Towards Cancer Nanoradiopharmaceuticals—Radioisotope Nanocarrier System for Prostate Cancer Theranostics Based on Radiation-Synthesized Polymer Nanogels
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,...
Main Authors: | , , , , , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
MDPI AG
2023-11-01
|
Series: | Cancers |
Subjects: | |
Online Access: | https://www.mdpi.com/2072-6694/15/23/5646 |
_version_ | 1797400354964373504 |
---|---|
author | Beata Paulina Rurarz Kinga Anna Urbanek Urszula Karczmarczyk Joanna Raczkowska Dominika Ewa Habrowska-Górczyńska Marta Justyna Kozieł Karolina Kowalska Sławomir Kadłubowski Agnieszka Sawicka Michał Maurin Agnieszka Wanda Piastowska-Ciesielska Piotr Ulański |
author_facet | Beata Paulina Rurarz Kinga Anna Urbanek Urszula Karczmarczyk Joanna Raczkowska Dominika Ewa Habrowska-Górczyńska Marta Justyna Kozieł Karolina Kowalska Sławomir Kadłubowski Agnieszka Sawicka Michał Maurin Agnieszka Wanda Piastowska-Ciesielska Piotr Ulański |
author_sort | Beata Paulina Rurarz |
collection | DOAJ |
description | 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. |
first_indexed | 2024-03-09T01:54:19Z |
format | Article |
id | doaj.art-ef06e5a31cd64135860df36206cb2bba |
institution | Directory Open Access Journal |
issn | 2072-6694 |
language | English |
last_indexed | 2024-03-09T01:54:19Z |
publishDate | 2023-11-01 |
publisher | MDPI AG |
record_format | Article |
series | Cancers |
spelling | doaj.art-ef06e5a31cd64135860df36206cb2bba2023-12-08T15:12:49ZengMDPI AGCancers2072-66942023-11-011523564610.3390/cancers15235646Towards Cancer Nanoradiopharmaceuticals—Radioisotope Nanocarrier System for Prostate Cancer Theranostics Based on Radiation-Synthesized Polymer NanogelsBeata Paulina Rurarz0Kinga Anna Urbanek1Urszula Karczmarczyk2Joanna Raczkowska3Dominika Ewa Habrowska-Górczyńska4Marta Justyna Kozieł5Karolina Kowalska6Sławomir Kadłubowski7Agnieszka Sawicka8Michał Maurin9Agnieszka Wanda Piastowska-Ciesielska10Piotr Ulański11Institute of Applied Radiation Chemistry, Faculty of Chemistry, Lodz University of Technology, Wroblewskiego 15, 93-590 Lodz, PolandMedical University of Lodz, Department of Cell Cultures and Genomic Analysis, Zeligowskiego 7/9, 90-752 Lodz, PolandNational Centre for Nuclear Research, Radioisotope Centre POLATOM, Andrzeja Soltana 7, 05-400 Otwock, PolandInstitute of Applied Radiation Chemistry, Faculty of Chemistry, Lodz University of Technology, Wroblewskiego 15, 93-590 Lodz, PolandMedical University of Lodz, Department of Cell Cultures and Genomic Analysis, Zeligowskiego 7/9, 90-752 Lodz, PolandMedical University of Lodz, Department of Cell Cultures and Genomic Analysis, Zeligowskiego 7/9, 90-752 Lodz, PolandMedical University of Lodz, Department of Cell Cultures and Genomic Analysis, Zeligowskiego 7/9, 90-752 Lodz, PolandInstitute of Applied Radiation Chemistry, Faculty of Chemistry, Lodz University of Technology, Wroblewskiego 15, 93-590 Lodz, PolandNational Centre for Nuclear Research, Radioisotope Centre POLATOM, Andrzeja Soltana 7, 05-400 Otwock, PolandNational Centre for Nuclear Research, Radioisotope Centre POLATOM, Andrzeja Soltana 7, 05-400 Otwock, PolandMedical University of Lodz, Department of Cell Cultures and Genomic Analysis, Zeligowskiego 7/9, 90-752 Lodz, PolandInstitute of Applied Radiation Chemistry, Faculty of Chemistry, Lodz University of Technology, Wroblewskiego 15, 93-590 Lodz, PolandDespite 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.https://www.mdpi.com/2072-6694/15/23/5646prostate cancernanogelsnanocarriersnanoradiopharmaceuticalsbombesingastrin-releasing peptide receptor |
