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To verify the hypothesis that copper metallodendrimers can form conjugates with anticancer drugs, their complexes were biophysically characterized using zeta potential and zeta size methods. Next, to confirm the existence of a synergetic effect of dendrimers and drugs, in vitro studies were performed. The combination therapy has been applied in two cancer cell lines: MCF-7 (human breast cancer cell line) and HepG2 (human liver carcinoma cell line). The doxorubicin (DOX), methotrexate (MTX) and 5-fluorouracil (5-FU) were more effective against cancer cells when conjugated with copper metallodendrimers. Such combination significantly decreased cancer cell viability when compared to noncomplexed drugs or dendrimers. The incubation of cells with drug\/dendrimer complexes resulted in the increase of the reactive oxygen species (ROS) levels and the depolarization of mitochondrial membranes. Copper ions present in the dendrimer structures enhanced the anticancer properties of the whole nanosystem and improved drug effects, inducing both the apoptosis and necrosis of MCF-7 (human breast cancer cell line) and HepG2 (human liver carcinoma cell line) cancer cells.<\/jats:p>","DOI":"10.3390\/ijms24044076","type":"journal-article","created":{"date-parts":[[2023,2,20]],"date-time":"2023-02-20T03:56:07Z","timestamp":1676865367000},"page":"4076","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Combination of Copper Metallodendrimers with Conventional Antitumor Drugs to Combat Cancer in In Vitro Models"],"prefix":"10.3390","volume":"24","author":[{"given":"Marcin","family":"Ho\u0142ota","sequence":"first","affiliation":[{"name":"Department of General Biophysics, Faculty of Biology & Environmental Protection, University of Lodz, Pomorska 141\/143, 90-236 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8952-469X","authenticated-orcid":false,"given":"Sylwia","family":"Michlewska","sequence":"additional","affiliation":[{"name":"Department of General Biophysics, Faculty of Biology & Environmental Protection, University of Lodz, Pomorska 141\/143, 90-236 Lodz, Poland"},{"name":"Laboratory of Microscopic Imaging & Specialized Biological Techniques, Faculty of Biology & Environmental Protection, University of Lodz, Banacha12\/16, 90-237 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra","family":"Garcia-Gallego","sequence":"additional","affiliation":[{"name":"Department of Organic and Inorganic Chemistry, Research Institute in Chemistry \u201cAndr\u00e9s M. del R\u00edo\u201d (IQAR), Universidad de Alcal\u00e1, 28805 Madrid, Spain"},{"name":"Networking Research Center on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), 28029 Madrid, Spain"},{"name":"Institute Ram\u00f3n y Cajal for Health Research (IRYCIS), 28034 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalia Sanz","family":"del Olmo","sequence":"additional","affiliation":[{"name":"Department of Organic and Inorganic Chemistry, Research Institute in Chemistry \u201cAndr\u00e9s M. del R\u00edo\u201d (IQAR), Universidad de Alcal\u00e1, 28805 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0377-5429","authenticated-orcid":false,"given":"Paula","family":"Ortega","sequence":"additional","affiliation":[{"name":"Department of Organic and Inorganic Chemistry, Research Institute in Chemistry \u201cAndr\u00e9s M. del R\u00edo\u201d (IQAR), Universidad de Alcal\u00e1, 28805 Madrid, Spain"},{"name":"Networking Research Center on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), 28029 Madrid, Spain"},{"name":"Institute Ram\u00f3n y Cajal for Health Research (IRYCIS), 28034 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4676-3743","authenticated-orcid":false,"given":"Maria","family":"Bryszewska","sequence":"additional","affiliation":[{"name":"Department of General Biophysics, Faculty of Biology & Environmental Protection, University of Lodz, Pomorska 141\/143, 90-236 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0418-3935","authenticated-orcid":false,"given":"Francisco Javier","family":"de la Mata","sequence":"additional","affiliation":[{"name":"Department of Organic and Inorganic Chemistry, Research Institute in Chemistry \u201cAndr\u00e9s M. del R\u00edo\u201d (IQAR), Universidad de Alcal\u00e1, 28805 Madrid, Spain"},{"name":"Networking Research Center on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), 28029 Madrid, Spain"},{"name":"Institute Ram\u00f3n y Cajal for Health Research (IRYCIS), 28034 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7227-6864","authenticated-orcid":false,"given":"Maksim","family":"Ionov","sequence":"additional","affiliation":[{"name":"Department of General Biophysics, Faculty of Biology & Environmental Protection, University of Lodz, Pomorska 141\/143, 90-236 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,2,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"7","DOI":"10.3322\/caac.21551","article-title":"Cancer statistics, 2019","volume":"69","author":"Siegel","year":"2019","journal-title":"CA Cancer J. 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