Spontaneous CO release from Ru(II)(CO)2-protein complexes in aqueous solution, cells, and mice.
Spontaneous CO release from Ru(II)(CO)2-protein complexes in aqueous solution, cells, and mice.
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DOI：
10.1002/anie.201409344
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发表时间：
2015-01-19
期刊：
影响因子：
--
通讯作者：
Bernardes GJ
中科院分区：
文献类型：
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作者：
Chaves-Ferreira M;Albuquerque IS;Matak-Vinkovic D;Coelho AC;Carvalho SM;Saraiva LM;Romão CC;Bernardes GJ
我们证明，RuII（CO）2-蛋白质复合物，由[fac-RuCl（κ2-H2 NCH 2CO 2）（CO）3]（CORM-3）的水解产物与暴露在蛋白质表面的组氨酸残基反应形成，在水溶液，细胞和小鼠中自发释放CO。CO释放检测质谱（MS）和共聚焦显微镜使用CO响应打开荧光探针。这些发现支持我们的假设，血浆蛋白作为CO载体后，在体内施用CORM-3。 合成牛血清白蛋白（BSA）-RuII（CO）2复合物释放的CO导致癌细胞中细胞因子白介素（IL）-6，IL-10和肿瘤坏死因子（TNF）-α下调。最后，在携带结肠癌肿瘤的小鼠中给予BSA-RuII（CO）2会导致肿瘤处CO积聚增加。我们的数据表明，使用RuII（CO）2-蛋白质复合物作为可行的替代品的安全和空间控制的治疗性CO在体内的交付。
We demonstrate that RuII(CO)2–protein complexes, formed by the reaction of the hydrolytic decomposition products of [fac-RuCl(κ2-H2NCH2CO2)(CO)3] (CORM-3) with histidine residues exposed on the surface of proteins, spontaneously release CO in aqueous solution, cells, and mice. CO release was detected by mass spectrometry (MS) and confocal microscopy using a CO-responsive turn-on fluorescent probe. These findings support our hypothesis that plasma proteins act as CO carriers after in vivo administration of CORM-3. CO released from a synthetic bovine serum albumin (BSA)–RuII(CO)2 complex leads to downregulation of the cytokines interleukin (IL)-6, IL-10, and tumor necrosis factor (TNF)-α in cancer cells. Finally, administration of BSA–RuII(CO)2 in mice bearing a colon carcinoma tumor results in enhanced CO accumulation at the tumor. Our data suggest the use of RuII(CO)2–protein complexes as viable alternatives for the safe and spatially controlled delivery of therapeutic CO in vivo.