{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T08:05:49Z","timestamp":1778745949926,"version":"3.51.4"},"reference-count":39,"publisher":"Institute of Physiology of the Czech Academy of Sciences","issue":"S3","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Physiol Res"],"abstract":"<jats:p>The aim of our study was to monitor the antiproliferative\/ cytotoxic and genotoxic effects of both, poly(ethylene glycol)-block-poly(lactic acid) (PEG-b-PLA) and titanium dioxide (TiO2) nanoparticles on the tumor (HT-29, MCF-7, U118MG) and healthy (HEK-293T) cell lines during 2D cultivation and during cultivation in the spheroid form (3D cultivation). Cells or spheroids were cultivated with nanoparticles (0.01, 0.1, 1, 10, 50, and 100 \u03bcg\/ml) for 72 hours. The cytotoxic effect was determined by the MTT test and the genotoxic effect by the comet assay. We found that 2D cultivation of tumor cell lines with PEG-b-PLA and TiO2 nanoparticles had an anti-proliferative effect on human colon cancer cell line HT-29, human breast cancer cell line MCF-7, human glioma cell line U-118MG during 72h cultivation, but not on control\/healthy HEK-293T cells. At the concentrations used, the tested nanoparticles caused no cytotoxic effect on tumor cell lines. Nanoparticles PEG-b-PLA induced significant damage to DNA in HT-29 and MCF-7 cells, while TiO2 nanoparticles in MCF-7 and U-118MG cells. Only PEG-b-PLA nanoparticles caused cytotoxic (IC50 = 7 \u03bcg\/ml) and genotoxic effects on the healthy cell line HEK-293T after 72h cultivation. The cells which were cultivated in spheroid forms were more sensitive to both types of nanoparticles. After 72h cultivation, we observed the cytotoxic effect on both, the tumor and healthy cell lines.<\/jats:p>","DOI":"10.33549\/physiolres.935152","type":"journal-article","created":{"date-parts":[[2023,10,25]],"date-time":"2023-10-25T17:52:28Z","timestamp":1698256348000},"page":"S257-S266","source":"Crossref","is-referenced-by-count":3,"title":["Biological Analyses of the Effects of TiO2 and PEG-b-PLA Nanoparticles on Three-Dimensional Spheroid-Based Tumor"],"prefix":"10.33549","volume":"72","author":[{"given":"K","family":"Ko\u0148\u00e1rikov\u00e1","sequence":"first","affiliation":[{"name":"Institute of Medical Chemistry, Biochemistry and Clinical Biochemistry, Faculty of Medicine, Comenius University, Bratislava, Slovak Republic"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"GM","family":"Gira\u0161kov\u00e1","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"I","family":"\u017dit\u0148anov\u00e1","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M","family":"Dvo\u0159\u00e1kov\u00e1","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"E","family":"Rollerov\u00e1","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S","family":"Scsukov\u00e1","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J","family":"Bizik","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M","family":"Janubov\u00e1","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J","family":"Muchov\u00e1","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"19169","published-online":{"date-parts":[[2023]]},"reference":[{"key":"ref0","doi-asserted-by":"publisher","unstructured":"Kavoosi F, Modaresi F, Sanaei M, Rezaei Z. Medical and dental applications of nanomedicines. J Pathol Microbiol Immunol 2018;126:795-803. https:\/\/doi.org\/10.1111\/apm.12890","DOI":"10.1111\/apm.12890"},{"key":"ref1","doi-asserted-by":"publisher","unstructured":"Hofmann-Amtenbrink M, Grainger DW, Hofmann H. Nanoparticles in medicine: Current challenges facing inorganic nanoparticle toxicity assessments and standardizations. Nanomedicine: Nanotechnology, Biology and Medicine, 2015;11:1689-1694. https:\/\/doi.org\/10.1016\/j.nano.2015.05.005","DOI":"10.1016\/j.nano.2015.05.005"},{"key":"ref2","doi-asserted-by":"crossref","unstructured":"Rizvi SAA and Saleh AM. Applications of nanoparticle systems in drug delivery technology. Saudi Pharm J, 2018;26:64-70. https:\/\/doi.org\/10.1016\/j.jsps.2017.10.012","DOI":"10.1016\/j.jsps.2017.10.012"},{"key":"ref3","doi-asserted-by":"publisher","unstructured":"Liu J, Jiang X, Ashley C, Brinker CJ. Electrostatically mediated liposome fusion and lipid exchange with a nanoparticle-supported bilayer for control of surface charge, drug containment, and delivery. J Am Chem Soc 2009;10;131:7567-7569. https:\/\/doi.org\/10.1021\/ja902039y","DOI":"10.1021\/ja902039y"},{"key":"ref4","doi-asserted-by":"crossref","unstructured":"Friedman AD, Claypool SE, Liu R. The Smart Targeting of Nanoparticles. Curr Pharm Des 2013;19:6315-6329. https:\/\/doi.org\/10.2174\/13816128113199990375","DOI":"10.2174\/13816128113199990375"},{"key":"ref5","doi-asserted-by":"publisher","unstructured":"Czajka M, Sawicki K, Sikorska K, Popek S, Kruszewski M, Kapka-Skrzypczak L. Toxicity of titanium dioxide nanoparticles in central nervous system. Toxicol In Vitro, 2015;29:1042-1052. https:\/\/doi.org\/10.1016\/j.tiv.2015.04.004","DOI":"10.1016\/j.tiv.2015.04.004"},{"key":"ref6","unstructured":"Bahadar H, Maqbool F, Niaz K, Abdollahi. Toxicity of Nanoparticles and an Overview of Current Experimental Models. 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Systemic delivery of blood-brain barrier targeted polymeric nanoparticles enhances delivery to brain tissue. J Drug Target 2015; 23: 736-749. https:\/\/doi.org\/10.3109\/1061186X.2015.1065833","DOI":"10.3109\/1061186x.2015.1065833"},{"key":"ref11","doi-asserted-by":"publisher","unstructured":"Shi H, Magaye R, Castranova V, Zhao J. Titanium dioxide nanoparticles: a review of current toxicological data. Part Fibre Toxicol 2013;10:15. https:\/\/doi.org\/10.1186\/1743-8977-10-15","DOI":"10.1186\/1743-8977-10-15"},{"key":"ref12","doi-asserted-by":"publisher","unstructured":"Lin Z, Monteiro-Riviere NA, Riviere JE. Pharmacokinetics of metallic nanoparticles. Wiley Interdiscip Rev Nanomed Nanobiotechnol 2015;7:189-217. https:\/\/doi.org\/10.1002\/wnan.1304","DOI":"10.1002\/wnan.1304"},{"key":"ref13","doi-asserted-by":"publisher","unstructured":"Grande F, Tucci P. Titanium dioxide nanoparticles: a risk for human health? 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