spellingShingle | Beata Paulina Rurarz Kinga Anna Urbanek Urszula Karczmarczyk Joanna Raczkowska Dominika Ewa Habrowska-Górczyńska Marta Justyna Kozieł Karolina Kowalska Sławomir Kadłubowski Agnieszka Sawicka Michał Maurin Agnieszka Wanda Piastowska-Ciesielska Piotr Ulański Towards Cancer Nanoradiopharmaceuticals—Radioisotope Nanocarrier System for Prostate Cancer Theranostics Based on Radiation-Synthesized Polymer Nanogels Cancers prostate cancer nanogels nanocarriers nanoradiopharmaceuticals bombesin gastrin-releasing peptide receptor |
title | Towards Cancer Nanoradiopharmaceuticals—Radioisotope Nanocarrier System for Prostate Cancer Theranostics Based on Radiation-Synthesized Polymer Nanogels |
title_full | Towards Cancer Nanoradiopharmaceuticals—Radioisotope Nanocarrier System for Prostate Cancer Theranostics Based on Radiation-Synthesized Polymer Nanogels |
title_fullStr | Towards Cancer Nanoradiopharmaceuticals—Radioisotope Nanocarrier System for Prostate Cancer Theranostics Based on Radiation-Synthesized Polymer Nanogels |
title_full_unstemmed | Towards Cancer Nanoradiopharmaceuticals—Radioisotope Nanocarrier System for Prostate Cancer Theranostics Based on Radiation-Synthesized Polymer Nanogels |
title_short | Towards Cancer Nanoradiopharmaceuticals—Radioisotope Nanocarrier System for Prostate Cancer Theranostics Based on Radiation-Synthesized Polymer Nanogels |
title_sort | towards cancer nanoradiopharmaceuticals radioisotope nanocarrier system for prostate cancer theranostics based on radiation synthesized polymer nanogels |
topic | prostate cancer nanogels nanocarriers nanoradiopharmaceuticals bombesin gastrin-releasing peptide receptor |
url | https://www.mdpi.com/2072-6694/15/23/5646 |
work_keys_str_mv | AT beatapaulinarurarz towardscancernanoradiopharmaceuticalsradioisotopenanocarriersystemforprostatecancertheranosticsbasedonradiationsynthesizedpolymernanogels AT kingaannaurbanek towardscancernanoradiopharmaceuticalsradioisotopenanocarriersystemforprostatecancertheranosticsbasedonradiationsynthesizedpolymernanogels AT urszulakarczmarczyk towardscancernanoradiopharmaceuticalsradioisotopenanocarriersystemforprostatecancertheranosticsbasedonradiationsynthesizedpolymernanogels AT joannaraczkowska towardscancernanoradiopharmaceuticalsradioisotopenanocarriersystemforprostatecancertheranosticsbasedonradiationsynthesizedpolymernanogels AT dominikaewahabrowskagorczynska towardscancernanoradiopharmaceuticalsradioisotopenanocarriersystemforprostatecancertheranosticsbasedonradiationsynthesizedpolymernanogels AT martajustynakozieł towardscancernanoradiopharmaceuticalsradioisotopenanocarriersystemforprostatecancertheranosticsbasedonradiationsynthesizedpolymernanogels AT karolinakowalska towardscancernanoradiopharmaceuticalsradioisotopenanocarriersystemforprostatecancertheranosticsbasedonradiationsynthesizedpolymernanogels AT sławomirkadłubowski towardscancernanoradiopharmaceuticalsradioisotopenanocarriersystemforprostatecancertheranosticsbasedonradiationsynthesizedpolymernanogels AT agnieszkasawicka towardscancernanoradiopharmaceuticalsradioisotopenanocarriersystemforprostatecancertheranosticsbasedonradiationsynthesizedpolymernanogels AT michałmaurin towardscancernanoradiopharmaceuticalsradioisotopenanocarriersystemforprostatecancertheranosticsbasedonradiationsynthesizedpolymernanogels AT agnieszkawandapiastowskaciesielska towardscancernanoradiopharmaceuticalsradioisotopenanocarriersystemforprostatecancertheranosticsbasedonradiationsynthesizedpolymernanogels AT piotrulanski towardscancernanoradiopharmaceuticalsradioisotopenanocarriersystemforprostatecancertheranosticsbasedonradiationsynthesizedpolymernanogels |