Nikolaev Institute of Inorganic Chemistry SB RAS, 3 Acad. Lavrentiev Ave., Novosibirsk 630090, Russia.
National Medical Research Center for Circulation Pathology n.a. Academician E.N. Meshalkin, 15 Rechkunovskaya St., Novosibirsk 630055, Russia.
Int J Mol Sci. 2023 Nov 21;24(23):16569. doi: 10.3390/ijms242316569.
The development of novel radiocontrast agents, mainly used for the visualization of blood vessels, is still an emerging task due to the variety of side effects of conventional X-ray contrast media. Recently, we have shown that octahedral chalcogenide rhenium clusters with phosphine ligands-NaH[{ReQ}(P(CHCOO))] (Q = S, Se)-can be considered as promising X-ray contrast agents if their relatively high toxicity related to the high charge of the complexes can be overcome. To address this issue, we propose one of the most widely used methods for tuning the properties of proteins and peptides-PEGylation (PEG is polyethylene glycol). The reaction between the clusters and PEG-400 was carried out in acidic aqueous media and resulted in the binding of up to five carboxylate groups with PEG. The study of cytotoxicity against Hep-2 cells and acute toxicity in mice showed a twofold reduction in toxicity after PEGylation, demonstrating the success of the strategy chosen. Finally, the compound obtained has been used for the visualization of blood vessels of laboratory rats by angiography and computed tomography.
新型造影剂的开发主要用于血管显影，由于传统 X 射线造影剂存在多种副作用，因此仍然是一个新兴任务。最近，我们已经表明，如果可以克服与配合物高电荷相关的较高毒性，具有膦配体的八面体硫属元素铼簇-NaH[{ReQ}(P(CHCOO))]（Q = S，Se）可以被认为是有前途的 X 射线造影剂。为了解决这个问题，我们提出了一种最广泛使用的蛋白质和肽性质调节方法-聚乙二醇化（PEG 是聚乙二醇）。在酸性水介质中进行了簇与 PEG-400 的反应，导致多达五个羧酸盐与 PEG 结合。对 Hep-2 细胞的细胞毒性和小鼠的急性毒性研究表明，聚乙二醇化后毒性降低了两倍，证明了所选策略的成功。最后，通过血管造影术和计算机断层扫描，将所获得的化合物用于实验室大鼠的血管显影。
