title: Fabrication and toxicity characterization of a hybrid material based on oxidized and aminated MWCNT loaded with carboplatin.
abstract: This study focused on the fabrication and toxicity characterization of a hybrid material-based on the multiple functionalizations of multiwalled carbon nanotubes (MWCNTs) with carboxyl or amino groups and the anti-tumor drug carboplatin (CP). The functionalization was evidenced by Fourier transformed infrared spectroscopy (FTIR) and high performance liquid chromatography (HPLC). The amount of platinum ions released in the simulated body fluid (SBF) was assessed by inductively coupled plasma mass spectrometry (ICP-MS). Cell viability, nanotubes cellular uptake, cell proliferation, superoxide anion production, SOD activity, intracellular glutathione and protein expression of several molecules involved in breast tumor cell survival and death were investigated after 24h exposure. Exposure to the aminated carbon nanotubes loaded with carboplatin resulted in a greater decrease of viability compared to oxidized carbon nanotubes loaded with the same drug, which was in an inversely proportional relationship with the production of superoxide anions in breast cancer cells. The inhibition of Hsp60, Hsp90, p53 and Mdm2 protein expression was induced as a consequence of the cytoprotection mechanism failure. Overexpression of Beclin1 and the reduction of Bcl2 expression were also observed, suggesting that functionalized MWCNT loaded with CP trigger cell death via autophagy in breast cancer cells.
authors.affiliation: University of Bucharest, Faculty of Biology, Department of Biochemistry and Molecular Biology, Splaiul Independentei 91-95, 50095 Bucharest, Romania.
authors.forename: Mihaela
authors.initials: M
authors.lastname: Balas
authors.affiliation: University of Bucharest, Faculty of Biology, Department of Biochemistry and Molecular Biology, Splaiul Independentei 91-95, 50095 Bucharest, Romania.
authors.forename: Sabrina
authors.initials: S
authors.lastname: Constanda
authors.affiliation: University Politehnica of Bucharest, Faculty of Applied Chemistry and Materials Science, 1-7 Polizu, 011061 Bucharest, Romania.
authors.forename: Adriana
authors.initials: A
authors.lastname: Duma-Voiculet
authors.affiliation: University Politehnica of Bucharest, Faculty of Applied Chemistry and Materials Science, 1-7 Polizu, 011061 Bucharest, Romania.
authors.forename: Mariana
authors.initials: M
authors.lastname: Prodana
authors.affiliation: Department of Experimental and Applied Biology, Institute of Life Sciences, Vasile Goldis Western University of Arad, 86 Rebreanu, Arad 310414, Romania; Department of Histology, Faculty of Medicine, Vasile Goldis Western University of Arad, 1 Feleacului, Arad 310396, Romania.
authors.forename: Anca
authors.initials: A
authors.lastname: Hermenean
authors.affiliation: Victor Babes National Institute of Pathology, Bucharest, Splaiul Independenţei 99 - 101, 050096, Romania.
authors.forename: Sevinci
authors.initials: S
authors.lastname: Pop
authors.affiliation: University Politehnica of Bucharest, Faculty of Applied Chemistry and Materials Science, 1-7 Polizu, 011061 Bucharest, Romania.
authors.forename: Ioana
authors.initials: I
authors.lastname: Demetrescu
authors.affiliation: University of Bucharest, Faculty of Biology, Department of Biochemistry and Molecular Biology, Splaiul Independentei 91-95, 50095 Bucharest, Romania. Electronic address: ancadinischiotu@yahoo.com.
authors.forename: Anca
authors.initials: A
authors.lastname: Dinischiotu
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000737:chemistry / Q000633:toxicity*; D016190:Carboplatin / Q000008:administration & dosage / Q000737:chemistry / Q000633:toxicity*; D002460:Cell Line; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004337:Drug Carriers / Q000008:administration & dosage / Q000737:chemistry / Q000633:toxicity*; D005029:Ethylenediamines / Q000737:chemistry; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D046529:Microscopy, Electron, Transmission; D037742:Nanotubes, Carbon / Q000737:chemistry / Q000633:toxicity* / Q000648:ultrastructure; D010084:Oxidation-Reduction; D013482:Superoxide Dismutase / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers; D005029:Ethylenediamines; D037742:Nanotubes, Carbon; D013481:Superoxides; C031234:ethylenediamine; D016190:Carboplatin; D013482:Superoxide Dismutase; D005978:Glutathione
keywords: Autophagy; Carboplatin; Cellular uptake; Heat shock proteins; ICP-MS; MWCNTs