Towards Cancer Nanoradiopharmaceuticals-Radioisotope Nanocarrier System for Prostate Cancer Theranostics Based on Radiation-Synthesized Polymer Nanogels

Beata Paulina Rurarz, Kinga Anna Urbanek, Urszula Karczmarczyk, Joanna Raczkowska, Dominika Ewa Habrowska-Gorczynska, Marta Justyna Koziel, Karolina Kowalska, Slawomir Kadlubowski, Agnieszka Sawicka, Michal Maurin, Agnieszka Wanda Piastowska-Ciesielska, Piotr Ulanski

CANCERS(2023)

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摘要
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.
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关键词
prostate cancer,nanogels,nanocarriers,nanoradiopharmaceuticals,bombesin,gastrin-releasing peptide receptor,radiation synthesis,poly(acrylic acid),preclinical study
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