TY - JOUR

T1 - PEGylation of Terminal Ligands as a Route to Decrease the Toxicity of Radiocontrast Re6-Clusters

AU - Pronin, Aleksei S

AU - Pozmogova, Tatiana N

AU - Vorotnikov, Yuri A

AU - Vavilov, Georgy D

AU - Ivanov, Anton A

AU - Yanshole, Vadim V

AU - Tsygankova, Alphiya R

AU - Gusel'nikova, Tatiana Ya

AU - Mironov, Yuri V

AU - Shestopalov, Michael A

N1 - This research was funded by The Council for Grants of the President of the Russian Federation, grant number MD-123.2022.1.3.

PY - 2023/11/21

Y1 - 2023/11/21

N2 - 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-Na2H14[{Re6Q8}(P(C2H4COO)3)6] (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.

AB - 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-Na2H14[{Re6Q8}(P(C2H4COO)3)6] (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.

UR - https://www.scopus.com/record/display.uri?eid=2-s2.0-85179339283&origin=inward&txGid=cb48ac4bcbc6210efc367dac81512ac2

U2 - 10.3390/ijms242316569

DO - 10.3390/ijms242316569

M3 - Article

C2 - 38068892

VL - 24

JO - International Journal of Molecular Sciences

JF - International Journal of Molecular Sciences

SN - 1661-6596

IS - 23

M1 - 16569

ER -