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Aptamer-functionalized Hybrid Nanoparticles to Enhance the Delivery of Doxorubicin into Breast Cancer Cells by Silencing P-glycoprotein
OBJECTIVE: The MDR of metastatic breast cancer cells is accompanied by the overexpression of P-gp transporter. This study has been focused to determine whether silencing the expression of P-gp by aptamer-labeled siRNA nanoparticles could enhance the delivery of doxorubicin into breast cancer cells i...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7213597/ https://www.ncbi.nlm.nih.gov/pubmed/32395707 http://dx.doi.org/10.29245/2578-2967/2020/1.1176 |
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author | Chandra, Sruti Michael Nguyen, Hoang Wiltz, Kylar Hall, Nicholas Chaudhry, Shanzay Olverson, George Mandal, Tarun Dash, Srikanta Kundu, Anup |
author_facet | Chandra, Sruti Michael Nguyen, Hoang Wiltz, Kylar Hall, Nicholas Chaudhry, Shanzay Olverson, George Mandal, Tarun Dash, Srikanta Kundu, Anup |
author_sort | Chandra, Sruti |
collection | PubMed |
description | OBJECTIVE: The MDR of metastatic breast cancer cells is accompanied by the overexpression of P-gp transporter. This study has been focused to determine whether silencing the expression of P-gp by aptamer-labeled siRNA nanoparticles could enhance the delivery of doxorubicin into breast cancer cells in culture. METHODOLOGY: The nanoparticle F-31 was prepared using DOTAP, cholesterol, and PLGA, and then incorporating Mal-PEG to facilitate aptamer-binding. The nanoparticles were surface-functionalized with aptamer A6, which targets Her-2 receptors overexpressed on the surface of breast cancer cells. RESULTS: This study has shown that the uptake of Dox by Dox-resistant 4T1-R is significantly less than Dox-sensitive 4T1-S which is partly attributed to the higher expression of drug-efflux pump P-gp on the surface of the resistant cells. The targeted knockdown of P-gp has been enhanced when the particles carrying P-gp siRNA was labeled with aptamer. Concurrently, the uptake of Dox into the Dox-resistant 4T1-R breast cancer cells has increased significantly when the P-gp was silenced by P-gp siRNA-encapsulated aptamer-labeled nanoparticles. CONCLUSIONS: This preliminary study concludes that downregulating P-gp expression by targeted delivery of P-gp siRNA using aptamer-labeled lipid-based hybrid nanoparticles could effectively increase the intracellular trafficking of doxorubicin in Dox-resistant mouse breast cancer cells. |
format | Online Article Text |
id | pubmed-7213597 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
record_format | MEDLINE/PubMed |
spelling | pubmed-72135972020-05-11 Aptamer-functionalized Hybrid Nanoparticles to Enhance the Delivery of Doxorubicin into Breast Cancer Cells by Silencing P-glycoprotein Chandra, Sruti Michael Nguyen, Hoang Wiltz, Kylar Hall, Nicholas Chaudhry, Shanzay Olverson, George Mandal, Tarun Dash, Srikanta Kundu, Anup J Cancer Treatment Diagn Article OBJECTIVE: The MDR of metastatic breast cancer cells is accompanied by the overexpression of P-gp transporter. This study has been focused to determine whether silencing the expression of P-gp by aptamer-labeled siRNA nanoparticles could enhance the delivery of doxorubicin into breast cancer cells in culture. METHODOLOGY: The nanoparticle F-31 was prepared using DOTAP, cholesterol, and PLGA, and then incorporating Mal-PEG to facilitate aptamer-binding. The nanoparticles were surface-functionalized with aptamer A6, which targets Her-2 receptors overexpressed on the surface of breast cancer cells. RESULTS: This study has shown that the uptake of Dox by Dox-resistant 4T1-R is significantly less than Dox-sensitive 4T1-S which is partly attributed to the higher expression of drug-efflux pump P-gp on the surface of the resistant cells. The targeted knockdown of P-gp has been enhanced when the particles carrying P-gp siRNA was labeled with aptamer. Concurrently, the uptake of Dox into the Dox-resistant 4T1-R breast cancer cells has increased significantly when the P-gp was silenced by P-gp siRNA-encapsulated aptamer-labeled nanoparticles. CONCLUSIONS: This preliminary study concludes that downregulating P-gp expression by targeted delivery of P-gp siRNA using aptamer-labeled lipid-based hybrid nanoparticles could effectively increase the intracellular trafficking of doxorubicin in Dox-resistant mouse breast cancer cells. 2020 /pmc/articles/PMC7213597/ /pubmed/32395707 http://dx.doi.org/10.29245/2578-2967/2020/1.1176 Text en http://creativecommons.org/licenses/by/4.0/ This article is distributed under the terms of the Creative Commons Attribution 4.0 International License. |
spellingShingle | Article Chandra, Sruti Michael Nguyen, Hoang Wiltz, Kylar Hall, Nicholas Chaudhry, Shanzay Olverson, George Mandal, Tarun Dash, Srikanta Kundu, Anup Aptamer-functionalized Hybrid Nanoparticles to Enhance the Delivery of Doxorubicin into Breast Cancer Cells by Silencing P-glycoprotein |
title | Aptamer-functionalized Hybrid Nanoparticles to Enhance the Delivery of Doxorubicin into Breast Cancer Cells by Silencing P-glycoprotein |
title_full | Aptamer-functionalized Hybrid Nanoparticles to Enhance the Delivery of Doxorubicin into Breast Cancer Cells by Silencing P-glycoprotein |
title_fullStr | Aptamer-functionalized Hybrid Nanoparticles to Enhance the Delivery of Doxorubicin into Breast Cancer Cells by Silencing P-glycoprotein |
title_full_unstemmed | Aptamer-functionalized Hybrid Nanoparticles to Enhance the Delivery of Doxorubicin into Breast Cancer Cells by Silencing P-glycoprotein |
title_short | Aptamer-functionalized Hybrid Nanoparticles to Enhance the Delivery of Doxorubicin into Breast Cancer Cells by Silencing P-glycoprotein |
title_sort | aptamer-functionalized hybrid nanoparticles to enhance the delivery of doxorubicin into breast cancer cells by silencing p-glycoprotein |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7213597/ https://www.ncbi.nlm.nih.gov/pubmed/32395707 http://dx.doi.org/10.29245/2578-2967/2020/1.1176 |
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