{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T03:01:31Z","timestamp":1787022091129,"version":"build-2736575974"},"reference-count":87,"publisher":"Public Library of Science (PLoS)","issue":"10","license":[{"start":{"date-parts":[[2021,10,1]],"date-time":"2021-10-01T00:00:00Z","timestamp":1633046400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:sec id=\"sec001\">\n                    <jats:title>Purpose<\/jats:title>\n                    <jats:p>\n                      This study aims to prepare folic acid coated tin oxide nanoparticles (FA-SnO\n                      <jats:sub>2<\/jats:sub>\n                      NPs) for specifically targeting human ovarian cancer cells with minimum side effects against normal cells.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec002\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      The prepared FA-SnO\n                      <jats:sub>2<\/jats:sub>\n                      NPs were characterized by FT-IR, UV-vis spectroscopy, XRD, SEM and TEM. The inhibition effects of FA-SnO\n                      <jats:sub>2<\/jats:sub>\n                      NPs against SKOV3 cancer cell were tested by MTT and LDH assay. Apoptosis induction in FA-SnO\n                      <jats:sub>2<\/jats:sub>\n                      NPs treated SKOV3 cells were investigated using Annexin V\/PI, AO\/EB and Comet assays and the possible mechanisms of the cytotoxic action were studied by Flow cytometry, qRT-PCR, Immunohistochemistry, and Western blotting analyses. The effects of FA-SnO\n                      <jats:sub>2<\/jats:sub>\n                      NPs on reactive oxygen species generation in SKOV3 cells were also examined. Additionally, the safety of utilization FA-SnO\n                      <jats:sub>2<\/jats:sub>\n                      NPs were studied in vivo using Wister rats.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec003\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The obtained FA-SnO\n                      <jats:sub>2<\/jats:sub>\n                      NPs displayed amorphous spherical morphology with an average diameter of 157 nm and a zeta potential value of -24 mV. Comparing to uncoated SnO\n                      <jats:sub>2<\/jats:sub>\n                      NPs, FA-SnO\n                      <jats:sub>2<\/jats:sub>\n                      NPs had a superior inhibition effect towards SKOV3 cell growth that was suggested to be mediated through higher reactive oxygen species generation. It was showed that FA-SnO\n                      <jats:sub>2<\/jats:sub>\n                      NPs increased significantly the % of apoptotic cells in the sub- G1 and G2\/M phases with a higher intensity comet nucleus in SKOV3 treated cells. Furthermore, FA-SnO\n                      <jats:sub>2<\/jats:sub>\n                      NPs was significantly increased the expression levels of P53, Bax, and cleaved Caspase-3 and accompanied with a significant decrease of Bcl-2 in the treated SKOV3 cells.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec004\">\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      Overall, the results suggested that an increase in cellular FA-SnO\n                      <jats:sub>2<\/jats:sub>\n                      NPs internalization resulted in a significant induced cytotoxicity in SKOV3 cancer cells in dose-dependent mode through ROS-mediated cell apoptosis that may have occurred through mitochondrial pathway. Additionally, the results confirmed the safety of utilization FA-SnO\n                      <jats:sub>2<\/jats:sub>\n                      NPs against living systems. So, FA-SnO\n                      <jats:sub>2<\/jats:sub>\n                      NPs with a specific targeting moiety may be a promising therapeutic candidate for human ovarian cancer.