep","year":"2020","journal-title":"Pharmaceuticals (Basel)"},{"issue":"20","key":"pone.0331171.ref039","doi-asserted-by":"crossref","first-page":"13105","DOI":"10.1021\/acsomega.1c00837","article-title":"Echinops taeckholmiana Amin: optimization of a tissue culture protocol, biological evaluation, and chemical profiling using GC and LC-MS","volume":"6","author":"DI Hamdan","year":"2021","journal-title":"ACS Omega"},{"key":"pone.0331171.ref040","doi-asserted-by":"crossref","first-page":"820","DOI":"10.1016\/j.jff.2015.06.018","article-title":"Phenolics and polyphenolics in foods, beverages and spices: antioxidant activity and health effects \u2013 a review","volume":"18","author":"F Shahidi","year":"2015","journal-title":"J Funct Foods"},{"key":"pone.0331171.ref041","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1007\/978-981-13-3810-6_8","article-title":"Polyphenols as natural antioxidants: Sources, extraction and applications in food, cosmetics and drugs.","volume-title":"Plant based \u201cGreen Chemistry 2.0\u201d moving from evolutionary to revolutionary","author":"MK Khan","year":"2019"},{"issue":"1","key":"pone.0331171.ref042","doi-asserted-by":"crossref","first-page":"40","DOI":"10.3390\/compounds3010005","article-title":"Polyphenols in health and disease: gut microbiota, bioaccessibility, and bioavailability","volume":"3","author":"J Bi\u00e9","year":"2023","journal-title":"Compounds"},{"issue":"3","key":"pone.0331171.ref043","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1016\/j.freeradbiomed.2004.04.034","article-title":"Potential toxicity of flavonoids and other dietary phenolics: significance for their chemopreventive and anticancer properties","volume":"37","author":"G Galati","year":"2004","journal-title":"Free Radic Biol Med"},{"issue":"3","key":"pone.0331171.ref044","doi-asserted-by":"crossref","first-page":"591","DOI":"10.3390\/antiox11030591","article-title":"Combinatorial effects of the natural products arctigenin, chlorogenic acid, and cinnamaldehyde commit oxidation assassination on breast cancer cells","volume":"11","author":"C Schuster","year":"2022","journal-title":"Antioxidants (Basel)"},{"issue":"9","key":"pone.0331171.ref045","first-page":"2821","article-title":"Gallic acid induces G\u2080\/G\u2081 phase arrest and apoptosis in human leukemia HL-60 cells through inhibiting cyclin D and E, and activating mitochondria-dependent pathway","volume":"31","author":"R-D Yeh","year":"2011","journal-title":"Anticancer Res"},{"issue":"2","key":"pone.0331171.ref046","first-page":"377","article-title":"Gallic acid induces apoptosis in A375.S2 human melanoma cells through caspase-dependent and -independent pathways","volume":"37","author":"C Lo","year":"2010","journal-title":"Int J Oncol"},{"issue":"20","key":"pone.0331171.ref047","doi-asserted-by":"crossref","first-page":"84","DOI":"10.4103\/0973-7847.194044","article-title":"Overviews of biological importance of quercetin: a bioactive flavonoid","volume":"10","author":"AV Anand David","year":"2016","journal-title":"Pharmacogn Rev"},{"key":"pone.0331171.ref048","doi-asserted-by":"crossref","first-page":"541","DOI":"10.3389\/fonc.2019.00541","article-title":"Chemical and pharmacological aspects of caffeic acid and its activity in hepatocarcinoma","volume":"9","author":"KMM Esp\u00edndola","year":"2019","journal-title":"Front Oncol"},{"issue":"19","key":"pone.0331171.ref049","doi-asserted-by":"crossref","first-page":"6085","DOI":"10.1016\/j.bmcl.2012.08.038","article-title":"Biological activity evaluation and structure-activity relationships analysis of ferulic acid and caffeic acid derivatives for anticancer","volume":"22","author":"W Li","year":"2012","journal-title":"Bioorg Med Chem Lett"},{"key":"pone.0331171.ref050","doi-asserted-by":"crossref","unstructured":"Muhammad Younus MY, Khan F, Sabira Sultana SS, Asif H. Spectral analysis and antibacterial activity of methanol extract of roots of Echinops echinatus and its fractions. 