{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,7]],"date-time":"2026-02-07T19:48:34Z","timestamp":1770493714866,"version":"3.49.0"},"reference-count":81,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2021,11,1]],"date-time":"2021-11-01T00:00:00Z","timestamp":1635724800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Portuguese Science and Technology Foundation (FCT) from the Ministry of Science and Technology (MCTES), through the projects UIDB\/04469\/2020 (CEB strategic fund) and UIDB\/04033\/2020 (CITAB), co-funded by European Funds (PRODER\/COMPETE) and FEDER, under th","award":["UIDB\/04469\/2020 (CEB strategic fund), UIDB\/04033\/2020 (CITAB), MINIATURA 4 for single research activity (grant no: 2020\/04\/X\/ST5\/00789) and by the START 2021 Program"],"award-info":[{"award-number":["UIDB\/04469\/2020 (CEB strategic fund), UIDB\/04033\/2020 (CITAB), MINIATURA 4 for single research activity (grant no: 2020\/04\/X\/ST5\/00789) and by the START 2021 Program"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Materials"],"abstract":"<jats:p>Nanocomposites as drug delivery systems (e.g., metal nanoparticles) are being exploited for several applications in the biomedical field, from therapeutics to diagnostics. Green nanocomposites stand for nanoparticles of biocompatible, biodegradable and non-toxic profiles. When using metal nanoparticles for drug delivery, the question of how hazardous these \u201cvirus-sized particles\u201d can be is posed, due to their nanometer size range with enhanced reactivity compared to their respective bulk counterparts. These structures exhibit a high risk of being internalized by cells and interacting with the genetic material, with the possibility of inducing DNA damage. The Comet Assay, or Single-Cell Gel Electrophoresis (SCGE), stands out for its capacity to detect DNA strand breaks in eukaryotic cells. It has huge potential in the genotoxicity assessment of nanoparticles and respective cells\u2019 interactions. In this review, the Comet assay is described, discussing several examples of its application in the genotoxicity evaluation of nanoparticles commonly administered in a set of routes (oral, skin, inhaled, ocular and parenteral administration). In the nanoparticles boom era, where guidelines for their evaluation are still very limited, it is urgent to ensure their safety, alongside their quality and efficacy. Comet assay or SCGE can be considered an essential tool and a reliable source to achieve a better nanotoxicology assessment of metal nanoparticles used in drug delivery.<\/jats:p>","DOI":"10.3390\/ma14216551","type":"journal-article","created":{"date-parts":[[2021,11,1]],"date-time":"2021-11-01T22:22:24Z","timestamp":1635805344000},"page":"6551","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Genotoxicity Assessment of Metal-Based Nanocomposites Applied in Drug Delivery"],"prefix":"10.3390","volume":"14","author":[{"given":"Sara","family":"Cardoso","sequence":"first","affiliation":[{"name":"Polo das Ci\u00eancias da Sa\u00fade, Departament of Pharmaceutical Technology, Faculty of Pharmacy, University of Coimbra, Azinhaga de Santa Comba, 3000-548 Coimbra, Portugal"}]},{"given":"Classius F.","family":"da Silva","sequence":"additional","affiliation":[{"name":"Instituto de Ci\u00eancias Ambientais, Qu\u00edmicas e Farmac\u00eauticas, Federal University of S\u00e3o Paulo, Rua S\u00e3o Nicolau, 210, Diadema 09913-030, Brazil"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6527-6612","authenticated-orcid":false,"given":"Patr\u00edcia","family":"Severino","sequence":"additional","affiliation":[{"name":"Instituto de Tecnologia e Pesquisa, Universidade Tiradentes, Av. Murilo Dantas, 300, Aracaju 49032-490, Brazil"},{"name":"Post-Graduation Program in Industrial Biotechnology, Universidade Tiradentes, Av. Murilo Dantas, 300, Aracaju 49032-490, Brazil"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7524-9914","authenticated-orcid":false,"given":"Am\u00e9lia M.","family":"Silva","sequence":"additional","affiliation":[{"name":"Centre