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1371\/journal.pone.0258115","type":"journal-article","created":{"date-parts":[[2021,10,1]],"date-time":"2021-10-01T15:22:08Z","timestamp":1633101728000},"page":"e0258115","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":27,"title":["Induction of mitochondria mediated apoptosis in human ovarian cancer cells by folic acid coated tin oxide nanoparticles"],"prefix":"10.1371","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8334-7330","authenticated-orcid":true,"given":"Demiana H.","family":"Hanna","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gamal","family":"R. 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Ultrasound CT and MRI."},{"key":"pone.0258115.ref002","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1186\/s12885-016-2206-4","article-title":"Folic acid tagged nanoceria as a novel therapeutic agent in ovarian cancer","volume":"16","author":"M Hijaz","year":"2016","journal-title":"BMC Cancer"},{"key":"pone.0258115.ref003","doi-asserted-by":"crossref","first-page":"20724","DOI":"10.1039\/D0RA03719B","article-title":"Nanocurcumin: Preparation, characterization and cytotoxic effects towards human laryngeal cancer cells","volume":"10","author":"DH Hanna","year":"2020","journal-title":"RSC Adv"},{"key":"pone.0258115.ref004","doi-asserted-by":"crossref","first-page":"927","DOI":"10.1517\/17425247.2010.498473","article-title":"Metallic nanoparticles: technology overview and drug delivery applications in oncology","volume":"7","author":"MZ Ahmad","year":"2010","journal-title":"Expert Opinion on Drug Delivery"},{"key":"pone.0258115.ref005","doi-asserted-by":"crossref","first-page":"581","DOI":"10.1016\/j.ajps.2019.04.005","article-title":"Cancer nanotechnology: enhancing tumor cell response to chemotherapy for hepatocellular carcinoma therapy","volume":"14","author":"Y Sun","year":"2019","journal-title":"Asian J. Pharm. Sci"},{"key":"pone.0258115.ref006","doi-asserted-by":"crossref","first-page":"1300","DOI":"10.1021\/acs.molpharmaceut.9b01318","article-title":"Synergistic platinum(II) prodrug nanoparticles for enhanced breast cancer therapy","volume":"17","author":"CX Yang","year":"2020","journal-title":"Mol. Pharm"},{"key":"pone.0258115.ref007","doi-asserted-by":"crossref","first-page":"4218","DOI":"10.1039\/C6CS00636A","article-title":"Cellular uptake of nanoparticles: journey inside the cell","volume":"46","author":"S Behzadi","year":"2017","journal-title":"Chem. Soc. Rev"},{"issue":"11","key":"pone.0258115.ref008","doi-asserted-by":"crossref","first-page":"e0188639","DOI":"10.1371\/journal.pone.0188639","article-title":"Cytotoxic effect of albumin coated copper nanoparticle on human breast cancer cells of MDA-MB 231","volume":"12","author":"M Azizi","year":"2017","journal-title":"PLoS One"},{"key":"pone.0258115.ref009","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1038\/nrc3180","article-title":"Treating metastatic cancer with nanotechnology","volume":"12","author":"A Schroeder","year":"2012","journal-title":"Nat. Rev. Cancer"},{"key":"pone.0258115.ref010","doi-asserted-by":"crossref","first-page":"1825","DOI":"10.1016\/j.drudis.2017.08.006","article-title":"Zinc oxide nanoparticles: a promising nanomaterial for biomedical applications","volume":"22","author":"PK Mishra","year":"2017","journal-title":"Drug Discovery Today"},{"key":"pone.0258115.ref011","doi-asserted-by":"crossref","first-page":"12613","DOI":"10.1038\/s41598-019-48959-8","article-title":"Copper oxide nanoparticles inhibit pancreatic tumor growth primarily by targeting tumor initiating cells","volume":"9","author":"M Benguigui","year":"2019","journal-title":"Sci. Rep"},{"key":"pone.0258115.ref012","doi-asserted-by":"crossref","first-page":"8655","DOI":"10.1021\/acsnano.5b03184","article-title":"Physical