Towards Cancer Nanoradiopharmaceuticals—Radioisotope Nanocarrier System for Prostate Cancer Theranostics Based on Radiation-Synthesized Polymer Nanogels
Author:
Rurarz Beata Paulina12ORCID, Urbanek Kinga Anna2ORCID, Karczmarczyk Urszula3ORCID, Raczkowska Joanna1, Habrowska-Górczyńska Dominika Ewa2ORCID, Kozieł Marta Justyna24ORCID, Kowalska Karolina2ORCID, Kadłubowski Sławomir1, Sawicka Agnieszka3ORCID, Maurin Michał3ORCID, Piastowska-Ciesielska Agnieszka Wanda24ORCID, Ulański Piotr1ORCID
Affiliation:
1. Institute of Applied Radiation Chemistry, Faculty of Chemistry, Lodz University of Technology, Wroblewskiego 15, 93-590 Lodz, Poland 2. Medical University of Lodz, Department of Cell Cultures and Genomic Analysis, Zeligowskiego 7/9, 90-752 Lodz, Poland 3. National Centre for Nuclear Research, Radioisotope Centre POLATOM, Andrzeja Soltana 7, 05-400 Otwock, Poland 4. Medical University of Lodz, BRaIn Laboratories, Czechoslowacka 4, 92-216 Lodz, Poland
Abstract
Despite the tremendous development of oncology, prostate cancer remains a debilitating malignancy. One of the most promising approaches to addressing this issue is to exploit the advancements of nanomedicine in combination with well-established nuclear medicine and radiotherapy. Following this idea, we have developed a radioisotope nanocarrier platform of electron-beam-synthesized nanogels based on poly(acrylic acid). We have developed a functionalization protocol, showing the very high (>97%) efficiency of the conjugation in targeting a ligand–bombesin derivative. This engineered peptide can bind gastrin-releasing peptide receptors overexpressed in prostate cancer cells; moreover, it bears a radioisotope-chelating moiety. Our nanoplatform exhibits very promising performance in vitro; the radiolabeled nanocarriers maintained high radiochemical purity of >90% in both the labeling buffer and human serum for up to 14 days. The application of the targeted nanocarrier allowed also effective and specific uptake in PC-3 prostate cancer cells, up to almost 30% after 4 h, which is a statistically significant improvement in comparison to carrier-free radiolabeled peptides. Although our system requires further studies for more promising results in vivo, our study represents a vital advancement in radionanomedicine—one of many steps that will lead to effective therapy for castration-resistant prostate cancer.
Funder
National Science Centre, Poland National Centre of Research and Development, Poland European Social Fund
Subject
Cancer Research,Oncology
Reference83 articles.
1. Lankoff, A., Czerwińska, M., and Kruszewski, M. (2023). Nanoparticle-based radioconjugates for targeted imaging and therapy of prostate cancer. Molecules, 28. 2. Prostate cancer incidence and mortality: Global status and temporal trends in 89 countries from 2000 to 2019;Wang;Front. Public Health,2022 3. Mehtälä, J., Zong, J., Vassilev, Z., Brobert, G., Gabarró, M.S., Stattin, P., and Khanfir, H. (2020). Overall survival and second primary malignancies in men with metastatic prostate cancer. PLoS ONE, 15. 4. Rurarz, B.P., Bukowczyk, M., Gibka, N., Piastowska-Ciesielska, A.W., Karczmarczyk, U., and Ulański, P. (2023). Nanostrategies for therapeutic and diagnostic targeting of gastrin-releasing peptide receptor. Int. J. Mol. Sci., 24. 5. Schollhammer, R., Quintyn Ranty, M.L., de Clermont Gallerande, H., Cavelier, F., Valverde, I.E., Vimont, D., Hindié, E., and Morgat, C. (2023). Theranostics of primary prostate cancer: Beyond PSMA and GRP-R. Cancers, 15.
|
|