for Research and Technology of Agro-Environmental and Biological Sciences (CITAB), University of Tr\u00e1s-os Montes e Alto Douro (UTAD), Quinta de Prados, 5001-801 Vila Real, Portugal"},{"name":"Department of Biology and Environment, University of Tr\u00e1s-os-Montes e Alto Douro (UTAD), Quinta de Prados, 5001-801 Vila Real, Portugal"}]},{"given":"Selma B.","family":"Souto","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Hospital de S\u00e3o Jo\u00e3o, Alameda Prof. Hern\u00e2ni Monteiro, 4200-319 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2603-1377","authenticated-orcid":false,"given":"Aleksandra","family":"Zieli\u0144ska","sequence":"additional","affiliation":[{"name":"Polo das Ci\u00eancias da Sa\u00fade, Departament of Pharmaceutical Technology, Faculty of Pharmacy, University of Coimbra, Azinhaga de Santa Comba, 3000-548 Coimbra, Portugal"},{"name":"Institute of Human Genetics, Polish Academy of Sciences, Strzeszy\u0144ska 32, 60-479 Poznan, Poland"}]},{"given":"Jacek","family":"Karczewski","sequence":"additional","affiliation":[{"name":"Department of Environmental Medicine, Poznan University of Medical Sciences, 60-355 Poznan, Poland"},{"name":"Department of Gastroenterology, Dietetics and Internal Diseases, H. Swiecicki University Hospital, Poznan University of Medical Sciences, 60-355 Poznan, Poland"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9737-6017","authenticated-orcid":false,"given":"Eliana B.","family":"Souto","sequence":"additional","affiliation":[{"name":"Polo das Ci\u00eancias da Sa\u00fade, Departament of Pharmaceutical Technology, Faculty of Pharmacy, University of Coimbra, Azinhaga de Santa Comba, 3000-548 Coimbra, Portugal"},{"name":"CEB\u2014Centro de Engenharia Biol\u00f3gica, Campus de Gualtar, Universidade do Minho, 4710-057 Braga, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2021,11,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1306","DOI":"10.7150\/thno.14858","article-title":"The Smart Drug Delivery System and Its Clinical Potential","volume":"6","author":"Liu","year":"2016","journal-title":"Theranostics"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"754","DOI":"10.1002\/bab.1322","article-title":"Silica-based matrices: State of the art and new perspectives for therapeutic drug delivery","volume":"62","author":"Andreani","year":"2015","journal-title":"Biotechnol. Appl. Biochem."},{"key":"ref_3","first-page":"1117","article-title":"Nanotoxicology and nanoparticle safety in biomedical designs","volume":"6","author":"Ai","year":"2011","journal-title":"Int. J. Nanomed."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1016\/j.tox.2013.11.012","article-title":"Genotoxicity of silver and titanium dioxide nanoparticles in bone marrow cells of rats in vivo","volume":"315","author":"Dobrzynska","year":"2014","journal-title":"Toxicology"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1093\/mutage\/gew054","article-title":"Critical review of the current and future challenges associated with advanced in vitro systems towards the study of nanoparticle (secondary) genotoxicity","volume":"32","author":"Evans","year":"2017","journal-title":"Mutagenesis"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1050","DOI":"10.3762\/bjnano.9.98","article-title":"Review on nanoparticles and nanostructured materials: History, sources, toxicity and regulations","volume":"9","author":"Jeevanandam","year":"2018","journal-title":"Beilstein J. Nanotechnol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"S119","DOI":"10.1098\/rsif.2009.0252.focus","article-title":"Nanoparticles, human health hazard and regulation","volume":"7","author":"Seaton","year":"2010","journal-title":"J. R. Soc. Interface"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Soares, S., Sousa, J., Pais, A., and Vitorino, C. (2018). Nanomedicine: Principles, Properties, and Regulatory Issues. Front. Chem., 6.","DOI":"10.3389\/fchem.2018.00360"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Zainol, M., Stoute, J., Almeida, G.M., Rapp, A., Bowman, K.J., Jones, G.D., and