2016.","DOI":"10.4172\/1948-5948.1000288"},{"issue":"24","key":"pone.0331171.ref051","first-page":"3440","article-title":"Echinops spinosissimus turra root methanolic extract: characterization of the bioactive components and relative wound healing, antimicrobial and antioxidant properties","volume":"11","author":"SH Zitouni-Nourine","year":"2022","journal-title":"Plants (Basel)"},{"issue":"24","key":"pone.0331171.ref052","doi-asserted-by":"crossref","first-page":"5786","DOI":"10.1080\/14786419.2020.1837812","article-title":"Phenolic profile (HPLC-UV) analysis and biological activities of two organic extracts from Echinops spinosissimus Turra roots growing in Tunisia","volume":"35","author":"O Khedher","year":"2021","journal-title":"Nat Prod Res"},{"issue":"3","key":"pone.0331171.ref053","doi-asserted-by":"crossref","first-page":"453","DOI":"10.3390\/antiox11030453","article-title":"HR-LC-ESI-Orbitrap-MS-Based metabolic profiling coupled with chemometrics for the discrimination of different echinops spinosus organs and evaluation of their antioxidant activity","volume":"11","author":"A Bouzabata","year":"2022","journal-title":"Antioxidants (Basel)"},{"issue":"19","key":"pone.0331171.ref054","doi-asserted-by":"crossref","first-page":"3456","DOI":"10.3390\/nano12193456","article-title":"A review of the green synthesis of ZnO nanoparticles utilising southern african indigenous medicinal plants","volume":"12","author":"D Mutukwa","year":"2022","journal-title":"Nanomaterials (Basel)"},{"issue":"2","key":"pone.0331171.ref055","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1007\/s40097-021-00460-3","article-title":"Comparative evaluation of chemically and green synthesized zinc oxide nanoparticles: their in vitro antioxidant, antimicrobial, cytotoxic and anticancer potential towards HepG2 cell line","volume":"13","author":"H Ashraf","year":"2022","journal-title":"J Nanostruct Chem"},{"issue":"11","key":"pone.0331171.ref056","first-page":"2447","article-title":"Nano zinc oxide green-synthesized from Plumbago auriculata lam. alcoholic extract","volume":"10","author":"MM Melk","year":"2021","journal-title":"Plants (Basel)"},{"issue":"4","key":"pone.0331171.ref057","doi-asserted-by":"crossref","first-page":"675","DOI":"10.1007\/s13204-018-0698-8","article-title":"Structural characterization of mesoporous magnetite nanoparticles synthesized using the leaf extract of Calliandra haematocephala and their photocatalytic degradation of malachite green dye","volume":"8","author":"KD Sirdeshpande","year":"2018","journal-title":"Appl Nanosci"},{"key":"pone.0331171.ref058","doi-asserted-by":"crossref","first-page":"101129","DOI":"10.1016\/j.bcab.2019.101129","article-title":"Hydnocarpus alpina Wt extract mediated green synthesis of ZnO nanoparticle and screening of its anti-microbial, free radical scavenging, and photocatalytic activity","volume":"19","author":"M Ganesh","year":"2019","journal-title":"Biocatal Agric Biotechnol"},{"key":"pone.0331171.ref059","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1016\/j.jphotobiol.2019.04.001","article-title":"Cucurbita pepo leaf extract induced synthesis of zinc oxide nanoparticles, characterization for the treatment of femoral fracture","volume":"195","author":"D Hu","year":"2019","journal-title":"J Photochem Photobiol B"},{"key":"pone.0331171.ref060","first-page":"100995","article-title":"Green synthesis and characterization of zinc oxide nanoparticles using Cayratia pedata leaf extract","volume":"26","author":"A Jayachandran","year":"2021","journal-title":"Biochem Biophys