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Functionalized TiO(2) nanoparticles labelled with (225)Ac for targeted alpha radionuclide therapy
The (225)Ac radioisotope exhibits very attractive nuclear properties for application in radionuclide therapy. Unfortunately, the major challenge for radioconjugates labelled with (225)Ac is that traditional chelating moieties are unable to sequester the radioactive daughters in the bioconjugate whic...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer Netherlands
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5861168/ https://www.ncbi.nlm.nih.gov/pubmed/29576738 http://dx.doi.org/10.1007/s11051-018-4181-y |
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author | Cędrowska, Edyta Pruszynski, Marek Majkowska-Pilip, Agnieszka Męczyńska-Wielgosz, Sylwia Bruchertseifer, Frank Morgenstern, Alfred Bilewicz, Aleksander |
author_facet | Cędrowska, Edyta Pruszynski, Marek Majkowska-Pilip, Agnieszka Męczyńska-Wielgosz, Sylwia Bruchertseifer, Frank Morgenstern, Alfred Bilewicz, Aleksander |
author_sort | Cędrowska, Edyta |
collection | PubMed |
description | The (225)Ac radioisotope exhibits very attractive nuclear properties for application in radionuclide therapy. Unfortunately, the major challenge for radioconjugates labelled with (225)Ac is that traditional chelating moieties are unable to sequester the radioactive daughters in the bioconjugate which is critical to minimize toxicity to healthy, non-targeted tissues. In the present work, we propose to apply TiO(2) nanoparticles (NPs) as carrier for (225)Ac and its decay products. The surface of TiO(2) nanoparticles with 25 nm diameter was modified with Substance P (5-11), a peptide fragment which targets NK1 receptors on the glioma cells, through the silan-PEG-NHS linker. Nanoparticles functionalized with Substance P (5-11) were synthesized with high yield in a two-step procedure, and the products were characterized by transmission electron microscopy (TEM), dynamic light scattering (DLS) and thermogravimetric analysis (TGA). The obtained results show that one TiO(2)-bioconjugate nanoparticle contains in average 80 peptide molecules on its surface. The synthesized TiO(2)-PEG-SP(5-11) conjugates were labelled with (225)Ac by ion-exchange reaction on hydroxyl (OH) functional groups on the TiO(2) surface. The labelled bioconjugates almost quantitatively retain (225)Ac in phosphate-buffered saline (PBS), physiological salt and cerebrospinal fluid (CSF) for up to 10 days. The leaching of (221)Fr, a first decay daughter of (225)Ac, in an amount of 30% was observed only in CSF after 10 days. The synthesized (225)Ac-TiO(2)-PEG-SP(5-11) has shown high cytotoxic effect in vitro in T98G glioma cells; therefore, it is a promising new radioconjugate for targeted radionuclide therapy of brain tumours. |
format | Online Article Text |
id | pubmed-5861168 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Springer Netherlands |
record_format | MEDLINE/PubMed |
spelling | pubmed-58611682018-03-22 Functionalized TiO(2) nanoparticles labelled with (225)Ac for targeted alpha radionuclide therapy Cędrowska, Edyta Pruszynski, Marek Majkowska-Pilip, Agnieszka Męczyńska-Wielgosz, Sylwia Bruchertseifer, Frank Morgenstern, Alfred Bilewicz, Aleksander J Nanopart Res Research Paper The (225)Ac radioisotope exhibits very attractive nuclear properties for application in radionuclide therapy. Unfortunately, the major challenge for radioconjugates labelled with (225)Ac is that traditional chelating moieties are unable to sequester the radioactive daughters in the bioconjugate which is critical to minimize toxicity to healthy, non-targeted tissues. In the present work, we propose to apply TiO(2) nanoparticles (NPs) as carrier for (225)Ac and its decay products. The surface of TiO(2) nanoparticles with 25 nm diameter was modified with Substance P (5-11), a peptide fragment which targets NK1 receptors on the glioma cells, through the silan-PEG-NHS linker. Nanoparticles functionalized with Substance P (5-11) were synthesized with high yield in a two-step procedure, and the products were characterized by transmission electron microscopy (TEM), dynamic light scattering (DLS) and thermogravimetric analysis (TGA). The obtained results show that one TiO(2)-bioconjugate nanoparticle contains in average 80 peptide molecules on its surface. The synthesized TiO(2)-PEG-SP(5-11) conjugates were labelled with (225)Ac by ion-exchange reaction on hydroxyl (OH) functional groups on the TiO(2) surface. The labelled bioconjugates almost quantitatively retain (225)Ac in phosphate-buffered saline (PBS), physiological salt and cerebrospinal fluid (CSF) for up to 10 days. The leaching of (221)Fr, a first decay daughter of (225)Ac, in an amount of 30% was observed only in CSF after 10 days. The synthesized (225)Ac-TiO(2)-PEG-SP(5-11) has shown high cytotoxic effect in vitro in T98G glioma cells; therefore, it is a promising new radioconjugate for targeted radionuclide therapy of brain tumours. Springer Netherlands 2018-03-20 2018 /pmc/articles/PMC5861168/ /pubmed/29576738 http://dx.doi.org/10.1007/s11051-018-4181-y Text en © The Author(s) 2018 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. |
spellingShingle | Research Paper Cędrowska, Edyta Pruszynski, Marek Majkowska-Pilip, Agnieszka Męczyńska-Wielgosz, Sylwia Bruchertseifer, Frank Morgenstern, Alfred Bilewicz, Aleksander Functionalized TiO(2) nanoparticles labelled with (225)Ac for targeted alpha radionuclide therapy |
title | Functionalized TiO(2) nanoparticles labelled with (225)Ac for targeted alpha radionuclide therapy |
title_full | Functionalized TiO(2) nanoparticles labelled with (225)Ac for targeted alpha radionuclide therapy |
title_fullStr | Functionalized TiO(2) nanoparticles labelled with (225)Ac for targeted alpha radionuclide therapy |
title_full_unstemmed | Functionalized TiO(2) nanoparticles labelled with (225)Ac for targeted alpha radionuclide therapy |
title_short | Functionalized TiO(2) nanoparticles labelled with (225)Ac for targeted alpha radionuclide therapy |
title_sort | functionalized tio(2) nanoparticles labelled with (225)ac for targeted alpha radionuclide therapy |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5861168/ https://www.ncbi.nlm.nih.gov/pubmed/29576738 http://dx.doi.org/10.1007/s11051-018-4181-y |
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