Principles of Nanoparticle Cellular Endocytosis","volume":"9","author":"S Zhang","year":"2015","journal-title":"ACS Nano"},{"key":"pone.0258115.ref013","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1016\/j.ab.2004.12.026","article-title":"Folate receptor expression in carcinomas and normal tissues determined by a quantitative radioligand binding assay","volume":"338","author":"N Parker","year":"2005","journal-title":"Anal Biochem"},{"key":"pone.0258115.ref014","doi-asserted-by":"crossref","first-page":"2432","DOI":"10.1002\/1097-0142(19940501)73:9<2432::AID-CNCR2820730929>3.0.CO;2-S","article-title":"Differential regulation of folate receptor isoforms in normal and malignant tissues in vivo and in established cell lines. Physiologic and clinical implications","volume":"73","author":"JF Ross","year":"1994","journal-title":"Cancer"},{"key":"pone.0258115.ref015","doi-asserted-by":"crossref","first-page":"1181","DOI":"10.1016\/j.msec.2017.03.027","article-title":"Folic acid-tagged titanium dioxide nanoparticles for enhanced anticancer effect in osteosarcoma cells","volume":"76","author":"JW Ai","year":"2017","journal-title":"Mater. Sci. Eng. C"},{"key":"pone.0258115.ref016","doi-asserted-by":"crossref","first-page":"1553","DOI":"10.1016\/S0142-9612(01)00267-8","article-title":"Surface modification of superparamagnetic magnetite nanoparticles and their intracellular uptake","volume":"23","author":"Y Zhang","year":"2002","journal-title":"Biomaterials"},{"key":"pone.0258115.ref017","doi-asserted-by":"crossref","first-page":"48","DOI":"10.3109\/10717540903508979","article-title":"Preparation of folate-modified pullulan acetate nanoparticles for tumor-targeted drug delivery","author":"HZ Zhang","year":"2010","journal-title":"Drug Deliv"},{"key":"pone.0258115.ref018","doi-asserted-by":"crossref","first-page":"4860","DOI":"10.1016\/j.biomaterials.2013.03.029","article-title":"Targeting CCL21-folic acid-upconversion nanoparticles conjugates to folate receptor-an expressing tumor cells in an endothelial-tumor cell bilayer model","volume":"34","author":"KY Lee","year":"2013","journal-title":"Biomaterials"},{"key":"pone.0258115.ref019","doi-asserted-by":"crossref","first-page":"8382","DOI":"10.1016\/j.biomaterials.2013.07.070","article-title":"Polyethyleneimine-mediated synthesis of folic acid-targeted iron oxide nanoparticles for in vivo tumor MR imaging","volume":"34","author":"J Li","year":"2013","journal-title":"Biomaterials"},{"key":"pone.0258115.ref020","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1002\/jccs.201000034","article-title":"Synthesis and Characterization of High Surface Area Tin Oxide Nanoparticles via the Sol-Gel Method as a Catalyst for the Hydrogenation of Styrene","volume":"57","author":"R Adnan","year":"2010","journal-title":"Chinese Chemical Society Taipei"},{"key":"pone.0258115.ref021","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1016\/j.snb.2013.12.119","article-title":"One-pot synthesis and improved sensing properties of hierarchical flowerlike SnO2 assembled from sheet and ultra-thin rod subunits","volume":"194","author":"H Chen","year":"2014","journal-title":"Sens. Actuat. B Chem"},{"key":"pone.0258115.ref022","doi-asserted-by":"crossref","first-page":"372","DOI":"10.1016\/j.saa.2014.06.131","article-title":"Biogenic synthesis of SnO2 nanoparticles: evaluation of antibacterial and antioxidant activities","volume":"134","author":"V Vidhu","year":"2015","journal-title":"Spectroch. Acta Part A. Mol. Biomol. Spectrosc"},{"key":"pone.0258115.ref023","doi-asserted-by":"crossref","first-page":"768","DOI":"10.3389\/fbioe.2020.00768","article-title":"Stannic Oxide Nanoparticle Regulates Proliferation, Invasion, Apoptosis, and Oxidative Stress of Oral Cancer Cells","volume":"8","author":"H