Improved cytotoxicity and preserved level of cell death induced in colon cancer cells by doxorubicin after its conjugation with iron-oxide magnetic nanoparticles. (June 2016)

• Record Type: Journal Article
• Authors: Augustin, Ewa; Czubek, Bartłomiej; Nowicka, Anna M.; Kowalczyk, Agata; Stojek, Zbigniew; Mazerska, Zofia
• Is Part Of: Toxicology in vitro. Volume 33(2016)
• Page Start: 45
• Page End: 53
• Publication Date: 2016-06
• Subjects: CV cyclic voltammetry -- Dox-NPs magnetic (iron-oxide) nanoparticle and doxorubicin conjugates -- DTX docetaxel -- HT29 cells human adenocarcinoma colon cell line -- Np-C6 magnetic nanoparticle functionalized by adipoyl linker -- SEM scanning electron microscopy -- TGA thermogravimetric analysis; Cell death -- Doxorubicin -- G2/M arrest -- Iron magnetic nanoparticles -- Nanoparticle-protein aggregates; Toxicity testing -- In vitro -- Periodicals; Toxicology -- Periodicals; 615.9
• DOI: 10.1016/j.tiv.2016.02.009
• Languages: English
• ISSNs: 0887-2333

Abstract

Abstract: A promising strategy for overcoming the problem of limited efficacy in antitumor drug delivery and in drug release is the use of a nanoparticle-conjugated drug. Doxorubicin (Dox) anticancer chemotherapeutics has been widely studied in this respect, because of severe cardiotoxic side effects. Here, we investigated the cytotoxic effects, the uptake process, the changes in cell cycle progression and the cell death processes in the presence of iron-oxide magnetic nanoparticles (Nps) and doxorubicin conjugates (Dox-Nps) in human colon HT29 cells. The amount of Dox participated in biological action of Dox-Nps was determined by cyclic voltammetry and thermogravimetric measurements. The cytotoxicity of Dox-Nps was shown to be two/three times higher than free Dox, whereas Nps alone did not inhibit cell proliferation. Dox-Nps penetrated cancer cells with higher efficacy than free Dox, what could be a consequence of Dox-Nps aggregation with proteins in culture medium and/or with cell surface. The treatment of HT29 cells with Dox-Nps and Dox at IC50 concentration resulted in G2/M arrest followed by late apoptosis and necrosis. Summing up, the application of iron-oxide magnetic nanoparticles improved Dox-Nps cell penetration compared to free Dox and achieved the cellular response to Dox-Nps conjugates similar to that of Dox alone. Graphical abstract: Highlights: Iron-oxide doxorubicin nanoparticles (Dox-Nps) were applied to improve anticancer drug delivery. Cytotoxicity of Dox-Nps was two/three times higher than free Dox, whereas Nps alone were not cytotoxic against HT29 cells. Dox-Nps were observed to penetrate cancer cells with higher efficacy than free Dox. The treatment of HT-29 cells with Dox-Nps and Dox at IC50 resulted in G2/M arrest followed by apoptosis and necrosis.