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2-Hydroxyoleic acid-inserted liposomes as a multifunctional carrier of anticancer drugs
Studies have shown that insertion of oleic acid into lipid bilayers can modulate the membrane properties of liposomes so as to improve their function as drug carriers. Considering that 2-hydroxyoleic acid (2OHOA), a potential antitumor agent currently undergoing clinical trials, is a derivative of o...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Taylor & Francis
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8241020/ https://www.ncbi.nlm.nih.gov/pubmed/29029595 http://dx.doi.org/10.1080/10717544.2017.1388452 |
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author | Jang, Eun-Ji Choi, Woo Rim Kim, Soo-Yeon Hong, Soon-Seok Rhee, Inmoo Lee, Sang-Jin Choi, Sung Weon Choi, Han-Gon Lim, Soo-Jeong |
author_facet | Jang, Eun-Ji Choi, Woo Rim Kim, Soo-Yeon Hong, Soon-Seok Rhee, Inmoo Lee, Sang-Jin Choi, Sung Weon Choi, Han-Gon Lim, Soo-Jeong |
author_sort | Jang, Eun-Ji |
collection | PubMed |
description | Studies have shown that insertion of oleic acid into lipid bilayers can modulate the membrane properties of liposomes so as to improve their function as drug carriers. Considering that 2-hydroxyoleic acid (2OHOA), a potential antitumor agent currently undergoing clinical trials, is a derivative of oleic acid, we explored the possibility of developing 2OHOA-inserted liposomes as a multifunctional carrier of antitumor drugs in the present study. The insertion of 2OHOA into lipid bilayers was confirmed by surface charge determination and differential scanning calorimetry. 2OHOA insertion greatly decreased the order of dimyristoylphosphatidylcholine packing, produced a nanosized (<100 nm) dispersion, and improved the colloidal stability of liposomes during storage. Moreover, 2OHOA-inserted liposome forms exhibited greater growth inhibitory activity against cancer cells compared with free 2OHOA, and the growth-inhibitory activity of liposomal 2OHOA was selective for tumor cells. 2OHOA insertion greatly increased the liposome-incorporated concentration of hydrophobic model drugs, including mitoxantrone, paclitaxel, and all-trans retinoic acid (ATRA). The in vitro anticancer activity of ATRA-incorporated/2OHOA-inserted liposomes was significantly higher than that of ATRA-incorporated conventional liposomes. In a B16-F10 melanoma syngeneic mouse model, the tumor growth rate was significantly delayed in mice treated with ATRA-incorporated/2OHOA-inserted liposomes compared with that in the control group. Immunohistochemical analyses revealed that the enhanced antitumor activity of ATRA-incorporated/2OHOA-inserted liposomes was due, at least in part, to increased induction of apoptosis. Collectively, our findings indicate that 2OHOA-inserted liposomes exhibit multiple advantages as antitumor drug carriers, including the ability to simultaneously deliver two anticancer drugs – 2OHOA and incorporated drug – to the tumor tissue. |
format | Online Article Text |
id | pubmed-8241020 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Taylor & Francis |
record_format | MEDLINE/PubMed |
spelling | pubmed-82410202021-07-08 2-Hydroxyoleic acid-inserted liposomes as a multifunctional carrier of anticancer drugs Jang, Eun-Ji Choi, Woo Rim Kim, Soo-Yeon Hong, Soon-Seok Rhee, Inmoo Lee, Sang-Jin Choi, Sung Weon Choi, Han-Gon Lim, Soo-Jeong Drug Deliv Research Article Studies have shown that insertion of oleic acid into lipid bilayers can modulate the membrane properties of liposomes so as to improve their function as drug carriers. Considering that 2-hydroxyoleic acid (2OHOA), a potential antitumor agent currently undergoing clinical trials, is a derivative of oleic acid, we explored the possibility of developing 2OHOA-inserted liposomes as a multifunctional carrier of antitumor drugs in the present study. The insertion of 2OHOA into lipid bilayers was confirmed by surface charge determination and differential scanning calorimetry. 2OHOA insertion greatly decreased the order of dimyristoylphosphatidylcholine packing, produced a nanosized (<100 nm) dispersion, and improved the colloidal stability of liposomes during storage. Moreover, 2OHOA-inserted liposome forms exhibited greater growth inhibitory activity against cancer cells compared with free 2OHOA, and the growth-inhibitory activity of liposomal 2OHOA was selective for tumor cells. 2OHOA insertion greatly increased the liposome-incorporated concentration of hydrophobic model drugs, including mitoxantrone, paclitaxel, and all-trans retinoic acid (ATRA). The in vitro anticancer activity of ATRA-incorporated/2OHOA-inserted liposomes was significantly higher than that of ATRA-incorporated conventional liposomes. In a B16-F10 melanoma syngeneic mouse model, the tumor growth rate was significantly delayed in mice treated with ATRA-incorporated/2OHOA-inserted liposomes compared with that in the control group. Immunohistochemical analyses revealed that the enhanced antitumor activity of ATRA-incorporated/2OHOA-inserted liposomes was due, at least in part, to increased induction of apoptosis. Collectively, our findings indicate that 2OHOA-inserted liposomes exhibit multiple advantages as antitumor drug carriers, including the ability to simultaneously deliver two anticancer drugs – 2OHOA and incorporated drug – to the tumor tissue. Taylor & Francis 2017-10-13 /pmc/articles/PMC8241020/ /pubmed/29029595 http://dx.doi.org/10.1080/10717544.2017.1388452 Text en © 2017 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Article Jang, Eun-Ji Choi, Woo Rim Kim, Soo-Yeon Hong, Soon-Seok Rhee, Inmoo Lee, Sang-Jin Choi, Sung Weon Choi, Han-Gon Lim, Soo-Jeong 2-Hydroxyoleic acid-inserted liposomes as a multifunctional carrier of anticancer drugs |
title | 2-Hydroxyoleic acid-inserted liposomes as a multifunctional carrier of anticancer drugs |
title_full | 2-Hydroxyoleic acid-inserted liposomes as a multifunctional carrier of anticancer drugs |
title_fullStr | 2-Hydroxyoleic acid-inserted liposomes as a multifunctional carrier of anticancer drugs |
title_full_unstemmed | 2-Hydroxyoleic acid-inserted liposomes as a multifunctional carrier of anticancer drugs |
title_short | 2-Hydroxyoleic acid-inserted liposomes as a multifunctional carrier of anticancer drugs |
title_sort | 2-hydroxyoleic acid-inserted liposomes as a multifunctional carrier of anticancer drugs |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8241020/ https://www.ncbi.nlm.nih.gov/pubmed/29029595 http://dx.doi.org/10.1080/10717544.2017.1388452 |
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