PEGylation of Terminal Ligands as a Route to Decrease the Toxicity of Radiocontrast Re<sub>6</sub>-Clusters
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—Na<sub...
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2023-11-01
|
| Series: | International Journal of Molecular Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1422-0067/24/23/16569 |
| _version_ | 1797400091410038784 |
|---|---|
| author | Aleksei S. Pronin Tatiana N. Pozmogova Yuri A. Vorotnikov Georgy D. Vavilov Anton A. Ivanov Vadim V. Yanshole Alphiya R. Tsygankova Tatiana Ya. Gusel’nikova Yuri V. Mironov Michael A. Shestopalov |
| author_facet | Aleksei S. Pronin Tatiana N. Pozmogova Yuri A. Vorotnikov Georgy D. Vavilov Anton A. Ivanov Vadim V. Yanshole Alphiya R. Tsygankova Tatiana Ya. Gusel’nikova Yuri V. Mironov Michael A. Shestopalov |
| author_sort | Aleksei S. Pronin |
| collection | DOAJ |
| description | 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—Na<sub>2</sub>H<sub>14</sub>[{Re<sub>6</sub>Q<sub>8</sub>}(P(C<sub>2</sub>H<sub>4</sub>COO)<sub>3</sub>)<sub>6</sub>] (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. |
| first_indexed | 2024-03-09T01:50:32Z |
| format | Article |
| id | doaj.art-109f4c89eb184c488d174d5b75c07eec |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T01:50:32Z |
| publishDate | 2023-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-109f4c89eb184c488d174d5b75c07eec2023-12-08T15:16:21ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-11-0124231656910.3390/ijms242316569PEGylation of Terminal Ligands as a Route to Decrease the Toxicity of Radiocontrast Re<sub>6</sub>-ClustersAleksei S. Pronin0Tatiana N. Pozmogova1Yuri A. Vorotnikov2Georgy D. Vavilov3Anton A. Ivanov4Vadim V. Yanshole5Alphiya R. Tsygankova6Tatiana Ya. Gusel’nikova7Yuri V. Mironov8Michael A. Shestopalov9Nikolaev Institute of Inorganic Chemistry SB RAS, 3 Acad. Lavrentiev Ave., Novosibirsk 630090, RussiaNikolaev Institute of Inorganic Chemistry SB RAS, 3 Acad. Lavrentiev Ave., Novosibirsk 630090, RussiaNikolaev Institute of Inorganic Chemistry SB RAS, 3 Acad. Lavrentiev Ave., Novosibirsk 630090, RussiaNational Medical Research Center for Circulation Pathology n.a. Academician E.N. Meshalkin, 15 Rechkunovskaya St., Novosibirsk 630055, RussiaNikolaev Institute of Inorganic Chemistry SB RAS, 3 Acad. Lavrentiev Ave., Novosibirsk 630090, RussiaInternational Tomography Center SB RAS, 3a Institutskaya St., Novosibirsk 630090, RussiaNikolaev Institute of Inorganic Chemistry SB RAS, 3 Acad. Lavrentiev Ave., Novosibirsk 630090, RussiaNikolaev Institute of Inorganic Chemistry SB RAS, 3 Acad. Lavrentiev Ave., Novosibirsk 630090, RussiaNikolaev Institute of Inorganic Chemistry SB RAS, 3 Acad. Lavrentiev Ave., Novosibirsk 630090, RussiaNikolaev Institute of Inorganic Chemistry SB RAS, 3 Acad. Lavrentiev Ave., Novosibirsk 630090, RussiaThe 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—Na<sub>2</sub>H<sub>14</sub>[{Re<sub>6</sub>Q<sub>8</sub>}(P(C<sub>2</sub>H<sub>4</sub>COO)<sub>3</sub>)<sub>6</sub>] (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.https://www.mdpi.com/1422-0067/24/23/16569octahedral chalcogenide rhenium clusterphosphinePEGylationcytotoxicityacute toxicityX-ray contrast media |
| spellingShingle | Aleksei S. Pronin Tatiana N. Pozmogova Yuri A. Vorotnikov Georgy D. Vavilov Anton A. Ivanov Vadim V. Yanshole Alphiya R. Tsygankova Tatiana Ya. Gusel’nikova Yuri V. Mironov Michael A. Shestopalov PEGylation of Terminal Ligands as a Route to Decrease the Toxicity of Radiocontrast Re<sub>6</sub>-Clusters International Journal of Molecular Sciences octahedral chalcogenide rhenium cluster phosphine PEGylation cytotoxicity acute toxicity X-ray contrast media |
| title | PEGylation of Terminal Ligands as a Route to Decrease the Toxicity of Radiocontrast Re<sub>6</sub>-Clusters |
| title_full | PEGylation of Terminal Ligands as a Route to Decrease the Toxicity of Radiocontrast Re<sub>6</sub>-Clusters |
| title_fullStr | PEGylation of Terminal Ligands as a Route to Decrease the Toxicity of Radiocontrast Re<sub>6</sub>-Clusters |
| title_full_unstemmed | PEGylation of Terminal Ligands as a Route to Decrease the Toxicity of Radiocontrast Re<sub>6</sub>-Clusters |
| title_short | PEGylation of Terminal Ligands as a Route to Decrease the Toxicity of Radiocontrast Re<sub>6</sub>-Clusters |
| title_sort | pegylation of terminal ligands as a route to decrease the toxicity of radiocontrast re sub 6 sub clusters |
| topic | octahedral chalcogenide rhenium cluster phosphine PEGylation cytotoxicity acute toxicity X-ray contrast media |
| url | https://www.mdpi.com/1422-0067/24/23/16569 |
| work_keys_str_mv | AT alekseispronin pegylationofterminalligandsasaroutetodecreasethetoxicityofradiocontrastresub6subclusters AT tatiananpozmogova pegylationofterminalligandsasaroutetodecreasethetoxicityofradiocontrastresub6subclusters AT yuriavorotnikov pegylationofterminalligandsasaroutetodecreasethetoxicityofradiocontrastresub6subclusters AT georgydvavilov pegylationofterminalligandsasaroutetodecreasethetoxicityofradiocontrastresub6subclusters AT antonaivanov pegylationofterminalligandsasaroutetodecreasethetoxicityofradiocontrastresub6subclusters AT vadimvyanshole pegylationofterminalligandsasaroutetodecreasethetoxicityofradiocontrastresub6subclusters AT alphiyartsygankova pegylationofterminalligandsasaroutetodecreasethetoxicityofradiocontrastresub6subclusters AT tatianayaguselnikova pegylationofterminalligandsasaroutetodecreasethetoxicityofradiocontrastresub6subclusters AT yurivmironov pegylationofterminalligandsasaroutetodecreasethetoxicityofradiocontrastresub6subclusters AT michaelashestopalov pegylationofterminalligandsasaroutetodecreasethetoxicityofradiocontrastresub6subclusters |