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Article

Trastuzumab Modified Barium Ferrite Magnetic Nanoparticles Labeled with Radium-223: A New Potential Radiobioconjugate for Alpha Radioimmunotherapy

1
Institute of Nuclear Chemistry and Technology, Dorodna 16 Str., 03-195 Warsaw, Poland
2
Faculty of Chemistry, University of Warsaw, Pasteura 1, 02-093 Warsaw, Poland
3
Department of Immunohematology, Centre of Postgraduate Medical Education, Marymoncka 99/103, 01-813 Warsaw, Poland
4
European Commission, Joint Research Centre, Directorate for Nuclear Safety and Security, 76125 Karlsruhe, Germany
*
Author to whom correspondence should be addressed.
Nanomaterials 2020, 10(10), 2067; https://doi.org/10.3390/nano10102067
Received: 18 September 2020 / Revised: 6 October 2020 / Accepted: 16 October 2020 / Published: 20 October 2020
(This article belongs to the Special Issue Isotopes Labeled Nanoparticles)
Barium ferrite nanoparticles (BaFeNPs) were investigated as vehicles for 223Ra radionuclide in targeted α-therapy. BaFe nanoparticles were labeled using a hydrothermal Ba2+ cations replacement by 223Ra with yield reaching 61.3 ± 1.8%. Radiolabeled nanoparticles were functionalized with 3-phosphonopropionic acid (CEPA) linker followed by covalent conjugation to trastuzumab (Herceptin®). Thermogravimetric analysis and radiometric method with the use of [131I]-labeled trastuzumab revealed that on average 19–21 molecules of trastuzumab are attached to the surface of one BaFe–CEPA nanoparticle. The hydrodynamic diameter of BaFe–CEPA–trastuzumab conjugate is 99.9 ± 3.0 nm in water and increases to 218.3 ± 3.7 nm in PBS buffer, and the zeta potential varies from +27.2 ± 0.7 mV in water to −8.8 ± 0.7 in PBS buffer. The [223Ra]BaFe–CEPA–trastuzumab radiobioconjugate almost quantitatively retained 223Ra (>98%) and about 96% of 211Bi and 94% of 211Pb over 30 days. The obtained radiobioconjugate exhibited high affinity, cell internalization and cytotoxicity towards the human ovarian adenocarcinoma SKOV-3 cells overexpressing HER2 receptor. Confocal studies indicated that [223Ra]BaFe–CEPA–trastuzumab was located in peri-nuclear space. High cytotoxicity of the [223Ra]BaFe–CEPA–trastuzumab bioconjugate was confirmed by radiotoxicity studies on SKOV-3 cell monolayers and 3D-spheroids. In addition, the magnetic properties of the radiobioconjugate should allow for its use in guide drug delivery driven by magnetic field gradient. View Full-Text
Keywords: alpha radioimmunotherapy; radium-223; barium ferrite alpha radioimmunotherapy; radium-223; barium ferrite
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MDPI and ACS Style

Gawęda, W.; Pruszyński, M.; Cędrowska, E.; Rodak, M.; Majkowska-Pilip, A.; Gaweł, D.; Bruchertseifer, F.; Morgenstern, A.; Bilewicz, A. Trastuzumab Modified Barium Ferrite Magnetic Nanoparticles Labeled with Radium-223: A New Potential Radiobioconjugate for Alpha Radioimmunotherapy. Nanomaterials 2020, 10, 2067. https://doi.org/10.3390/nano10102067

AMA Style

Gawęda W, Pruszyński M, Cędrowska E, Rodak M, Majkowska-Pilip A, Gaweł D, Bruchertseifer F, Morgenstern A, Bilewicz A. Trastuzumab Modified Barium Ferrite Magnetic Nanoparticles Labeled with Radium-223: A New Potential Radiobioconjugate for Alpha Radioimmunotherapy. Nanomaterials. 2020; 10(10):2067. https://doi.org/10.3390/nano10102067

Chicago/Turabian Style

Gawęda, Weronika, Marek Pruszyński, Edyta Cędrowska, Magdalena Rodak, Agnieszka Majkowska-Pilip, Damian Gaweł, Frank Bruchertseifer, Alfred Morgenstern, and Aleksander Bilewicz. 2020. "Trastuzumab Modified Barium Ferrite Magnetic Nanoparticles Labeled with Radium-223: A New Potential Radiobioconjugate for Alpha Radioimmunotherapy" Nanomaterials 10, no. 10: 2067. https://doi.org/10.3390/nano10102067

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