Li","year":"2020","journal-title":"Front. Bioeng. Biotechnol"},{"key":"pone.0258115.ref024","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1016\/j.jphotobiol.2016.11.017","article-title":"Cytotoxicity study of Piper nigrum seed mediated synthesized SnO2 nanoparticles towards colorectal (HCT116) and lung cancer (A549) cell lines","volume":"166","author":"SK Tammina","year":"2017","journal-title":"J. Photochem. Photobiol. B Biol"},{"key":"pone.0258115.ref025","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1016\/j.colsurfb.2018.08.040","article-title":"Oxidative stress mediated cytotoxicity of tin (IV) oxide (SnO2) nanoparticles in human breast cancer (MCF-7) cells","volume":"172","author":"M Ahamed","year":"2018","journal-title":"Coll. Surf. B Biointerf"},{"key":"pone.0258115.ref026","doi-asserted-by":"crossref","first-page":"1567","DOI":"10.1007\/s12010-014-1381-5","article-title":"Biogenic-production of SnO2 nanoparticles and its cytotoxic effect against hepatocellular carcinoma cell line (HepG2)","volume":"175","author":"SM Roopan","year":"2015","journal-title":"Appl. Biochem. Biotechnol"},{"key":"pone.0258115.ref027","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1155\/2011\/253529","article-title":"Generation of reactive oxygen species during apoptosis induced by DNA-damaging agents and\/or histone deacetylase inhibitors","volume":"2011","author":"B Brodska","year":"2011","journal-title":"Oxidative medicine and cellular longevity"},{"key":"pone.0258115.ref028","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1049\/iet-nbt.2019.0075","article-title":"Induction of extrinsic and intrinsic apoptosis in cervical cancer cells by Momordica dioica mediated gold nanoparticles","volume":"14","author":"LS Naik","year":"2020","journal-title":"IET Nanobiotechnoly"},{"key":"pone.0258115.ref029","doi-asserted-by":"crossref","first-page":"488","DOI":"10.1016\/j.coi.2007.05.004","article-title":"Bcl-2-regulated apoptosis: mechanism and therapeutic potential","volume":"19","author":"JM Adams","year":"2007","journal-title":"Curr. Opin. Immunol"},{"key":"pone.0258115.ref030","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1016\/S1097-2765(03)00050-9","article-title":"p53 has a direct apoptogenic role at the mitochondria","volume":"11","author":"M Mihara","year":"2003","journal-title":"Mol Cell"},{"key":"pone.0258115.ref031","doi-asserted-by":"crossref","first-page":"725","DOI":"10.1016\/j.molcel.2004.11.002","article-title":"DNA damage-induced downregulation of Cdc25C is mediated by p53 via two independent mechanisms: one involves direct binding to the cdc25","volume":"16","author":"S St Clair","year":"2004","journal-title":"C promoter. Mol Cell"},{"key":"pone.0258115.ref032","first-page":"6234","article-title":"Tumor susceptibility of p21(Waf1\/Cip1)-deficient mice","volume":"61","author":"J Martin-Caballero","year":"2001","journal-title":"Cancer Res"},{"key":"pone.0258115.ref033","first-page":"1","article-title":"Synthesis and characterization of tin oxide nanoparticles via sol-gel methods using ethanol as solvent","volume":"2","author":"V Singh","year":"2013","journal-title":"International Journal Of Advance Research In Science And Engineering"},{"key":"pone.0258115.ref034","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1111\/j.1582-4934.2009.00954.x","article-title":"Metformin attenuates ovarian cancer cell growth in an AMP-kinase dispensable manner","volume":"15","author":"R Rattan","year":"2011","journal-title":"J. Cell Mol. Med"},{"key":"pone.0258115.ref035","doi-asserted-by":"crossref","first-page":"3","DOI":"10.3390\/biomedicines4010003","article-title":"In vitro synergistic enhancement of Newcastle Disease Virus to 5-fluorouracil cytotoxicity against tumor cells","volume":"4","author":"AM