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|Title:||Functionalized TiO2 nanoparticles labelled with 225Ac for targeted alpha radionuclide therapy|
|Authors:||CEDROWSKA EDYTA; PRUSZYNSKI MAREK; MAJKOWSKA PILIP AGNIESZKA; MECZYNSKA-WIELGOSZ SYLWIA; BRUCHERTSEIFER FRANK; MORGENSTERN ALFRED; BILEWICZ ALEKSANDER|
|Citation:||JOURNAL OF NANOPARTICLE RESEARCH vol. 20 no. 83|
|Type:||Articles in periodicals and books|
|Abstract:||The 225Ac radioisotope exhibits very attractive nuclear properties for application in radionuclide therapy. Unfortunately, the major challenge for radioconjugates labelled with 225Ac 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 TiO2 nanoparticles (NPs) as carrier for 225Ac and its decay products. The surface of TiO2 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 TiO2-bioconjugate nanoparticle contains in average 80 peptide molecules on its surface. The synthesized TiO2-PEG-SP(5-11) conjugates were labelled with 225Ac by ion-exchange reaction on hydroxyl (OH) functional groups on the TiO2 surface. The labelled bioconjugates almost quantitatively retain 225Ac in phosphate-buffered saline (PBS), physiological salt and cerebrospinal fluid (CSF) for up to 10 days. The leaching of 221Fr, a first decay daughter of 225Ac, in an amount of 30% was observed only in CSF after 10 days. The synthesized 225Ac-TiO2-PEG-SP(5-11) have shown high cytotoxic effect in vitro in T98G glioma cells; therefore, it is a promising new radioconjugate for targeted radionuclide therapy of brain tumours.|
|JRC Directorate:||Nuclear Safety and Security|
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