Fabrication and toxicity characterization of a hybrid material based on oxidized and aminated MWCNT loaded with carboplatin

被引:16
作者
Balas, Mihaela [1 ]
Constanda, Sabrina [1 ]
Duma-Voiculet, Adriana [2 ]
Prodana, Mariana [2 ]
Hermenean, Anca [3 ,4 ]
Pop, Sevinci [5 ]
Demetrescu, Ioana [2 ]
Dinischiotu, Anca [1 ]
机构
[1] Univ Bucharest, Fac Biol, Dept Biochem & Mol Biol, Splaiul Independentei 91-95, Bucharest 50095, Romania
[2] Univ Politehn Bucuresti, Fac Appl Chem & Mat Sci, 1-7 Polizu, Bucharest 011061, Romania
[3] Vasile Goldis Western Univ Arad, Inst Life Sci, Dept Expt & Appl Biol, 86 Rebreanu, Arad 310414, Romania
[4] Vasile Goldis Western Univ Arad, Fac Med, Dept Histol, 1 Feleacului, Arad 310396, Romania
[5] Victor Babes Natl Inst Pathol, Splaiul Independentei 99-101, Bucharest 050096, Romania
关键词
MWCNTs; Carboplatin; ICP-MS; Cellular uptake; Heat shock proteins; Autophagy; BREAST-CANCER CELLS; MULTIWALLED CARBON NANOTUBES; TUMOR-SUPPRESSOR GENE; HEAT-SHOCK PROTEINS; CHEMOTHERAPEUTIC-AGENTS; OXIDATIVE STRESS; DOWN-REGULATION; DRUG-DELIVERY; AUTOPHAGY; HSP90;
D O I
10.1016/j.tiv.2016.09.011
中图分类号
R99 [毒物学(毒理学)];
学科分类号
100405 ;
摘要
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 antitumor 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 24 h 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. (C) 2016 Elsevier Ltd. All rights reserved.
引用
收藏
页码:189 / 200
页数:12
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