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Glycyrrhetinic Acid-Functionalized Mesoporous Silica Nanoparticles for the Co-Delivery of DOX/CPT-PEG for Targeting HepG2 Cells
A pH-triggered mesoporous silica nanoparticle (MSN)-based nano-vehicle for the dual delivery of doxorubicin (DOX)/camptothecin-PEG (CPT-PEG) has been prepared. To enhance its selectivity, the nanoparticles were decorated with glycyrrhetinic acid (GA) to target HepG2 cells. The highly insoluble CPT w...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7694026/ https://www.ncbi.nlm.nih.gov/pubmed/33147860 http://dx.doi.org/10.3390/pharmaceutics12111048 |
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author | Martínez-Edo, Gabriel Fornaguera, Cristina Borrós, Salvador Sánchez-García, David |
author_facet | Martínez-Edo, Gabriel Fornaguera, Cristina Borrós, Salvador Sánchez-García, David |
author_sort | Martínez-Edo, Gabriel |
collection | PubMed |
description | A pH-triggered mesoporous silica nanoparticle (MSN)-based nano-vehicle for the dual delivery of doxorubicin (DOX)/camptothecin-PEG (CPT-PEG) has been prepared. To enhance its selectivity, the nanoparticles were decorated with glycyrrhetinic acid (GA) to target HepG2 cells. The highly insoluble CPT was derivatized with a reductive-cleavable PEG chain to improve its loading within the MSN. The preparation of these particles consisted of four steps. First, CPT-PEG was loaded within the pores of the MSN. Then, dihydrazide polyethylene glycol chains were introduced onto the surface of an aldehyde-functionalized MSN by means of a hydrazone bond. Afterwards, DOX was covalently attached to the other end of the dihydrazide polyethylene glycol chains. Finally, the resulting nanoparticles were decorated with GA by formation of an imine bond between the amino group of DOX and a benzaldehyde-GA derivative. The system was stable at physiological conditions and the release of both drugs was negligible. However, at acidic pH, a burst release of DOX and a gradual release of CPT-PEG takes place. GA-decorated drug delivery systems (DDS) selectively internalizes into HepG2. In vitro tests demonstrated that this system shows a great cytotoxicity towards HepG2 cells. Furthermore, glutathione cleavage of CPT prodrug assures the formation of free CPT leading to a synergistic effect in combination with DOX. |
format | Online Article Text |
id | pubmed-7694026 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-76940262020-11-28 Glycyrrhetinic Acid-Functionalized Mesoporous Silica Nanoparticles for the Co-Delivery of DOX/CPT-PEG for Targeting HepG2 Cells Martínez-Edo, Gabriel Fornaguera, Cristina Borrós, Salvador Sánchez-García, David Pharmaceutics Article A pH-triggered mesoporous silica nanoparticle (MSN)-based nano-vehicle for the dual delivery of doxorubicin (DOX)/camptothecin-PEG (CPT-PEG) has been prepared. To enhance its selectivity, the nanoparticles were decorated with glycyrrhetinic acid (GA) to target HepG2 cells. The highly insoluble CPT was derivatized with a reductive-cleavable PEG chain to improve its loading within the MSN. The preparation of these particles consisted of four steps. First, CPT-PEG was loaded within the pores of the MSN. Then, dihydrazide polyethylene glycol chains were introduced onto the surface of an aldehyde-functionalized MSN by means of a hydrazone bond. Afterwards, DOX was covalently attached to the other end of the dihydrazide polyethylene glycol chains. Finally, the resulting nanoparticles were decorated with GA by formation of an imine bond between the amino group of DOX and a benzaldehyde-GA derivative. The system was stable at physiological conditions and the release of both drugs was negligible. However, at acidic pH, a burst release of DOX and a gradual release of CPT-PEG takes place. GA-decorated drug delivery systems (DDS) selectively internalizes into HepG2. In vitro tests demonstrated that this system shows a great cytotoxicity towards HepG2 cells. Furthermore, glutathione cleavage of CPT prodrug assures the formation of free CPT leading to a synergistic effect in combination with DOX. MDPI 2020-11-02 /pmc/articles/PMC7694026/ /pubmed/33147860 http://dx.doi.org/10.3390/pharmaceutics12111048 Text en © 2020 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 Martínez-Edo, Gabriel Fornaguera, Cristina Borrós, Salvador Sánchez-García, David Glycyrrhetinic Acid-Functionalized Mesoporous Silica Nanoparticles for the Co-Delivery of DOX/CPT-PEG for Targeting HepG2 Cells |
title | Glycyrrhetinic Acid-Functionalized Mesoporous Silica Nanoparticles for the Co-Delivery of DOX/CPT-PEG for Targeting HepG2 Cells |
title_full | Glycyrrhetinic Acid-Functionalized Mesoporous Silica Nanoparticles for the Co-Delivery of DOX/CPT-PEG for Targeting HepG2 Cells |
title_fullStr | Glycyrrhetinic Acid-Functionalized Mesoporous Silica Nanoparticles for the Co-Delivery of DOX/CPT-PEG for Targeting HepG2 Cells |
title_full_unstemmed | Glycyrrhetinic Acid-Functionalized Mesoporous Silica Nanoparticles for the Co-Delivery of DOX/CPT-PEG for Targeting HepG2 Cells |
title_short | Glycyrrhetinic Acid-Functionalized Mesoporous Silica Nanoparticles for the Co-Delivery of DOX/CPT-PEG for Targeting HepG2 Cells |
title_sort | glycyrrhetinic acid-functionalized mesoporous silica nanoparticles for the co-delivery of dox/cpt-peg for targeting hepg2 cells |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7694026/ https://www.ncbi.nlm.nih.gov/pubmed/33147860 http://dx.doi.org/10.3390/pharmaceutics12111048 |
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