Synthesis and in vitro evaluation of BBB permeability, tumor cell uptake, and cytotoxicity of a series of carboranylporphyrin conjugates.
Synthesis and in vitro evaluation of BBB permeability, tumor cell uptake, and cytotoxicity of a series of carboranylporphyrin conjugates.
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DOI：
10.1021/jm500786c
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发表时间：
2014-08-14
影响因子：
7.3
通讯作者：
Vicente MG
中科院分区：
文献类型：
--
作者：
Bhupathiraju NV;Hu X;Zhou Z;Fronczek FR;Couraud PO;Romero IA;Weksler B;Vicente MG
合成了一系列由多胺、葡萄糖、精氨酸、三乙二醇和Tyr-d-Arg-Phe-β-Ala（YRFA）肽组成的三[（对碳硼烷甲硫基）四氟苯基]卟啉配合物。研究了这些缀合物在人hCMEC/D3脑内皮细胞中的BBB渗透性，并使用人胶质瘤T98 G细胞评估了它们的细胞毒性和摄取。为了比较，还合成了对称的四[（对碳硼烷甲硫基）四氟苯基]卟啉，并得到了它的晶体结构。所有卟啉缀合物对T98 G细胞显示低暗细胞毒性（IC 50> 400 μM）和低光毒性（IC 50> 100 μM，在1.5 J/cm 2下）。所有缀合物被T98 G细胞有效地摄取，特别是阳离子多胺和精氨酸缀合物，并且定位于多个细胞器中，包括线粒体和溶酶体。所有的化合物显示出相对较低的体外血脑屏障通透性相比，荧光黄，因为它们的较高的分子量，疏水性，并在溶液中聚集的趋势。在该系列中，支链多胺和YRFA缀合物显示出最高的渗透系数，而葡萄糖缀合物显示出最低的渗透系数。
A series of tri[(p-carboranylmethylthio)tetrafluorophenyl]porphyrin conjugates of linear and branched polyamines, glucose, arginine, tri(ethylene glycol), and Tyr-d-Arg-Phe-β-Ala (YRFA) peptide were synthesized. These conjugates were investigated for their BBB permeability in human hCMEC/D3 brain endothelial cells, and their cytotoxicity and uptake were assessed using human glioma T98G cells. For comparison purposes, a symmetric tetra[(p-carboranylmethylthio)tetrafluorophenyl]porphyrin was also synthesized, and its crystal structure was obtained. All porphyrin conjugates show low dark cytotoxicity (IC50 > 400 μM) and low phototoxicity (IC50 > 100 μM at 1.5 J/cm2) toward T98G cells. All conjugates were efficiently taken up by T98G cells, particularly the cationic polyamine and arginine conjugates, and were localized in multiple cellular organelles, including mitochondria and lysosomes. All compounds showed relatively low in vitro BBB permeability compared with that of lucifer yellow because of their higher molecular weight, hydrophobicity, and tendency for aggregation in solution. Within this series, the branched polyamine and YRFA conjugates showed the highest permeability coefficient, whereas the glucose conjugate showed the lowest permeability coefficient.
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影响因子：
4.3
作者：
Hao, Erhong;Sibrian-Vazquez, Martha;Vicente, M. Graca H.
通讯作者：
Vicente, M. Graca H.
影响因子：
3.9
作者：
Kawabata S;Yang W;Barth RF;Wu G;Huo T;Binns PJ;Riley KJ;Ongayi O;Gottumukkala V;Vicente MG
通讯作者：
Vicente MG
DOI：
10.1016/j.jphotobiol.2007.09.012
发表时间：
2007-12-14
影响因子：
5.4
作者：
Fabris, Clara;Vicente, M. Graca H.;Soncin, Marina
通讯作者：
Soncin, Marina
影响因子：
3.5
作者：
Guillaume, Garcia;Sarrazy, Vincent;Krausz, Pierre
通讯作者：
Krausz, Pierre
影响因子：
8.8
作者：
Faria, Ana;Meireles, Manuela;Calhau, Conceicao
通讯作者：
Calhau, Conceicao