Cargando…
Dual enhancement in the radiosensitivity of prostate cancer through nanoparticles and chemotherapeutics
BACKGROUND: Radiotherapy (RT) is an essential component in the treatment regimens for many cancer patients. However, the dose escalation required to improve curative results is hindered due to the normal tissue toxicity that is induced. The introduction of radiosensitizers to RT treatment is an aven...
Autores principales: | , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer Vienna
2023
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10539438/ https://www.ncbi.nlm.nih.gov/pubmed/37781236 http://dx.doi.org/10.1186/s12645-023-00228-0 |
_version_ | 1785113501243539456 |
---|---|
author | Jackson, Nolan Hill, Iona Alhussan, Abdulaziz Bromma, Kyle Morgan, Jessica Abousaida, Belal Zahra, Yasmin Mackeyev, Yuri Beckham, Wayne Herchko, Steven Krishnan, Sunil Chithrani, Devika Basnagge |
author_facet | Jackson, Nolan Hill, Iona Alhussan, Abdulaziz Bromma, Kyle Morgan, Jessica Abousaida, Belal Zahra, Yasmin Mackeyev, Yuri Beckham, Wayne Herchko, Steven Krishnan, Sunil Chithrani, Devika Basnagge |
author_sort | Jackson, Nolan |
collection | PubMed |
description | BACKGROUND: Radiotherapy (RT) is an essential component in the treatment regimens for many cancer patients. However, the dose escalation required to improve curative results is hindered due to the normal tissue toxicity that is induced. The introduction of radiosensitizers to RT treatment is an avenue that is currently being explored to overcome this issue. By introducing radiosensitizers into tumor sites, it is possible to preferentially enhance the local dose deposited. Gold nanoparticles (GNPs) are a potential candidate that have shown great promise in increasing the radiosensitivity of cancer cells through an enhancement in DNA damage. Furthermore, docetaxel (DTX) is a chemotherapeutic agent that arrests cells in the G2/M phase of the cell cycle, the phase most sensitive to radiation damage. We hypothesized that by incorporating DTX to GNP-enhanced radiotherapy treatment, we could further improve the radiosensitization experienced by cancer cells. To assess this strategy, we analyzed the radiotherapeutic effects on monolayer cell cultures in vitro, as well as on a mice prostate xenograft model in vivo while using clinically feasible concentrations for both GNPs and DTX. RESULTS: The introduction of DTX to GNP-enhanced radiotherapy further increased the radiotherapeutic effects experienced by cancer cells. A 38% increase in DNA double-strand breaks was observed with the combination of GNP/DTX vs GNP alone after a dose of 2 Gy was administered. In vivo results displayed significant reduction in tumor growth over a 30-day observation period with the treatment of GNP/DTX/RT when compared to GNP/RT after a single 5 Gy dose was given to mice. The treatment strategy also resulted in 100% mice survival, which was not observed for other treatment conditions. CONCLUSIONS: Incorporating DTX to work in unison with GNPs and RT can increase the efficacy of RT treatment. Our study suggests that the treatment strategy could improve tumor control through local dose enhancement. As the concentrations used in this study are clinically feasible, there is potential for this strategy to be translated into clinical settings. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12645-023-00228-0. |
format | Online Article Text |
id | pubmed-10539438 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Springer Vienna |
record_format | MEDLINE/PubMed |
spelling | pubmed-105394382023-09-30 Dual enhancement in the radiosensitivity of prostate cancer through nanoparticles and chemotherapeutics Jackson, Nolan Hill, Iona Alhussan, Abdulaziz Bromma, Kyle Morgan, Jessica Abousaida, Belal Zahra, Yasmin Mackeyev, Yuri Beckham, Wayne Herchko, Steven Krishnan, Sunil Chithrani, Devika Basnagge Cancer Nanotechnol Research BACKGROUND: Radiotherapy (RT) is an essential component in the treatment regimens for many cancer patients. However, the dose escalation required to improve curative results is hindered due to the normal tissue toxicity that is induced. The introduction of radiosensitizers to RT treatment is an avenue that is currently being explored to overcome this issue. By introducing radiosensitizers into tumor sites, it is possible to preferentially enhance the local dose deposited. Gold nanoparticles (GNPs) are a potential candidate that have shown great promise in increasing the radiosensitivity of cancer cells through an enhancement in DNA damage. Furthermore, docetaxel (DTX) is a chemotherapeutic agent that arrests cells in the G2/M phase of the cell cycle, the phase most sensitive to radiation damage. We hypothesized that by incorporating DTX to GNP-enhanced radiotherapy treatment, we could further improve the radiosensitization experienced by cancer cells. To assess this strategy, we analyzed the radiotherapeutic effects on monolayer cell cultures in vitro, as well as on a mice prostate xenograft model in vivo while using clinically feasible concentrations for both GNPs and DTX. RESULTS: The introduction of DTX to GNP-enhanced radiotherapy further increased the radiotherapeutic effects experienced by cancer cells. A 38% increase in DNA double-strand breaks was observed with the combination of GNP/DTX vs GNP alone after a dose of 2 Gy was administered. In vivo results displayed significant reduction in tumor growth over a 30-day observation period with the treatment of GNP/DTX/RT when compared to GNP/RT after a single 5 Gy dose was given to mice. The treatment strategy also resulted in 100% mice survival, which was not observed for other treatment conditions. CONCLUSIONS: Incorporating DTX to work in unison with GNPs and RT can increase the efficacy of RT treatment. Our study suggests that the treatment strategy could improve tumor control through local dose enhancement. As the concentrations used in this study are clinically feasible, there is potential for this strategy to be translated into clinical settings. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12645-023-00228-0. Springer Vienna 2023-09-29 2023 /pmc/articles/PMC10539438/ /pubmed/37781236 http://dx.doi.org/10.1186/s12645-023-00228-0 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Research Jackson, Nolan Hill, Iona Alhussan, Abdulaziz Bromma, Kyle Morgan, Jessica Abousaida, Belal Zahra, Yasmin Mackeyev, Yuri Beckham, Wayne Herchko, Steven Krishnan, Sunil Chithrani, Devika Basnagge Dual enhancement in the radiosensitivity of prostate cancer through nanoparticles and chemotherapeutics |
title | Dual enhancement in the radiosensitivity of prostate cancer through nanoparticles and chemotherapeutics |
title_full | Dual enhancement in the radiosensitivity of prostate cancer through nanoparticles and chemotherapeutics |
title_fullStr | Dual enhancement in the radiosensitivity of prostate cancer through nanoparticles and chemotherapeutics |
title_full_unstemmed | Dual enhancement in the radiosensitivity of prostate cancer through nanoparticles and chemotherapeutics |
title_short | Dual enhancement in the radiosensitivity of prostate cancer through nanoparticles and chemotherapeutics |
title_sort | dual enhancement in the radiosensitivity of prostate cancer through nanoparticles and chemotherapeutics |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10539438/ https://www.ncbi.nlm.nih.gov/pubmed/37781236 http://dx.doi.org/10.1186/s12645-023-00228-0 |
work_keys_str_mv | AT jacksonnolan dualenhancementintheradiosensitivityofprostatecancerthroughnanoparticlesandchemotherapeutics AT hilliona dualenhancementintheradiosensitivityofprostatecancerthroughnanoparticlesandchemotherapeutics AT alhussanabdulaziz dualenhancementintheradiosensitivityofprostatecancerthroughnanoparticlesandchemotherapeutics AT brommakyle dualenhancementintheradiosensitivityofprostatecancerthroughnanoparticlesandchemotherapeutics AT morganjessica dualenhancementintheradiosensitivityofprostatecancerthroughnanoparticlesandchemotherapeutics AT abousaidabelal dualenhancementintheradiosensitivityofprostatecancerthroughnanoparticlesandchemotherapeutics AT zahrayasmin dualenhancementintheradiosensitivityofprostatecancerthroughnanoparticlesandchemotherapeutics AT mackeyevyuri dualenhancementintheradiosensitivityofprostatecancerthroughnanoparticlesandchemotherapeutics AT beckhamwayne dualenhancementintheradiosensitivityofprostatecancerthroughnanoparticlesandchemotherapeutics AT herchkosteven dualenhancementintheradiosensitivityofprostatecancerthroughnanoparticlesandchemotherapeutics AT krishnansunil dualenhancementintheradiosensitivityofprostatecancerthroughnanoparticlesandchemotherapeutics AT chithranidevikabasnagge dualenhancementintheradiosensitivityofprostatecancerthroughnanoparticlesandchemotherapeutics |