ECVAG (2009). Introducing a true internal standard for the Comet assay to minimize intra- and inter-experiment variability in measures of DNA damage and repair. Nucleic Acids Res., 37.","DOI":"10.1093\/nar\/gkp826"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1093\/mutage\/18.2.167","article-title":"Aspects of design and statistical analysis in the Comet assay","volume":"18","author":"Wiklund","year":"2003","journal-title":"Mutagenesis"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1002\/jat.2961","article-title":"Comet assay reveals no genotoxicity risk of cationic solid lipid nanoparticles","volume":"34","author":"Doktorovova","year":"2014","journal-title":"J. Appl. Toxicol."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Azqueta, A., and Dusinska, M. (2015). The use of the comet assay for the evaluation of the genotoxicity of nanomaterials. Front. Genet., 6.","DOI":"10.3389\/fgene.2015.00239"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"2315","DOI":"10.1007\/s00204-016-1767-y","article-title":"Comet assay: An essential tool in toxicological research","volume":"90","author":"Glei","year":"2016","journal-title":"Arch. Toxicol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1093\/mutage\/gei033","article-title":"The in vivo comet assay: Use and status in genotoxicity testing","volume":"20","author":"Hartmann","year":"2005","journal-title":"Mutagenesis"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1385\/MB:26:3:249","article-title":"The comet assay for DNA damage and repair: Principles, applications, and limitations","volume":"26","author":"Collins","year":"2004","journal-title":"Mol. Biotechnol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"861","DOI":"10.3109\/17435390.2015.1130274","article-title":"Overestimation of nanoparticles-induced DNA damage determined by the comet assay","volume":"10","author":"Ferraro","year":"2016","journal-title":"Nanotoxicology"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1093\/mutage\/gen014","article-title":"Ecotoxicological applications and significance of the comet assay","volume":"23","author":"Jha","year":"2008","journal-title":"Mutagenesis"},{"key":"ref_18","first-page":"87","article-title":"Comet assay: A method to evaluate genotoxicity of nano-drug delivery system","volume":"1","author":"Vandghanooni","year":"2011","journal-title":"Bioimpacts"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1002\/(SICI)1098-2280(2000)35:3<206::AID-EM8>3.0.CO;2-J","article-title":"Single cell gel\/comet assay: Guidelines for in vitro and in vivo genetic toxicology testing","volume":"35","author":"Tice","year":"2000","journal-title":"Environ. Mol. Mutagen."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/j.mrgentox.2011.05.010","article-title":"Towards a more reliable comet assay: Optimising agarose concentration, unwinding time and electrophoresis conditions","volume":"724","author":"Azqueta","year":"2011","journal-title":"Mutat. Res."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1080\/00450618.2019.1711177","article-title":"Fluorescent dye-based detection of trace DNA on forensic tapelifts from worn shirts","volume":"53","author":"Krosch","year":"2021","journal-title":"Aust. J. Forensic Sci."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Braafladt, S., Reipa, V., and Atha, D.H. (2016). The Comet Assay: Automated Imaging Methods for Improved Analysis and Reproducibility. Sci. Rep., 6.","DOI":"10.1038\/srep32162"},{"key":"ref_23","unstructured":"(2021, October 12). ThoughtCo. Available online: https:\/\/www.thoughtco.com\/visualizing-dna-375499."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1093\/toxres\/tfaa093","article-title":"Comet assay: A versatile but complex tool in genotoxicity testing","volume":"10","author":"Cordelli","year":"2021","journal-title":"Toxicol. Res."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1136\/oem.2004.013243","article-title":"Nanotoxicology","volume":"61","author":"Donaldson","year":"2004","journal-title":"Occup. Environ. Med."