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Prostate-Specific Membrane Antigen Targeted Polymersomes for Delivering Mocetinostat and Docetaxel to Prostate Cancer Cell Spheroids

[Image: see text] Prostate cancer cells overexpress the prostate-specific membrane antigen (PSMA) receptors on the surface. Targeting the PSMA receptor creates a unique opportunity for drug delivery. Docetaxel is a Food and Drug Administration-approved drug for treating metastatic and androgen-indep...

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Autores principales: Karandish, Fataneh, Haldar, Manas K., You, Seungyong, Brooks, Amanda E., Brooks, Benjamin D., Guo, Bin, Choi, Yongki, Mallik, Sanku
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2016
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5131327/
https://www.ncbi.nlm.nih.gov/pubmed/27917408
http://dx.doi.org/10.1021/acsomega.6b00126
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author Karandish, Fataneh
Haldar, Manas K.
You, Seungyong
Brooks, Amanda E.
Brooks, Benjamin D.
Guo, Bin
Choi, Yongki
Mallik, Sanku
author_facet Karandish, Fataneh
Haldar, Manas K.
You, Seungyong
Brooks, Amanda E.
Brooks, Benjamin D.
Guo, Bin
Choi, Yongki
Mallik, Sanku
author_sort Karandish, Fataneh
collection PubMed
description [Image: see text] Prostate cancer cells overexpress the prostate-specific membrane antigen (PSMA) receptors on the surface. Targeting the PSMA receptor creates a unique opportunity for drug delivery. Docetaxel is a Food and Drug Administration-approved drug for treating metastatic and androgen-independent prostate cancer, and mocetinostat is a potent inhibitor of class I histone deacetylases. In this study, we prepared reduction-sensitive polymersomes presenting folic acid on the surface and encapsulating either docetaxel or mocetinostat. The presence of folic acid allowed efficient targeting of the PSMA receptor and subsequent internalization of the polymeric vesicles in cultured LNCaP prostate cancer cell spheroids. The intracellular reducing agents efficiently released docetaxel and mocetinostat from the polymersomes. The combination of the two drug-encapsulated polymersome formulations significantly (p < 0.05) decreased the viability of the LNCaP cells (compared to free drugs or control) in three-dimensional spheroid cultures. The calculated combination index value indicated a synergistic effect for the combination of mocetinostat and docetaxel. Thus, our PSMA-targeted drug-encapsulated polymersomes has the potential to lead to a new direction in prostate cancer therapy that decreases the toxicity and increases the efficacy of the drug delivery systems.
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spelling pubmed-51313272016-12-02 Prostate-Specific Membrane Antigen Targeted Polymersomes for Delivering Mocetinostat and Docetaxel to Prostate Cancer Cell Spheroids Karandish, Fataneh Haldar, Manas K. You, Seungyong Brooks, Amanda E. Brooks, Benjamin D. Guo, Bin Choi, Yongki Mallik, Sanku ACS Omega [Image: see text] Prostate cancer cells overexpress the prostate-specific membrane antigen (PSMA) receptors on the surface. Targeting the PSMA receptor creates a unique opportunity for drug delivery. Docetaxel is a Food and Drug Administration-approved drug for treating metastatic and androgen-independent prostate cancer, and mocetinostat is a potent inhibitor of class I histone deacetylases. In this study, we prepared reduction-sensitive polymersomes presenting folic acid on the surface and encapsulating either docetaxel or mocetinostat. The presence of folic acid allowed efficient targeting of the PSMA receptor and subsequent internalization of the polymeric vesicles in cultured LNCaP prostate cancer cell spheroids. The intracellular reducing agents efficiently released docetaxel and mocetinostat from the polymersomes. The combination of the two drug-encapsulated polymersome formulations significantly (p < 0.05) decreased the viability of the LNCaP cells (compared to free drugs or control) in three-dimensional spheroid cultures. The calculated combination index value indicated a synergistic effect for the combination of mocetinostat and docetaxel. Thus, our PSMA-targeted drug-encapsulated polymersomes has the potential to lead to a new direction in prostate cancer therapy that decreases the toxicity and increases the efficacy of the drug delivery systems. American Chemical Society 2016-11-16 /pmc/articles/PMC5131327/ /pubmed/27917408 http://dx.doi.org/10.1021/acsomega.6b00126 Text en Copyright © 2016 American Chemical Society This is an open access article published under a Creative Commons Non-Commercial No Derivative Works (CC-BY-NC-ND) Attribution License (http://pubs.acs.org/page/policy/authorchoice_ccbyncnd_termsofuse.html) , which permits copying and redistribution of the article, and creation of adaptations, all for non-commercial purposes.
spellingShingle Karandish, Fataneh
Haldar, Manas K.
You, Seungyong
Brooks, Amanda E.
Brooks, Benjamin D.
Guo, Bin
Choi, Yongki
Mallik, Sanku
Prostate-Specific Membrane Antigen Targeted Polymersomes for Delivering Mocetinostat and Docetaxel to Prostate Cancer Cell Spheroids
title Prostate-Specific Membrane Antigen Targeted Polymersomes for Delivering Mocetinostat and Docetaxel to Prostate Cancer Cell Spheroids
title_full Prostate-Specific Membrane Antigen Targeted Polymersomes for Delivering Mocetinostat and Docetaxel to Prostate Cancer Cell Spheroids
title_fullStr Prostate-Specific Membrane Antigen Targeted Polymersomes for Delivering Mocetinostat and Docetaxel to Prostate Cancer Cell Spheroids
title_full_unstemmed Prostate-Specific Membrane Antigen Targeted Polymersomes for Delivering Mocetinostat and Docetaxel to Prostate Cancer Cell Spheroids
title_short Prostate-Specific Membrane Antigen Targeted Polymersomes for Delivering Mocetinostat and Docetaxel to Prostate Cancer Cell Spheroids
title_sort prostate-specific membrane antigen targeted polymersomes for delivering mocetinostat and docetaxel to prostate cancer cell spheroids
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5131327/
https://www.ncbi.nlm.nih.gov/pubmed/27917408
http://dx.doi.org/10.1021/acsomega.6b00126
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