Rep"},{"issue":"12","key":"pone.0331171.ref061","doi-asserted-by":"crossref","first-page":"4033","DOI":"10.1039\/c3ra22959a","article-title":"Green synthesis of nano platinum using naturally occurring polyphenols","volume":"3","author":"KM Kumar","year":"2013","journal-title":"RSC Adv"},{"key":"pone.0331171.ref062","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1007\/978-1-60327-198-1_6","article-title":"Zeta potential measurement.","volume-title":"Characterization of nanoparticles intended for drug delivery","author":"JD Clogston","year":"2011"},{"issue":"1","key":"pone.0331171.ref063","first-page":"14","article-title":"Green synthesis of ZnO nanoparticles from Foeniculum vulgare Mill. seed extract and its antibacterial effects on foodborne bacteria","volume":"22","author":"P Salari","year":"2023","journal-title":"J Med Plants"},{"key":"pone.0331171.ref064","first-page":"1","article-title":"Removal of paracetamol from aqueous solution with zinc oxide nanoparticles obtained by green synthesis from purple basil (Ocimum basilicum L.) waste","author":"A Solmaz","year":"2024","journal-title":"Biomass Convers Biorefin"},{"issue":"31","key":"pone.0331171.ref065","doi-asserted-by":"crossref","first-page":"4600","DOI":"10.1016\/j.biomaterials.2007.07.029","article-title":"Protein adsorption and cellular uptake of cerium oxide nanoparticles as a function of zeta potential","volume":"28","author":"S Patil","year":"2007","journal-title":"Biomaterials"},{"issue":"14","key":"pone.0331171.ref066","doi-asserted-by":"crossref","first-page":"9709","DOI":"10.1021\/acsomega.1c00310","article-title":"Green synthesis of zinc oxide (ZnO) nanoparticles using aqueous fruit extracts of myristica fragrans: their characterizations and biological and environmental applications","volume":"6","author":"S Faisal","year":"2021","journal-title":"ACS Omega"},{"issue":"9","key":"pone.0331171.ref067","doi-asserted-by":"crossref","first-page":"4409","DOI":"10.1039\/D3NJ00131H","article-title":"Eco-friendly synthesis of ZnO-nanoparticles using Phoenix dactylifera L., polyphenols: physicochemical, microstructural, and functional assessment","volume":"47","author":"JAA Abdullah","year":"2023","journal-title":"New J Chem"},{"issue":"1","key":"pone.0331171.ref068","doi-asserted-by":"crossref","first-page":"13470","DOI":"10.1038\/s41598-024-63258-7","article-title":"Green synthesis of zinc oxide nanoparticles using Rhus coriaria extract and their anticancer activity against triple-negative breast cancer cells","volume":"14","author":"Y Mongy","year":"2024","journal-title":"Sci Rep"},{"issue":"9","key":"pone.0331171.ref069","doi-asserted-by":"crossref","DOI":"10.1016\/j.heliyon.2020.e04896","article-title":"Optimization of green biosynthesized visible light active CuO\/ZnO nano-photocatalysts for the degradation of organic methylene blue dye","volume":"6","author":"A Fouda","year":"2020","journal-title":"Heliyon"},{"issue":"19","key":"pone.0331171.ref070","doi-asserted-by":"crossref","first-page":"4521","DOI":"10.3390\/molecules25194521","article-title":"Green synthesis of zinc oxide nanoparticles from pomegranate (Punica granatum) extracts and characterization of their antibacterial activity","volume":"25","author":"UL Ifeanyichukwu","year":"2020","journal-title":"Molecules"},{"key":"pone.0331171.ref071","doi-asserted-by":"crossref","first-page":"643","DOI":"10.1016\/j.sajb.2024.02.049","article-title":"Green-route synthesis of ZnO nanoparticles via Solanum surattense leaf extract: characterization, biomedical applications and their ecotoxicity assessment of zebrafish embryo model","volume":"167","author":"C Ragavendran","year":"2024","journal-title":"S Afr J Bot"},{"issue":"1","key":"pone.0331171.ref072","first-page":"1","article-title":"Green synthesis of zinc oxide