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"S109","DOI":"10.1093\/toxsci\/kfq372","article-title":"The new toxicology of sophisticated materials: Nanotoxicology and beyond","volume":"120","author":"Maynard","year":"2011","journal-title":"Toxicol. Sci."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"723","DOI":"10.1007\/s00204-010-0560-6","article-title":"Nanotoxicology: A perspective and discussion of whether or not in vitro testing is a valid alternative","volume":"85","author":"Clift","year":"2011","journal-title":"Arch. Toxicol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1146\/annurev.pharmtox.010909.105819","article-title":"Close encounters of the small kind: Adverse effects of man-made materials interfacing with the nano-cosmos of biological systems","volume":"50","author":"Shvedova","year":"2010","journal-title":"Annu. Rev. Pharmacol. Toxicol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.taap.2016.02.014","article-title":"Nanotoxicology ten years later: Lights and shadows","volume":"299","author":"Shvedova","year":"2016","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"378","DOI":"10.1080\/15376516.2019.1566425","article-title":"Review of emerging concepts in nanotoxicology: Opportunities and challenges for safer nanomaterial design","volume":"29","author":"Singh","year":"2019","journal-title":"Toxicol. Mech. Methods"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Morigi, V., Tocchio, A., Bellavite Pellegrini, C., Sakamoto, J.H., Arnone, M., and Tasciotti, E. (2012). Nanotechnology in medicine: From inception to market domination. J. Drug Deliv., 2012.","DOI":"10.1155\/2012\/389485"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Sukhanova, A., Bozrova, S., Sokolov, P., Berestovoy, M., Karaulov, A., and Nabiev, I. (2018). Dependence of Nanoparticle Toxicity on Their Physical and Chemical Properties. Nanoscale Res. Lett., 13.","DOI":"10.1186\/s11671-018-2457-x"},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"De Matteis, V. (2017). Exposure to Inorganic Nanoparticles: Routes of Entry, Immune Response, Biodistribution and In Vitro\/In Vivo Toxicity Evaluation. Toxics, 5.","DOI":"10.3390\/toxics5040029"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1080\/10590500802708267","article-title":"Toxicity and environmental risks of nanomaterials: Challenges and future needs","volume":"27","author":"Ray","year":"2009","journal-title":"J. Environ. Sci. Health C Environ. Carcinog. Ecotoxicol. Rev."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"941","DOI":"10.1038\/nbt.3330","article-title":"Principles of nanoparticle design for overcoming biological barriers to drug delivery","volume":"33","author":"Blanco","year":"2015","journal-title":"Nat. Biotechnol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1515\/reveh-2012-0025","article-title":"Nanoparticles in the environment: Stability and toxicity","volume":"27","author":"Kim","year":"2012","journal-title":"Rev. Environ. Health"},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Gatoo, M.A., Naseem, S., Arfat, M.Y., Dar, A.M., Qasim, K., and Zubair, S. (2014). Physicochemical properties of nanomaterials: Implication in associated toxic manifestations. BioMed Res. Int., 2014.","DOI":"10.1155\/2014\/498420"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1093\/mutage\/gen015","article-title":"Statistical issues in the use of the comet assay","volume":"23","author":"Lovell","year":"2008","journal-title":"Mutagenesis"},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Valdiglesias, V., Fern\u00e1ndez-Bert\u00f3lez, N., Lema-Arranz, C., Rodr\u00edguez-Fern\u00e1ndez, R., P\u00e1saro, E., Reis, A.T., Teixeira, J.P., Costa, C., and Laffon, B. (2021). Salivary Leucocytes as In Vitro Model to Evaluate Nanoparticle-Induced DNA Damage. Nanomaterials, 11.","DOI":"10.3390\/nano11081930"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1016\/j.fct.2018.06.061","article-title":"In vitro and in vivo genotoxicity assessment of gold nanoparticles of different sizes by comet and SMART assays","volume":"120","author":"Haza","year":"2018","journal-title":"Food Chem. Toxicol."