Development and evaluation of pH-responsive single-walled carbon nanotube-doxorubicin complexes in cancer cells

Yan-Juan Gu1,2,*, Jinping Cheng2,*, Jiefu Jin3, Shuk Han Cheng2, Wing-Tak Wong11Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, 2Department of Biology and Chemistry, The City University of Hong Kong, 3Department of Chemistry, The University of Hong Kong,...

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Autores principales:	Gu YJ, Cheng J, Jin J, Cheng SH, Wong WT
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2011
Materias:	Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/5d07df47d667496194c04814673652c1
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spelling	oai:doaj.org-article:5d07df47d667496194c04814673652c12021-12-02T01:29:49ZDevelopment and evaluation of pH-responsive single-walled carbon nanotube-doxorubicin complexes in cancer cells1176-91141178-2013https://doaj.org/article/5d07df47d667496194c04814673652c12011-11-01T00:00:00Zhttp://www.dovepress.com/development-and-evaluation-of-ph-responsive-single-walled-carbon-nanot-a8680https://doaj.org/toc/1176-9114https://doaj.org/toc/1178-2013Yan-Juan Gu1,2,, Jinping Cheng2,, Jiefu Jin3, Shuk Han Cheng2, Wing-Tak Wong11Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, 2Department of Biology and Chemistry, The City University of Hong Kong, 3Department of Chemistry, The University of Hong Kong, Hong Kong, China*These authors contributed equally to this workAbstract: Single-walled carbon nanotubes (SWNTs) have been identified as an efficient drug carrier. Here a controlled drug-delivery system based on SWNTs coated with doxorubicin (DOX) through hydrazone bonds was developed, because the hydrazone bond is more sensitive to tumor microenvironments than other covalent linkers. The SWNTs were firstly stabilized with polyethylene glycol (H2N-PEG-NH2). Hydrazinobenzoic acid (HBA) was then covalently attached on SWNTs via carbodiimide-activated coupling reaction to form hydrazine-modified SWNTs. The anticancer drug DOX was conjugated to the HBA segments of SWNT using hydrazine as the linker. The resulting hydrazone bonds formed between the DOX molecules and the HBA segments of SWNTs are acid cleavable, thereby providing a strong pH-responsive drug release, which may facilitate effective DOX release near the acidic tumor microenvironment and thus reduce its overall systemic toxicity. The DOX-loaded SWNTs were efficiently taken up by HepG2 tumor cells, and DOX was released intracellularly, as revealed by MTT assay and confocal microscope observations. Compared with SWNT-DOX conjugate formed by supramolecular interaction, the SWNT-HBA-DOX featured high weight loading and prolonged release of DOX, and thus improved its cytotoxicity against cancer cells. This study suggests that while SWNTs have great potential as a drug carrier, the efficient formulation strategy requires further study.Keywords: carbon nanotubes, drug delivery, controlled release, SWNTsGu YJCheng JJin JCheng SHWong WTDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2011, Iss default, Pp 2889-2898 (2011)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine (General) R5-920
spellingShingle	Medicine (General) R5-920 Gu YJ Cheng J Jin J Cheng SH Wong WT Development and evaluation of pH-responsive single-walled carbon nanotube-doxorubicin complexes in cancer cells
description	Yan-Juan Gu1,2,, Jinping Cheng2,, Jiefu Jin3, Shuk Han Cheng2, Wing-Tak Wong11Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, 2Department of Biology and Chemistry, The City University of Hong Kong, 3Department of Chemistry, The University of Hong Kong, Hong Kong, China*These authors contributed equally to this workAbstract: Single-walled carbon nanotubes (SWNTs) have been identified as an efficient drug carrier. Here a controlled drug-delivery system based on SWNTs coated with doxorubicin (DOX) through hydrazone bonds was developed, because the hydrazone bond is more sensitive to tumor microenvironments than other covalent linkers. The SWNTs were firstly stabilized with polyethylene glycol (H2N-PEG-NH2). Hydrazinobenzoic acid (HBA) was then covalently attached on SWNTs via carbodiimide-activated coupling reaction to form hydrazine-modified SWNTs. The anticancer drug DOX was conjugated to the HBA segments of SWNT using hydrazine as the linker. The resulting hydrazone bonds formed between the DOX molecules and the HBA segments of SWNTs are acid cleavable, thereby providing a strong pH-responsive drug release, which may facilitate effective DOX release near the acidic tumor microenvironment and thus reduce its overall systemic toxicity. The DOX-loaded SWNTs were efficiently taken up by HepG2 tumor cells, and DOX was released intracellularly, as revealed by MTT assay and confocal microscope observations. Compared with SWNT-DOX conjugate formed by supramolecular interaction, the SWNT-HBA-DOX featured high weight loading and prolonged release of DOX, and thus improved its cytotoxicity against cancer cells. This study suggests that while SWNTs have great potential as a drug carrier, the efficient formulation strategy requires further study.Keywords: carbon nanotubes, drug delivery, controlled release, SWNTs
format	article
author	Gu YJ Cheng J Jin J Cheng SH Wong WT
author_facet	Gu YJ Cheng J Jin J Cheng SH Wong WT
author_sort	Gu YJ
title	Development and evaluation of pH-responsive single-walled carbon nanotube-doxorubicin complexes in cancer cells
title_short	Development and evaluation of pH-responsive single-walled carbon nanotube-doxorubicin complexes in cancer cells
title_full	Development and evaluation of pH-responsive single-walled carbon nanotube-doxorubicin complexes in cancer cells
title_fullStr	Development and evaluation of pH-responsive single-walled carbon nanotube-doxorubicin complexes in cancer cells
title_full_unstemmed	Development and evaluation of pH-responsive single-walled carbon nanotube-doxorubicin complexes in cancer cells
title_sort	development and evaluation of ph-responsive single-walled carbon nanotube-doxorubicin complexes in cancer cells
publisher	Dove Medical Press
publishDate	2011
url	https://doaj.org/article/5d07df47d667496194c04814673652c1
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Development and evaluation of pH-responsive single-walled carbon nanotube-doxorubicin complexes in cancer cells

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