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Citrate- and Succinate-Modified Carbonate Apatite Nanoparticles with Loaded Doxorubicin Exhibit Potent Anticancer Activity against Breast Cancer Cells

Biodegradable inorganic apatite-based particle complex is popular for its pH-sensitivity at the endosomal acidic environment to facilitate drug release following cellular uptake. Despite being a powerful anticancer drug, doxorubicin shows severe off-target effects and therefore would need a carrier...

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Autores principales: Mehbuba Hossain, Sultana, Chowdhury, Ezharul Hoque
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5874845/
https://www.ncbi.nlm.nih.gov/pubmed/29534497
http://dx.doi.org/10.3390/pharmaceutics10010032
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author Mehbuba Hossain, Sultana
Chowdhury, Ezharul Hoque
author_facet Mehbuba Hossain, Sultana
Chowdhury, Ezharul Hoque
author_sort Mehbuba Hossain, Sultana
collection PubMed
description Biodegradable inorganic apatite-based particle complex is popular for its pH-sensitivity at the endosomal acidic environment to facilitate drug release following cellular uptake. Despite being a powerful anticancer drug, doxorubicin shows severe off-target effects and therefore would need a carrier for the highest effectiveness. We aimed to chemically modify carbonate apatite (CA) with Krebs cycle intermediates, such as citrate and succinate in order to control the growth of the resultant particles to more efficiently carry and transport the anticancer drug into the cancer cells. Citrate- or succinate-modified CA particles were synthesized with different concentrations of sodium citrate or sodium succinate, respectively, in the absence or presence of doxorubicin. The drug loading efficiency of the particles and their cellular uptake were observed by quantifying fluorescence intensity. The average diameter and surface charge of the particles were determined using Zetasizer. Cell viability was assessed by MTT assay. Citrate-modified carbonate apatite (CMCA) exhibited the highest (31.38%) binding affinity for doxorubicin and promoted rapid cellular uptake of the drug, leading to the half-maximal inhibitory concentration 1000 times less than that of the free drug in MCF-7 cells. Hence, CMCA nanoparticles with greater surface area enhance cytotoxicity in different breast cancer cells by enabling higher loading and more efficient cellular uptake of the drug.
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spelling pubmed-58748452018-04-02 Citrate- and Succinate-Modified Carbonate Apatite Nanoparticles with Loaded Doxorubicin Exhibit Potent Anticancer Activity against Breast Cancer Cells Mehbuba Hossain, Sultana Chowdhury, Ezharul Hoque Pharmaceutics Article Biodegradable inorganic apatite-based particle complex is popular for its pH-sensitivity at the endosomal acidic environment to facilitate drug release following cellular uptake. Despite being a powerful anticancer drug, doxorubicin shows severe off-target effects and therefore would need a carrier for the highest effectiveness. We aimed to chemically modify carbonate apatite (CA) with Krebs cycle intermediates, such as citrate and succinate in order to control the growth of the resultant particles to more efficiently carry and transport the anticancer drug into the cancer cells. Citrate- or succinate-modified CA particles were synthesized with different concentrations of sodium citrate or sodium succinate, respectively, in the absence or presence of doxorubicin. The drug loading efficiency of the particles and their cellular uptake were observed by quantifying fluorescence intensity. The average diameter and surface charge of the particles were determined using Zetasizer. Cell viability was assessed by MTT assay. Citrate-modified carbonate apatite (CMCA) exhibited the highest (31.38%) binding affinity for doxorubicin and promoted rapid cellular uptake of the drug, leading to the half-maximal inhibitory concentration 1000 times less than that of the free drug in MCF-7 cells. Hence, CMCA nanoparticles with greater surface area enhance cytotoxicity in different breast cancer cells by enabling higher loading and more efficient cellular uptake of the drug. MDPI 2018-03-11 /pmc/articles/PMC5874845/ /pubmed/29534497 http://dx.doi.org/10.3390/pharmaceutics10010032 Text en © 2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Mehbuba Hossain, Sultana
Chowdhury, Ezharul Hoque
Citrate- and Succinate-Modified Carbonate Apatite Nanoparticles with Loaded Doxorubicin Exhibit Potent Anticancer Activity against Breast Cancer Cells
title Citrate- and Succinate-Modified Carbonate Apatite Nanoparticles with Loaded Doxorubicin Exhibit Potent Anticancer Activity against Breast Cancer Cells
title_full Citrate- and Succinate-Modified Carbonate Apatite Nanoparticles with Loaded Doxorubicin Exhibit Potent Anticancer Activity against Breast Cancer Cells
title_fullStr Citrate- and Succinate-Modified Carbonate Apatite Nanoparticles with Loaded Doxorubicin Exhibit Potent Anticancer Activity against Breast Cancer Cells
title_full_unstemmed Citrate- and Succinate-Modified Carbonate Apatite Nanoparticles with Loaded Doxorubicin Exhibit Potent Anticancer Activity against Breast Cancer Cells
title_short Citrate- and Succinate-Modified Carbonate Apatite Nanoparticles with Loaded Doxorubicin Exhibit Potent Anticancer Activity against Breast Cancer Cells
title_sort citrate- and succinate-modified carbonate apatite nanoparticles with loaded doxorubicin exhibit potent anticancer activity against breast cancer cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5874845/
https://www.ncbi.nlm.nih.gov/pubmed/29534497
http://dx.doi.org/10.3390/pharmaceutics10010032
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