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Vales, G., Suhonen, S., Siivola, K.M., Savolainen, K.M., Catal\u00e1n, J., and Norppa, H. (2020). Size, Surface Functionalization, and Genotoxicity of Gold Nanoparticles In Vitro. Nanomaterials, 10.","DOI":"10.3390\/nano10020271"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"934","DOI":"10.1002\/jat.2781","article-title":"Genotoxicity evaluation of titanium dioxide nanoparticles using the Ames test and Comet assay","volume":"32","author":"Woodruff","year":"2012","journal-title":"J. Appl. Toxicol."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Cao, S.J., Xu, S., Wang, H.M., Ling, Y., Dong, J., Xia, R.D., and Sun, X.H. (2019). Nanoparticles: Oral Delivery for Protein and Peptide Drugs. AAPS PharmSciTech, 20.","DOI":"10.1208\/s12249-019-1325-z"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"673","DOI":"10.2217\/nnm.16.5","article-title":"The effect of nanoparticle size on in vivo pharmacokinetics and cellular interaction","volume":"11","author":"Hoshyar","year":"2016","journal-title":"Nanomedicine"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1016\/j.nantod.2011.10.001","article-title":"Toxicology and clinical potential of nanoparticles","volume":"6","author":"Yildirimer","year":"2011","journal-title":"Nano Today"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1038\/s41578-019-0110-7","article-title":"Material design for lymph node drug delivery","volume":"4","author":"Schudel","year":"2019","journal-title":"Nat. Rev. Mater."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"821","DOI":"10.1111\/j.2042-7158.1990.tb07033.x","article-title":"Nanoparticle uptake by the rat gastrointestinal mucosa: Quantitation and particle size dependency","volume":"42","author":"Jani","year":"1990","journal-title":"J. Pharm. Pharmacol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"815","DOI":"10.2217\/nnm.11.79","article-title":"In vivo biodistribution of nanoparticles","volume":"6","author":"Almeida","year":"2011","journal-title":"Nanomedicine"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"929","DOI":"10.1016\/j.addr.2007.11.007","article-title":"Clinical toxicities of nanocarrier systems","volume":"60","author":"Takemoto","year":"2008","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"418","DOI":"10.1016\/j.ijpharm.2017.03.016","article-title":"In vitro evaluation of the genotoxicity of poly(anhydride) nanoparticles designed for oral drug delivery","volume":"523","author":"Iglesias","year":"2017","journal-title":"Int. J. Pharm."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1016\/j.yrtph.2017.09.005","article-title":"Acute oral toxicity study of magnesium oxide nanoparticles and microparticles in female albino Wistar rats","volume":"90","author":"Mangalampalli","year":"2017","journal-title":"Regul. Toxicol. Pharmacol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1016\/j.tiv.2010.11.008","article-title":"ROS-mediated genotoxicity induced by titanium dioxide nanoparticles in human epidermal cells","volume":"25","author":"Shukla","year":"2011","journal-title":"Toxicol. Vitro"},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Borm, P.J., Robbins, D., Haubold, S., Kuhlbusch, T., Fissan, H., Donaldson, K., Schins, R., Stone, V., Kreyling, W., and Lademann, J. (2006). The potential risks of nanomaterials: A review carried out for ECETOC. Part Fibre Toxicol., 3.","DOI":"10.1186\/1743-8977-3-11"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"197","DOI":"10.4161\/derm.1.4.9501","article-title":"Nanoparticles and their interactions with the dermal barrier","volume":"1","author":"Schneider","year":"2009","journal-title":"Dermato-Endocrinology"},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Souto, E.B., Ribeiro, A.F., Ferreira, M.I., Teixeira, M.C., Shimojo, A.A.M., Soriano, J.L., Naveros, B.C., Durazzo, A., Lucarini, M., and Souto, S.B. (2020). New Nanotechnologies for the Treatment and Repair of Skin Burns Infections. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21020393"},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Rashid, M.M., Forte Tav\u010der, P., and Tom\u0161i\u010d, B. (2021). Influence of Titanium Dioxide Nanoparticles on Human Health and the Environment. Nanomaterials, 11.","DOI":"10.3390\/nano11092354"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.mrgentox.2016.06.005","article-title":"UVB irradiation-enhanced zinc oxide nanoparticles-induced DNA damage and cell death in mouse skin","volume":"807","author":"Pal","year":"2016","journal-title":"Mutat. Res. Genet. Toxicol. Environ. Mutagen."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"61","DOI":"10.2147\/NSA.S23932","article-title":"A review of mammalian toxicity of ZnO nanoparticles","volume":"5","author":"Vandebriel","year":"2012","journal-title":"Nanotechnol. Sci. Appl."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"3769","DOI":"10.1166\/jnn.2013.7169","article-title":"Zinc oxide nanoparticles induce rat retinal ganglion cell damage through bcl-2, caspase-9 and caspase-12 pathways","volume":"13","author":"Guo","year":"2013","journal-title":"J. Nanosci. Nanotechnol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"3782","DOI":"10.1166\/jnn.2011.4250","article-title":"Zinc oxide nanoparticle induced genotoxicity in primary human epidermal keratinocytes","volume":"11","author":"Sharma","year":"2011","journal-title":"J. Nanosci. Nanotechnol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1016\/j.mrgentox.2013.01.006","article-title":"Quantum dot-related genotoxicity perturbation can be attenuated by PEG encapsulation","volume":"753","author":"Ju","year":"2013","journal-title":"Mutat. Res."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"5421","DOI":"10.2147\/IJN.S138624","article-title":"Quantum dots in imaging, drug delivery and sensor applications","volume":"12","author":"Matea","year":"2017","journal-title":"Int. J. Nanomed."},{"key":"ref_63","first-page":"941","article-title":"Conjugation of quantum dots on carbon nanotubes for medical diagnosis and treatment","volume":"8","author":"Madani","year":"2013","journal-title":"Int. J. Nanomed."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"4792","DOI":"10.1039\/C4CS00532E","article-title":"Quantum dots: Bright and versatile in vitro and in vivo fluorescence imaging biosensors","volume":"44","author":"Wegner","year":"2015","journal-title":"Chem. Soc. Rev."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"703","DOI":"10.1016\/j.addr.2012.09.036","article-title":"Quantum dots as a platform for nanoparticle drug delivery vehicle design","volume":"65","author":"Probst","year":"2013","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1002\/em.21888","article-title":"DNA damage following pulmonary exposure by instillation to low doses of carbon black (Printex 90) nanoparticles in mice","volume":"56","author":"Kyjovska","year":"2015","journal-title":"Environ. Mol. Mutagen."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"45","DOI":"10.2147\/NSA.S3707","article-title":"Gold nanoparticles: From nanomedicine to nanosensing","volume":"1","author":"Chen","year":"2008","journal-title":"Nanotechnol. Sci. Appl."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1355","DOI":"10.1177\/1535370213505964","article-title":"Toxicological profile of small airway epithelial cells exposed to gold nanoparticles","volume":"238","author":"Ng","year":"2013","journal-title":"Exp. Biol. Med."},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Tsai, C.H., Wang, P.Y., Lin, I.C., Huang, H., Liu, G.S., and Tseng, C.L. (2018). Ocular Drug Delivery: Role of Degradable Polymeric Nanocarriers for Ophthalmic Application. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19092830"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1016\/j.ejpb.2016.10.013","article-title":"Lipid nanoparticles (SLN, NLC): Overcoming the anatomical and physiological barriers of the eye\u2014Part II\u2014Ocular drug-loaded lipid nanoparticles","volume":"110","author":"Espina","year":"2017","journal-title":"Eur. J. Pharm. Biopharm."