Al-Shammari","year":"2016","journal-title":"Biomedicines"},{"key":"pone.0258115.ref036","first-page":"25","article-title":"Anticancerous and antiproliferative\/cytotoxic activity of curcuma pseudomontana (hill turmeric) collected from the sub Himalayan region of Uttrakhand, India","volume":"4","author":"VS Bisht","year":"2014","journal-title":"Asian Journal of Plant Science and Research"},{"key":"pone.0258115.ref037","doi-asserted-by":"crossref","first-page":"3945","DOI":"10.3892\/mmr.2016.4989","article-title":"Effect of recombinant human erythropoietin and doxorubicin in combination on the proliferation of MCF-7 and MDA-MB231 breast cancer cells","volume":"13","author":"M Radwan","year":"2016","journal-title":"Mol. Med. Rep"},{"key":"pone.0258115.ref038","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/0022-1759(95)00072-I","article-title":"A novel assay for apoptosis Flow cytometric detection of phosphatidylserine expression on early apoptotic cells using fluorescein labelled Annexin V","volume":"184","author":"I Vermes","year":"1995","journal-title":"J. Immunol. Methods"},{"key":"pone.0258115.ref039","doi-asserted-by":"crossref","first-page":"2323","DOI":"10.1039\/C7RA12297G","article-title":"Preparation of curcuminoid microemulsions from Curcuma longa L. to enhance inhibition effects on growth of colon cancer cells HT-29","volume":"8","author":"YC Chen","year":"2018","journal-title":"RSC Adv"},{"key":"pone.0258115.ref040","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1186\/1472-6750-5-12","article-title":"A simple technique for quantifying apoptosis in 96-well plates","volume":"5","author":"D Ribble","year":"2005","journal-title":"BMC Biotechnol"},{"key":"pone.0258115.ref041","first-page":"93","article-title":"Cellular responses induced by silver nanoparticles: In vitro studies","volume":"179","author":"S Arora","year":"2008","journal-title":"Toxicol. Appl. Pharmacol"},{"key":"pone.0258115.ref042","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1016\/0014-4827(88)90265-0","article-title":"E. Schneider l. A simple technique for quantitation of low levels of DNA damage in individual cells","volume":"175","author":"NP Singh","year":"1988","journal-title":"Exp. Cell Res"},{"key":"pone.0258115.ref043","doi-asserted-by":"crossref","first-page":"3817","DOI":"10.1038\/s41596-020-0398-1","article-title":"Minimum Information for Reporting on the Comet Assay (MIRCA): recommendations for describing comet assay procedures and results","volume":"15","author":"P M\u00f8ller","year":"2020","journal-title":"Nat. Protoc"},{"key":"pone.0258115.ref044","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/j.mrrev.2007.11.001","article-title":"Impact of the comet assay in radiobiology","volume":"681","author":"PL Olive","year":"2009","journal-title":"Mutat Res"},{"key":"pone.0258115.ref045","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1258\/ebm.2011.011161","article-title":"Antihyperglycemic potentials of a threatened plant, Helonias dioica: antioxidative stress responses and the signaling cascade","volume":"237","author":"D Chakraborty","year":"2012","journal-title":"Exp. Biol. Med"},{"key":"pone.0258115.ref046","doi-asserted-by":"crossref","first-page":"6301","DOI":"10.1074\/jbc.M410647200","article-title":"Sensitization of taxol992 induced apoptosis by curcumin involves down-regulation of nuclear factor-kappaB and the serine\/threonine kinase Akt and is independent of tubulin polymerization","volume":"280","author":"SV Bava","year":"2005","journal-title":"J. Biol. Chem"},{"key":"pone.0258115.ref047","doi-asserted-by":"crossref","first-page":"10375","DOI":"10.1039\/C7NR02770B","article-title":"Nanoparticle delivery of curcumin induces cellular hypoxia and ROS-mediated apoptosis via modulation of Bcl-2\/Bax in human neuroblastoma","volume":"9","author":"I