Cellular uptake and cytotoxicity of a near-IR fluorescent corrole-TiO2 nanoconjugate.

Cellular uptake and cytotoxicity of a near-IR fluorescent corrole-TiO2 nanoconjugate.
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DOI:
10.1016/j.jinorgbio.2014.06.015
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发表时间:
2014-11
影响因子:
3.9
通讯作者:
Sorasaenee K
Sorasaenee K
中科院分区:
生物学2区
文献类型:
--
作者:
Blumenfeld CM;Sadtler BF;Fernandez GE;Dara L;Nguyen C;Alonso-Valenteen F;Medina-Kauwe L;Moats RA;Lewis NS;Grubbs RH;Gray HB;Sorasaenee K

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我们正在研究荧光金属配位-二氧化钛纳米结合物作为潜在的近红外光学造影剂在体外对癌症和正常细胞系的生物和生物医学成像作用和影响。制备了小分子2,17-bis(chlorosulfonyl)-5,10,15-tris(pentafluorophenyl)corrolato铝(III)标记的纳米二氧化钛(1-Al-TiO2光催化剂)。用透射电子显微镜和积分球电子吸收光谱对纳米粒子1-Al-TiO2进行了表征。三种不同的纳米二氧化钛样品(裸样、过氧化氢蚀刻样品和1-Al功能化样品)的透射电子显微镜图像显示出相似的形状和大小,1-Al-TiO2的平均直径为29 nm。1-Al在二氧化钛表面的负载量约为20-40mg1-Al/g二氧化钛。以不同浓度的纳米偶联物1-Al-Ti02为造影剂,对荧光素酶基因修饰的原代人胶质母细胞瘤U87-Luc细胞进行了共聚焦荧光显微镜研究。CFM图像显示,即使在低剂量(0.02-2微克/毫升)的癌细胞内也发现了1-Al-二氧化钛,并定位于胞浆中。不同剂量的1-Al-TiO224 h后对U87-Luc细胞的细胞毒作用很小,低剂量(0.0003-3µg/mL1-Al-Ti02)的原代小鼠肝细胞也有类似的观察结果。较长的孵育时间(U87-Luc在48和72 h后)和较高剂量(>20µg/mL1-Al-TiO2U87-Luc和>3µg/mL1-Al-TiO2PMH)均显示细胞存活率下降。摘要图解摘要1-Al-TiO2CoRole纳米结合物内含于胶质母细胞瘤U87-Luc细胞内的荧光(以红色显示)。
We are investigating the biological and biomedical imaging roles and impacts of fluorescent metallocorrole-TiO2 nanoconjugates as potential near-infrared optical contrast agents in vitro in cancer and normal cell lines. The TiO2 nanoconjugate labeled with the small molecule 2,17-bis(chlorosulfonyl)-5,10,15-tris(pentafluorophenyl)corrolato aluminum(III) (1-Al-TiO2) was prepared. The nanoparticle 1-Al-TiO2 was characterized by transmission electron microscopy (TEM) and integrating-sphere electronic absorption spectroscopy. TEM images of three different samples of TiO2 nanoparticles (bare, H2O2 etched, and 1-Al functionalized) showed similarity in shapes and sizes with an average diameter of 29 nm for 1-Al-TiO2. Loading of 1-Al on the TiO2 surfaces was determined to be ca. 20–40 mg 1-Al/g TiO2. Confocal fluorescence microscopy (CFM) studies of luciferase-transfected primary human glioblastoma U87-Luc cells treated with the nanoconjugate 1-Al-TiO2 as the contrast agent in various concentrations were performed. The CFM images revealed that 1-Al-TiO2 was found inside the cancer cells even at low doses (0.02–2 µg/mL) and localized in the cytosol. Bioluminescence studies of the U87-Luc cells exposed to various amounts of 1-Al-TiO2 showed minimal cytotoxic effects even at higher doses (2–2000 µg/mL) after 24 h. A similar observation was made using primary mouse hepatocytes (PMH) treated with 1-Al-TiO2 at low doses (0.0003–3 µg/mL). Longer incubation times (after 48 and 72 h for U87-Luc) and higher doses (> 20 µg/mL 1-Al-TiO2 for U87-Luc and > 3 µg/mL 1-Al-TiO2 for PMH) showed decreased cell viability. Synopsis for the graphic abstract Fluorescence (shown in red) from the corrole nanoconjugate 1-Al-TiO2 internalized in the glioblastoma U87-Luc cell.