Electron beam processing of poly(acrylic acid) in the synthesis of targeted cancer nanoradiopharmaceuticals
Beata Rurarz1,2, Joanna Raczkowska1, Kinga A. Urbanek2, Dominika E. Habrowska- Gorczynska2, Marta J. Koziel2, Karolina Kowalska2, Slawomir Kadlubowski1, Michal Maurin3, Agnieszka Sawicka3, Urszula Karczmarczyk3, Agnieszka W. Piastowska- Ciesielska2, Piotr Ulanski1.
1Institute of Applied Radiation Chemistry, Lodz University of Technology, Lodz, Poland; 2Department of Cell Cultures and Genomic Analysis, Medical University of Lodz, Lodz, Poland; 3Radioisotope Centre POLATOM, National Centre for Nuclear Research, Otwock, Poland
Nanotechnology is expected to revolutionize the field of cancer management [1]. Among numerous strategies for nanosystems development, radiation synthesis of nanogels is emerging as relatively simple technique with a great potential. In the radiation method, water-soluble polymers can be chemically crosslinked due to reactive species generated during water radiolysis [2]. Hereby, we explore the radiation method to produce nanomaterials of superior quality for applications in oncological theranostics [3].
We synthesize stable [4] nanogels based on poly(acrylic acid) using fast electrons from linear accelerator. We functionalize them with radioisotope-chelating bombesin derivative with affinity to gastrin releasing peptide receptor, abundantly expressed in many cancers. Chelating moiety enables radiolabelling with β- and γ-emitting nuclides, suitable for eradication of fast dividing cancer cells and diagnostic detection, respectively.
We have found that nanocarriers notably improve in-vitro radioisotope internalization in prostate cancer cells and this effect is greatly driven by the targeting ligand. Significant decrease of prostate cells viability shows therapeutic potential of radiolabelled carriers in comparison to their carrier-free and non-radioactive counterparts. In-vivo studies in general show stability of the radiolabelling, however size of nanoparticles clearly influences the biodistribution. We hope that upon further optimization we will be able to achieve efficient and safe nanosystem able to eradicate prostate tumours also in in-vivo setting.
[1] https://www.cancer.gov/nano/cancer-nanotechnology/clinical-trials
[2] Kadlubowski S, et al. Macromolecules 2003; 36:2484.
[3] Matusiak M, et al. Pharmaceutics 2021; 13:1240
[4] Rurarz B, et al. Nukleonika 2021; 66(4):179