Kalashnikova","year":"2017","journal-title":"Nanoscale"},{"key":"pone.0258115.ref048","doi-asserted-by":"crossref","first-page":"3019","DOI":"10.1039\/C4AY00288A","article-title":"Measurement of DCF fluorescence as a measure of reactive oxygen species in murine islets of Langerhans","volume":"6","author":"X Wang","year":"2014","journal-title":"Analytical Methods"},{"key":"pone.0258115.ref049","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1006\/meth.2001.1262","article-title":"Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method","volume":"25","author":"J Livak K","year":"2001","journal-title":"Methods"},{"key":"pone.0258115.ref050","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/j.biopha.2018.10.088","article-title":"The impact of Keap1\/Nrf2, P38MAPK\/NF-\u03baB and Bax\/Bcl2\/caspase-3 signaling pathways in the protective effects of berberine against methotrexate-induced nephrotoxicity","volume":"109","author":"EHM Hassanein","year":"2019","journal-title":"Biomed. Pharmacother"},{"key":"pone.0258115.ref051","first-page":"1325","article-title":"Coexpression of Inducible Nitric Oxide Synthase and COX-2 in Hepatocellular Carcinoma and Surrounding Liver: Possible Involvement of COX-2 in the Angiogenesis of Hepatitis C Virus-positive Cases","volume":"7","author":"MA Rahman","year":"2001","journal-title":"Clin. Can. Res"},{"key":"pone.0258115.ref052","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1631\/jzus.B0820013","article-title":"T-2 toxin-induced apoptosis involving Fas, p53, Bcl-xL, Bcl-2, Bax and caspase-3 signaling pathways in human chondrocytes","volume":"9","author":"JH Chen","year":"2008","journal-title":"J. Zhejiang Univ. Sci. B"},{"key":"pone.0258115.ref053","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1159\/000459586","article-title":"Revised assay for serum phenyl phosphatase activity using 4-amino1017 antipyrine","volume":"12","author":"A Belfield","year":"1971","journal-title":"Enzyme"},{"key":"pone.0258115.ref054","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1093\/ajcp\/28.1.56","article-title":"A colorimetric method for the determination of serum glutamic oxalacetic and glutamic pyruvic transaminases","volume":"28","author":"S Reitman","year":"1957","journal-title":"Am. J. Clin. Path"},{"key":"pone.0258115.ref055","doi-asserted-by":"crossref","first-page":"1114","DOI":"10.1093\/clinchem\/30.6.1114","article-title":"Creatine kinase MB isoenzymes in serum of patients who undergo cardic surgery","volume":"30","author":"SR Gambino","year":"1984","journal-title":"Clinical Chemistry"},{"key":"pone.0258115.ref056","first-page":"545","article-title":"Colorimetric Method for Determination of Total Lipids","volume":"135","author":"N. Z\u00f6llner","year":"1962","journal-title":"Journal of Experimental Medicine"},{"key":"pone.0258115.ref057","first-page":"142","article-title":"Enzymatic determination of uric acid","volume":"97","author":"D Barham","year":"1972","journal-title":"Analyst"},{"key":"pone.0258115.ref058","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1136\/jcp.13.2.156","article-title":"A rapid and precise method for the determination of urea","volume":"13","author":"JK Fawcett","year":"1960","journal-title":"Journal of Clinical Pathology"},{"key":"pone.0258115.ref059","first-page":"1271","volume-title":"Textbook of clinical chemistry: Edited by N W Tietz","author":"F Vella","year":"1986"},{"key":"pone.0258115.ref060","first-page":"908","article-title":"BioMed-Total Protein, Colorimetric","volume":"23","author":"HL Yatzidis","year":"1987","journal-title":"Endpoint. Clinical Chemistry"},{"key":"pone.0258115.ref061","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1002\/ejp.1119","article-title":"New approach for the treatment of neuropathic pain: Fibroblast growth factor 1 gene-transfected adipose-derived mesenchymal stem