title: Improved cytotoxicity and preserved level of cell death induced in colon cancer cells by doxorubicin after its conjugation with iron-oxide magnetic nanoparticles.
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.
authors.affiliation: Gdańsk University of Technology, Chemical Faculty, Department of Pharmaceutical Technology and Biochemistry, Narutowicza Str. 11/12, 80-233 Gdańsk, Poland. Electronic address: ewa.augustin@pg.gda.pl.
authors.forename: Ewa
authors.initials: E
authors.lastname: Augustin
authors.affiliation: Gdańsk University of Technology, Chemical Faculty, Department of Pharmaceutical Technology and Biochemistry, Narutowicza Str. 11/12, 80-233 Gdańsk, Poland. Electronic address: vbart4@wp.pl.
authors.forename: Bartłomiej
authors.initials: B
authors.lastname: Czubek
authors.affiliation: University of Warsaw, Faculty of Chemistry, Pasteura Str. 1, 02-093 Warsaw, Poland. Electronic address: anowicka@chem.uw.edu.pl.
authors.forename: Anna M
authors.initials: AM
authors.lastname: Nowicka
authors.affiliation: University of Warsaw, Faculty of Chemistry, Pasteura Str. 1, 02-093 Warsaw, Poland. Electronic address: akowalczyk@chem.uw.edu.pl.
authors.forename: Agata
authors.initials: A
authors.lastname: Kowalczyk
authors.affiliation: University of Warsaw, Faculty of Chemistry, Pasteura Str. 1, 02-093 Warsaw, Poland. Electronic address: stojek@chem.uw.edu.pl.
authors.forename: Zbigniew
authors.initials: Z
authors.lastname: Stojek
authors.affiliation: Gdańsk University of Technology, Chemical Faculty, Department of Pharmaceutical Technology and Biochemistry, Narutowicza Str. 11/12, 80-233 Gdańsk, Poland. Electronic address: zofia.mazerska@pg.gda.pl.
authors.forename: Zofia
authors.initials: Z
authors.lastname: Mazerska
mesh_terms: D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D016923:Cell Death / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003110:Colonic Neoplasms; D004317:Doxorubicin / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology; D016503:Drug Delivery Systems; D005290:Ferric Compounds / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology; D019073:HT29 Cells; D006801:Humans; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry
chemical_list: D000903:Antibiotics, Antineoplastic; D005290:Ferric Compounds; C000499:ferric oxide; D004317:Doxorubicin
keywords: Cell death; Doxorubicin; G2/M arrest; Iron magnetic nanoparticles; Nanoparticle-protein aggregates