nanoparticles using Punica granatum leaf extract and its application towards photocatalytic degradation of Coomassie brilliant blue R-250 dye","volume":"1","author":"K Singh","year":"2019","journal-title":"SN Appl Sci"},{"issue":"5","key":"pone.0331171.ref073","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s00339-016-0069-9","article-title":"Bio-inspired ZnO nanoparticles from Ocimum tenuiflorum and their in vitro antioxidant activity","volume":"122","author":"NJ Sushma","year":"2016","journal-title":"Appl Phys A"},{"key":"pone.0331171.ref074","doi-asserted-by":"crossref","first-page":"118518","DOI":"10.1016\/j.lfs.2020.118518","article-title":"Diltiazem potentiates the cytotoxicity of gemcitabine and 5-fluorouracil in PANC-1 human pancreatic cancer cells through inhibition of P-glycoprotein","volume":"262","author":"HA El-Mahdy","year":"2020","journal-title":"Life Sci"},{"issue":"1","key":"pone.0331171.ref075","doi-asserted-by":"crossref","first-page":"380","DOI":"10.1080\/14756366.2021.2015342","article-title":"1,3,4-Oxadiazole-naphthalene hybrids as potential VEGFR-2 inhibitors: design, synthesis, antiproliferative activity, apoptotic effect, and in silico studies","volume":"37","author":"M Hagras","year":"2022","journal-title":"J Enzyme Inhib Med Chem"},{"issue":"1","key":"pone.0331171.ref076","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1080\/14756366.2021.2015343","article-title":"New benzoxazole derivatives as potential VEGFR-2 inhibitors and apoptosis inducers: design, synthesis, anti-proliferative evaluation, flowcytometric analysis, and in silico studies","volume":"37","author":"H Elkady","year":"2022","journal-title":"J Enzyme Inhib Med Chem"},{"key":"pone.0331171.ref077","doi-asserted-by":"crossref","first-page":"136336","DOI":"10.1016\/j.molstruc.2023.136336","article-title":"New theobromine derivative as apoptotic anti-triple-negative breast cancer targeting EGFR protein: CADD story","volume":"1294","author":"IH Eissa","year":"2023","journal-title":"J Mol Struct"},{"issue":"19","key":"pone.0331171.ref078","doi-asserted-by":"crossref","first-page":"6910","DOI":"10.3390\/molecules28196910","article-title":"Thymus vulgaris oil nanoemulsion: synthesis, characterization, antimicrobial and anticancer activities","volume":"28","author":"AS Doghish","year":"2023","journal-title":"Molecules"},{"key":"pone.0331171.ref079","first-page":"149","article-title":"Differential susceptibility of Caco-2 and HepG2 human cell lines to oxidative stress","author":"KR Martin","year":"1997","journal-title":"J Elisha Mitchell Sci Soc"},{"issue":"3","key":"pone.0331171.ref080","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1080\/02772248.2013.789606","article-title":"Effect of Zinc Oxide nanoparticles on cellular oxidative stress and antioxidant defense mechanisms in mouse liver","volume":"95","author":"S Syama","year":"2013","journal-title":"Toxicol Environ Chem"},{"issue":"2019","key":"pone.0331171.ref081","doi-asserted-by":"crossref","first-page":"909","DOI":"10.3390\/ma12060909","article-title":"Nanocomplexes of graphene oxide and platinum nanoparticles against colorectal cancer Colo205, HT-29, HTC-116, SW480, liver cancer HepG2, human breast cancer MCF-7, and adenocarcinoma LNCaP and human cervical Hela B cell lines","volume":"12","author":"M Kutwin","year":"2019","journal-title":"Materials"},{"issue":"1","key":"pone.0331171.ref082","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1186\/s12645-018-0037-5","article-title":"Antiangiogenic and antiapoptotic effects of green-synthesized zinc oxide nanoparticles using Sargassum muticum algae extraction","volume":"9","author":"Z Sanaeimehr","year":"2018","journal-title":"Cancer Nanotechnol"},{"key":"pone.0331171.ref083","doi-asserted-by":"crossref","first-page":"8817110","DOI":"10.1155\/2020\/8817110","article-title":"Synthesis