cells","volume":"22","author":"F Forouzanfar","year":"2017","journal-title":"Eur. J. Pain"},{"key":"pone.0258115.ref062","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/j.yrtph.2016.02.008","article-title":"Toxicity evaluation of hydroalcoholic extract of Ferula gummosa root","volume":"77","author":"A Ghorbani","year":"2016","journal-title":"Regul Toxicol Pharmacol"},{"key":"pone.0258115.ref063","volume-title":"Elements of X-ray Diffraction","author":"BD Cullity","year":"2001"},{"key":"pone.0258115.ref064","doi-asserted-by":"crossref","first-page":"18050","DOI":"10.1039\/D1RA02382A","article-title":"Tunable electrochemistry and efficient antibacterial activity of plant-mediated copper oxide nanoparticles synthesized by Annona squamosa seed extract for agricultural utility","volume":"11","author":"P Singh","year":"2021","journal-title":"RSC Adv"},{"key":"pone.0258115.ref065","volume-title":"Composite Materials: Properties, Characterization, and Applications","author":"CRC Press","year":"2021","edition":"1"},{"key":"pone.0258115.ref066","volume-title":"Nanomaterials in Bionanotechnology Fundamentals and Applications","author":"CRC Press","year":"2021","edition":"1"},{"key":"pone.0258115.ref067","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1007\/s10971-009-2131-y","article-title":"Synthesis of tin oxide nanoparticles by sol\u2013gel process: effect of solvents on the optical properties","volume":"53","author":"S Gnanam","year":"2010","journal-title":"J. Sol-Gel Sci. Technol"},{"key":"pone.0258115.ref068","doi-asserted-by":"crossref","first-page":"622","DOI":"10.1126\/science.1114397","article-title":"Toxic potential of materials at the nanolevel","volume":"311","author":"A Nel","year":"2006","journal-title":"Science"},{"key":"pone.0258115.ref069","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1186\/s13568-020-01096-2","article-title":"Biosynthesis, characterization of PLGA coated folate-mediated multiple drug loaded copper oxide (CuO) nanoparticles and its cytotoxicity on nasopharyngeal cancer cell lines","volume":"10","author":"LM Guo","year":"2020","journal-title":"AMB Expr"},{"key":"pone.0258115.ref070","doi-asserted-by":"crossref","first-page":"490","DOI":"10.1016\/j.colsurfb.2017.06.025","article-title":"Folic acid conjugated polymeric micelles loaded with a curcumin difluorinated analog for targeting cervical and ovarian cancers","volume":"157","author":"D Luong","year":"2017","journal-title":"Colloids Surf. B Biointerfaces"},{"issue":"8","key":"pone.0258115.ref071","doi-asserted-by":"crossref","first-page":"e00737","DOI":"10.1016\/j.heliyon.2018.e00737","article-title":"Synthesis and characterization of Zinc\/Chitosan-Folic","volume":"4","author":"S Bandara","year":"2018","journal-title":"Heliyon"},{"key":"pone.0258115.ref072","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1016\/j.jallcom.2014.10.009","article-title":"Investigations of optoelectronic properties in DMS SnO2 nanoparticles","volume":"622","author":"V Agrahari","year":"2015","journal-title":"J. Alloys & Comp"},{"key":"pone.0258115.ref073","doi-asserted-by":"crossref","first-page":"3171","DOI":"10.2147\/IJN.S80434","article-title":"Formation of curcumin nanoparticles via solution-enhanced dispersion by supercritical CO2","volume":"10","author":"Z Zhao","year":"2015","journal-title":"Int. J. Nanomed"},{"key":"pone.0258115.ref074","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1016\/j.jmmm.2017.01.040","article-title":"Surface spins disorder in uncoated and SiO2 coated maghemite nanoparticles","volume":"429","author":"F Zeb","year":"2017","journal-title":"Journal of Magnetism and Magnetic Materials"},{"key":"pone.0258115.ref075","doi-asserted-by":"crossref","first-page":"8285","DOI":"10.2147\/IJN.S215142","article-title":"Functional design of