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Prostate-specific membrane antigen targeted gold nanoparticles for prostate cancer radiotherapy: does size matter for targeted particles?
Since the introduction of PSA testing, significantly more men have been diagnosed and treated for prostate cancer. Localized prostate cancer typically is treated with prostatectomy, however there is still a high risk of recurrence after surgery, and adjuvant radiation has been shown to mitigate dise...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Royal Society of Chemistry
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6764472/ https://www.ncbi.nlm.nih.gov/pubmed/31588336 http://dx.doi.org/10.1039/c9sc02290b |
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author | Luo, Dong Wang, Xinning Zeng, Sophia Ramamurthy, Gopalakrishnan Burda, Clemens Basilion, James P. |
author_facet | Luo, Dong Wang, Xinning Zeng, Sophia Ramamurthy, Gopalakrishnan Burda, Clemens Basilion, James P. |
author_sort | Luo, Dong |
collection | PubMed |
description | Since the introduction of PSA testing, significantly more men have been diagnosed and treated for prostate cancer. Localized prostate cancer typically is treated with prostatectomy, however there is still a high risk of recurrence after surgery, and adjuvant radiation has been shown to mitigate disease progression. X-ray therapy is frequently used as an adjuvant to treat prostate cancer, but is an imperfect tool. In this report we describe the development of a targeted-radiosensitizing nanoparticle that significantly improves X-ray therapy. Taking advantage of the demonstrated radiosensitizing activity of gold nanoparticles (AuNPs) we developed targeted AuNPs and varied both surface ligand density and AuNP size to develop an optimized AuNP for X-ray radiotherapy. We conjugated a prostate-specific membrane antigen (PSMA) targeting ligand, PSMA-1, to AuNPs and found that the targeting ligand dramatically improved gold uptake by PSMA-expressing PC3pip cells compared with PC3flu cells lacking the PSMA receptors. Further, enhancement of radiotherapy was significantly more pronounced by internalization of smaller PSMA targeted-AuNPs. Our studies provide a foundation for design of size-selected AuNPs for targeted radiotherapy and, for the first time, systematically investigate both the effect of ligand and AuNP size on the cell uptake, tumor targeting and radiotherapy efficacy. |
format | Online Article Text |
id | pubmed-6764472 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Royal Society of Chemistry |
record_format | MEDLINE/PubMed |
spelling | pubmed-67644722019-10-04 Prostate-specific membrane antigen targeted gold nanoparticles for prostate cancer radiotherapy: does size matter for targeted particles? Luo, Dong Wang, Xinning Zeng, Sophia Ramamurthy, Gopalakrishnan Burda, Clemens Basilion, James P. Chem Sci Chemistry Since the introduction of PSA testing, significantly more men have been diagnosed and treated for prostate cancer. Localized prostate cancer typically is treated with prostatectomy, however there is still a high risk of recurrence after surgery, and adjuvant radiation has been shown to mitigate disease progression. X-ray therapy is frequently used as an adjuvant to treat prostate cancer, but is an imperfect tool. In this report we describe the development of a targeted-radiosensitizing nanoparticle that significantly improves X-ray therapy. Taking advantage of the demonstrated radiosensitizing activity of gold nanoparticles (AuNPs) we developed targeted AuNPs and varied both surface ligand density and AuNP size to develop an optimized AuNP for X-ray radiotherapy. We conjugated a prostate-specific membrane antigen (PSMA) targeting ligand, PSMA-1, to AuNPs and found that the targeting ligand dramatically improved gold uptake by PSMA-expressing PC3pip cells compared with PC3flu cells lacking the PSMA receptors. Further, enhancement of radiotherapy was significantly more pronounced by internalization of smaller PSMA targeted-AuNPs. Our studies provide a foundation for design of size-selected AuNPs for targeted radiotherapy and, for the first time, systematically investigate both the effect of ligand and AuNP size on the cell uptake, tumor targeting and radiotherapy efficacy. Royal Society of Chemistry 2019-07-18 /pmc/articles/PMC6764472/ /pubmed/31588336 http://dx.doi.org/10.1039/c9sc02290b Text en This journal is © The Royal Society of Chemistry 2019 http://creativecommons.org/licenses/by/3.0/ This article is freely available. This article is licensed under a Creative Commons Attribution 3.0 Unported Licence (CC BY 3.0) |
spellingShingle | Chemistry Luo, Dong Wang, Xinning Zeng, Sophia Ramamurthy, Gopalakrishnan Burda, Clemens Basilion, James P. Prostate-specific membrane antigen targeted gold nanoparticles for prostate cancer radiotherapy: does size matter for targeted particles? |
title | Prostate-specific membrane antigen targeted gold nanoparticles for prostate cancer radiotherapy: does size matter for targeted particles?
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title_full | Prostate-specific membrane antigen targeted gold nanoparticles for prostate cancer radiotherapy: does size matter for targeted particles?
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title_fullStr | Prostate-specific membrane antigen targeted gold nanoparticles for prostate cancer radiotherapy: does size matter for targeted particles?
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title_full_unstemmed | Prostate-specific membrane antigen targeted gold nanoparticles for prostate cancer radiotherapy: does size matter for targeted particles?
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title_short | Prostate-specific membrane antigen targeted gold nanoparticles for prostate cancer radiotherapy: does size matter for targeted particles?
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title_sort | prostate-specific membrane antigen targeted gold nanoparticles for prostate cancer radiotherapy: does size matter for targeted particles? |
topic | Chemistry |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6764472/ https://www.ncbi.nlm.nih.gov/pubmed/31588336 http://dx.doi.org/10.1039/c9sc02290b |
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