and characterization of green zinc oxide nanoparticles with antiproliferative effects through apoptosis induction and microRNA modulation in breast cancer cells","volume":"2020","author":"AH Aalami","year":"2020","journal-title":"Bioinorg Chem Appl"},{"issue":"1","key":"pone.0331171.ref084","doi-asserted-by":"crossref","first-page":"2419806","DOI":"10.1080\/20565623.2024.2419806","article-title":"Green synthesized Zingiber officinale-ZnO nanoparticles: anticancer efficacy against 3D breast cancer model","volume":"10","author":"R Alhaddad","year":"2024","journal-title":"Future Sci OA"},{"key":"pone.0331171.ref085","doi-asserted-by":"crossref","first-page":"1747","DOI":"10.1007\/s13204-021-01837-0","article-title":"Green synthesis of zinc oxide nanoparticles using the root hair extract of Phoenix dactylifera: antimicrobial and anticancer activity","volume":"11","author":"R Naser","year":"2021","journal-title":"Appl Nanosci"},{"issue":"6","key":"pone.0331171.ref086","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1166\/asem.2018.2190","article-title":"Green synthesis of nanoparticles and their applications","volume":"10","author":"A Dashora","year":"2018","journal-title":"Adv Sci Eng Med"},{"issue":"2","key":"pone.0331171.ref087","first-page":"113","article-title":"Cytotoxic activity of zinc oxide\/titanium dioxide nanoparticles on prostate cancer cells","volume":"3","author":"A Tas","year":"2019","journal-title":"IJCT"},{"key":"pone.0331171.ref088","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1186\/1477-3155-11-26","article-title":"Interaction of nanoparticles with proteins: relation to bio-reactivity of the nanoparticle","volume":"11","author":"SR Saptarshi","year":"2013","journal-title":"J Nanobiotechnology"},{"issue":"9","key":"pone.0331171.ref089","doi-asserted-by":"crossref","first-page":"1063","DOI":"10.1517\/17425247.2010.502560","article-title":"Zinc oxide nanoparticles for selective destruction of tumor cells and potential for drug delivery applications","volume":"7","author":"JW Rasmussen","year":"2010","journal-title":"Expert Opin Drug Deliv"},{"issue":"8","key":"pone.0331171.ref090","doi-asserted-by":"crossref","first-page":"6422","DOI":"10.1021\/nn4037927","article-title":"A multi-stakeholder perspective on the use of alternative test strategies for nanomaterial safety assessment","volume":"7","author":"AE Nel","year":"2013","journal-title":"ACS Nano"},{"key":"pone.0331171.ref091","doi-asserted-by":"crossref","first-page":"12889","DOI":"10.2147\/IJN.S487188","article-title":"Green synthesis of zinc oxide nanoparticles: preparation, characterization, and biomedical applications - a review","volume":"19","author":"MT El-Saadony","year":"2024","journal-title":"Int J Nanomedicine"},{"issue":"2","key":"pone.0331171.ref092","doi-asserted-by":"crossref","first-page":"1914","DOI":"10.1021\/acsomega.1c05324","article-title":"Non-antimicrobial and non-anticancer properties of ZnO nanoparticles biosynthesized using different plant parts of Bixa orellana","volume":"7","author":"S Gharpure","year":"2022","journal-title":"ACS Omega"}],"container-title":["PLOS One"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0331171","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,23]],"date-time":"2025-10-23T17:38:59Z","timestamp":1761241139000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0331171"}},"subtitle":[],"editor":[{"given":"Huzaifa","family":"Umar","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2025,10,23]]},"references-count":92,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2025,10,23]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0331171","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10,23]]}}}