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1016\/j.ejpb.2016.10.009","article-title":"Lipid nanoparticles (SLN, NLC): Overcoming the anatomical and physiological barriers of the eye\u2014Part I\u2014Barriers and determining factors in ocular delivery","volume":"110","author":"Espina","year":"2017","journal-title":"Eur. J. Pharm. Biopharm."},{"key":"ref_72","doi-asserted-by":"crossref","unstructured":"Souto, E.B., Dias-Ferreira, J., Lopez-Machado, A., Ettcheto, M., Cano, A., Camins Espuny, A., Espina, M., Garcia, M.L., and Sanchez-Lopez, E. (2019). Advanced Formulation Approaches for Ocular Drug Delivery: State-Of-The-Art and Recent Patents. Pharmaceutics, 11.","DOI":"10.3390\/pharmaceutics11090460"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1016\/j.ijpharm.2016.02.039","article-title":"Biopharmaceutical evaluation of epigallocatechin gallate-loaded cationic lipid nanoparticles (EGCG-LNs): In vivo, in vitro and ex vivo studies","volume":"502","author":"Fangueiro","year":"2016","journal-title":"Int. J. Pharm."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1093\/mutage\/gex025","article-title":"The comet assay applied to cells of the eye","volume":"33","author":"Azqueta","year":"2018","journal-title":"Mutagenesis"},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"Pierscionek, B.K., Li, Y., Yasseen, A.A., Colhoun, L.M., Schachar, R.A., and Chen, W. (2010). Nanoceria have no genotoxic effect on human lens epithelial cells. Nanotechnology, 21.","DOI":"10.1088\/0957-4484\/21\/3\/035102"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"1912","DOI":"10.1016\/j.biomaterials.2007.12.037","article-title":"Particle size-dependent organ distribution of gold nanoparticles after intravenous administration","volume":"29","author":"Hagens","year":"2008","journal-title":"Biomaterials"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"36","DOI":"10.3109\/17435390.2013.855827","article-title":"Cytotoxicity and genotoxicity assessment of silver nanoparticles in mouse","volume":"8","author":"Li","year":"2014","journal-title":"Nanotoxicology"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"393","DOI":"10.2147\/IJN.S174515","article-title":"Assessment of in vivo genotoxicity of citrated-coated silver nanoparticles via transcriptomic analysis of rabbit liver tissue","volume":"14","author":"Kim","year":"2019","journal-title":"Int. J. Nanomed."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"1199","DOI":"10.1002\/tox.22821","article-title":"The size-dependent genotoxic potentials of titanium dioxide nanoparticles to endothelial cells","volume":"34","author":"Liao","year":"2019","journal-title":"Environ. Toxicol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"1221","DOI":"10.1002\/tox.22628","article-title":"The size-dependent apoptotic effect of titanium dioxide nanoparticles on endothelial cells by the intracellular pathway","volume":"33","author":"Zeng","year":"2018","journal-title":"Environ. Toxicol."},{"key":"ref_81","doi-asserted-by":"crossref","unstructured":"Ansari, M.O., Parveen, N., Ahmad, M.F., Wani, A.L., Afrin, S., Rahman, Y., Jameel, S., Khan, Y.A., Siddique, H.R., and Tabish, M. (2019). Evaluation of DNA interaction, genotoxicity and oxidative stress induced by iron oxide nanoparticles both in vitro and in vivo: Attenuation by thymoquinone. Sci. Rep., 9.","DOI":"10.1038\/s41598-019-43188-5"}],"container-title":["Materials"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1996-1944\/14\/21\/6551\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T07:24:17Z","timestamp":1760167457000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1996-1944\/14\/21\/6551"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,11,1]]},"references-count":81,"journal-issue":{"issue":"21","published-online":{"date-parts":[[2021,11]]}},"alternative-id":["ma14216551"],"URL":"https:\/\/doi.org\/10.3390\/ma14216551","relation":{},"ISSN":["1996-1944"],"issn-type":[{"value":"1996-1944","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,11,1]]}}}