Enzyme-responsive doxorubicin release from dendrimer nanoparticles for anticancer drug delivery

Sang Joon Lee,1,* Young-Il Jeong,2,* Hyung-Kyu Park,3 Dae Hwan Kang,2,4 Jong-Suk Oh,3 Sam-Gyu Lee,5 Hyun Chul Lee31Department of Biomedical Sciences, Chonnam National University Medical School, Gwangju, 2Biomedical Research Institute, Pusan National University Hospital, Busan, 3Department of Microbi...

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Autores principales:	Lee SJ, Jeong YI, Park HK, Kang DH, Oh JS, Lee SG, Lee HC
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2015
Materias:	Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/283c8539a2df43d7ab6a298a45944c66
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spelling	oai:doaj.org-article:283c8539a2df43d7ab6a298a45944c662021-12-02T02:29:09ZEnzyme-responsive doxorubicin release from dendrimer nanoparticles for anticancer drug delivery1178-2013https://doaj.org/article/283c8539a2df43d7ab6a298a45944c662015-08-01T00:00:00Zhttp://www.dovepress.com/enzyme-responsive-doxorubicin-release-from-dendrimer-nanoparticles-for-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Sang Joon Lee,1,* Young-Il Jeong,2,* Hyung-Kyu Park,3 Dae Hwan Kang,2,4 Jong-Suk Oh,3 Sam-Gyu Lee,5 Hyun Chul Lee31Department of Biomedical Sciences, Chonnam National University Medical School, Gwangju, 2Biomedical Research Institute, Pusan National University Hospital, Busan, 3Department of Microbiology, Chonnam National University Medical School, Gwangju, 4Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Gyeongnam, 5Department of Physical and Rehabilitation Medicine, Chonnam National University Medical School, Gwangju, Republic of Korea*These authors contributed equally to this workBackground: Since cancer cells are normally over-expressed cathepsin B, we synthesized dendrimer-methoxy poly(ethylene glycol) (MPEG)-doxorubicin (DOX) conjugates using a cathepsin B-cleavable peptide for anticancer drug targeting.Methods: Gly-Phe-Leu-Gly peptide was conjugated with the carboxylic acid end groups of a dendrimer, which was then conjugated with MPEG amine and doxorubicin by aid of carbodiimide chemistry (abbreviated as DendGDP). Dendrimer-MPEG-DOX conjugates without Gly-Phe-Leu-Gly peptide linkage was also synthesized for comparison (DendDP). Nanoparticles were then prepared using a dialysis procedure.Results: The synthesized DendGDP was confirmed with 1H nuclear magnetic resonance spectroscopy. The DendDP and DendGDP nanoparticles had a small particle size of less than 200 nm and had a spherical morphology. DendGDP had cathepsin B-sensitive drug release properties while DendDP did not show cathepsin B sensitivity. Further, DendGDP had improved anticancer activity when compared with doxorubicin or DendDP in an in vivo CT26 tumor xenograft model, ie, the volume of the CT26 tumor xenograft was significantly inhibited when compared with xenografts treated with doxorubicin or DendDP nanoparticles. The DendGDP nanoparticles were found to be relatively concentrated in the tumor tissue and revealed stronger fluorescence intensity than at other body sites while doxorubicin and DendDP nanoparticles showed strong fluorescence intensity in the various organs, indicating that DendGDP has cathepsin B sensitivity.Conclusion: DendGDP is sensitive to cathepsin B in tumor cells and can be used as a cathepsin B-responsive drug targeting strategy. We suggest that DendGDP is a promising vehicle for cancer cell targeting.Keywords: cathepsin B, CT26 cell, enzyme-sensitive dendrimer, tumor targeting, tetra peptideLee SJJeong YIPark HKKang DHOh JSLee SGLee HCDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2015, Iss default, Pp 5489-5503 (2015)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine (General) R5-920