pH-responsive folate-targeted polymer-coated gold nanoparticles for drug delivery and in vivo therapy in breast cancer","volume":"14","author":"S Mahalunkar","year":"2019","journal-title":"Int. J. Nanomedicine"},{"issue":"8","key":"pone.0258115.ref076","doi-asserted-by":"crossref","first-page":"e69534","DOI":"10.1371\/journal.pone.0069534","article-title":"Copper Oxide Nanoparticles Induced Mitochondria Mediated Apoptosis in Human Hepatocarcinoma Cells","volume":"8","author":"MA Siddiqui","year":"2013","journal-title":"PLoS ONE"},{"key":"pone.0258115.ref077","doi-asserted-by":"crossref","first-page":"2849","DOI":"10.1039\/D0NJ05884J","article-title":"Potentialities of selenium nanoparticles in biomedical science","volume":"45","author":"V Nayak","year":"2021","journal-title":"New J. Chem"},{"key":"pone.0258115.ref078","doi-asserted-by":"crossref","first-page":"27194","DOI":"10.1039\/D0RA04736H","article-title":"Cerium oxide nanoparticles: properties, biosynthesis and biomedical application","author":"KRB Singh","year":"2020","journal-title":"RSC Adv"},{"issue":"8","key":"pone.0258115.ref079","doi-asserted-by":"crossref","first-page":"20081543","DOI":"10.5185\/amlett.2020.081543","article-title":"Recent Applications of Magnesium Oxide (MgO) Nanoparticles in various domains","volume":"11","author":"M Fernandes","year":"2020","journal-title":"Adv. Mater. Lett"},{"key":"pone.0258115.ref080","doi-asserted-by":"crossref","first-page":"9357","DOI":"10.1074\/jbc.273.16.9357","article-title":"Caspase-3 is required for DNA fragmentation and morphological changes associated with apoptosis","volume":"273","author":"RU Janicke","year":"1998","journal-title":"J. Biol. Chem"},{"key":"pone.0258115.ref081","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1002\/mc.22014","article-title":"Induction of reactive oxygen species generation inhibits epithelial1069 mesenchymal transition and promotes growth arrest in prostate cancer cells","volume":"53","author":"TP Das","year":"2014","journal-title":"Molecular Carcinogenesis"},{"key":"pone.0258115.ref082","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1002\/tox.21879","article-title":"Concentration dependent induction of reactive oxygen species, cell cycle arrest and apoptosis in human liver cells after nickel nanoparticles exposure","volume":"30","author":"J Ahmad","year":"2015","journal-title":"Environmental Toxicology"},{"key":"pone.0258115.ref083","first-page":"a026104","volume-title":"The Cell-Cycle Arrest and Apoptotic Functions of p53 in Tumor Initiation and Progression","author":"J Chen","year":"2016"},{"key":"pone.0258115.ref084","doi-asserted-by":"crossref","first-page":"S4","DOI":"10.1164\/rccm.2206007","article-title":"Reactive oxygen species and cell signaling","volume":"166","author":"H. J. Forman","year":"2002","journal-title":"American Journal of Respiratory and Critical Care Medicine"},{"key":"pone.0258115.ref085","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1039\/C8TX00248G","article-title":"Biocompatibility studies on cerium oxide nanoparticles\u2013combined study for local effects, systemic toxicity and genotoxicity via implantation route","volume":"8","author":"V Kalyanaraman","year":"2019","journal-title":"Toxicol. Res"},{"key":"pone.0258115.ref086","first-page":"600","article-title":"Administration of substances to laboratory animals: routes of administration and factors to consider. J. Am. Assoc","volume":"50","author":"PV Turner","year":"2011","journal-title":"Lab Anim. Sci"},{"key":"pone.0258115.ref087","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1002\/jat.3476","article-title":"Potential applications and human biosafety of nanomaterials used in nanomedicine","volume":"38","author":"H Su","year":"2018","journal-title":"J. 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