spellingShingle	Medicine (General) R5-920 Lee SJ Jeong YI Park HK Kang DH Oh JS Lee SG Lee HC Enzyme-responsive doxorubicin release from dendrimer nanoparticles for anticancer drug delivery
description	Sang Joon Lee,1,* Young-Il Jeong,2,* Hyung-Kyu Park,3 Dae Hwan Kang,2,4 Jong-Suk Oh,3 Sam-Gyu Lee,5 Hyun Chul Lee31Department of Biomedical Sciences, Chonnam National University Medical School, Gwangju, 2Biomedical Research Institute, Pusan National University Hospital, Busan, 3Department of Microbiology, Chonnam National University Medical School, Gwangju, 4Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Gyeongnam, 5Department of Physical and Rehabilitation Medicine, Chonnam National University Medical School, Gwangju, Republic of Korea*These authors contributed equally to this workBackground: Since cancer cells are normally over-expressed cathepsin B, we synthesized dendrimer-methoxy poly(ethylene glycol) (MPEG)-doxorubicin (DOX) conjugates using a cathepsin B-cleavable peptide for anticancer drug targeting.Methods: Gly-Phe-Leu-Gly peptide was conjugated with the carboxylic acid end groups of a dendrimer, which was then conjugated with MPEG amine and doxorubicin by aid of carbodiimide chemistry (abbreviated as DendGDP). Dendrimer-MPEG-DOX conjugates without Gly-Phe-Leu-Gly peptide linkage was also synthesized for comparison (DendDP). Nanoparticles were then prepared using a dialysis procedure.Results: The synthesized DendGDP was confirmed with 1H nuclear magnetic resonance spectroscopy. The DendDP and DendGDP nanoparticles had a small particle size of less than 200 nm and had a spherical morphology. DendGDP had cathepsin B-sensitive drug release properties while DendDP did not show cathepsin B sensitivity. Further, DendGDP had improved anticancer activity when compared with doxorubicin or DendDP in an in vivo CT26 tumor xenograft model, ie, the volume of the CT26 tumor xenograft was significantly inhibited when compared with xenografts treated with doxorubicin or DendDP nanoparticles. The DendGDP nanoparticles were found to be relatively concentrated in the tumor tissue and revealed stronger fluorescence intensity than at other body sites while doxorubicin and DendDP nanoparticles showed strong fluorescence intensity in the various organs, indicating that DendGDP has cathepsin B sensitivity.Conclusion: DendGDP is sensitive to cathepsin B in tumor cells and can be used as a cathepsin B-responsive drug targeting strategy. We suggest that DendGDP is a promising vehicle for cancer cell targeting.Keywords: cathepsin B, CT26 cell, enzyme-sensitive dendrimer, tumor targeting, tetra peptide
format	article
author	Lee SJ Jeong YI Park HK Kang DH Oh JS Lee SG Lee HC
author_facet	Lee SJ Jeong YI Park HK Kang DH Oh JS Lee SG Lee HC
author_sort	Lee SJ
title	Enzyme-responsive doxorubicin release from dendrimer nanoparticles for anticancer drug delivery
title_short	Enzyme-responsive doxorubicin release from dendrimer nanoparticles for anticancer drug delivery
title_full	Enzyme-responsive doxorubicin release from dendrimer nanoparticles for anticancer drug delivery
title_fullStr	Enzyme-responsive doxorubicin release from dendrimer nanoparticles for anticancer drug delivery
title_full_unstemmed	Enzyme-responsive doxorubicin release from dendrimer nanoparticles for anticancer drug delivery
title_sort	enzyme-responsive doxorubicin release from dendrimer nanoparticles for anticancer drug delivery
publisher	Dove Medical Press
publishDate	2015
url	https://doaj.org/article/283c8539a2df43d7ab6a298a45944c66
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Enzyme-responsive doxorubicin release from dendrimer nanoparticles for anticancer drug delivery

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