Biological evaluation of protein nanocapsules containing doxorubicin

Riki Toita,1,2 Masaharu Murata,1–3 Kana Abe,3 Sayoko Narahara,1 Jing Shu Piao,2 Jeong-Hun Kang,4 Kenoki Ohuchida,2,5 Makoto Hashizume1–31Innovation Center for Medical Redox Navigation, Kyushu University, 2Department of Advanced Medical Initiatives, Kyushu University, 3Center for...

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Autores principales:	Toita R, Murata M, Abe K, Narahara S, Piao JS, Kang JH, Ohuchida K, Hashizume M
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2013
Materias:	Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/86857e909919452db0ff65a51c9d74cf
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spelling	oai:doaj.org-article:86857e909919452db0ff65a51c9d74cf2021-12-02T02:42:07ZBiological evaluation of protein nanocapsules containing doxorubicin1176-91141178-2013https://doaj.org/article/86857e909919452db0ff65a51c9d74cf2013-05-01T00:00:00Zhttp://www.dovepress.com/biological-evaluation-of-protein-nanocapsules-containing-doxorubicin-a13085https://doaj.org/toc/1176-9114https://doaj.org/toc/1178-2013Riki Toita,1,2 Masaharu Murata,1–3 Kana Abe,3 Sayoko Narahara,1 Jing Shu Piao,2 Jeong-Hun Kang,4 Kenoki Ohuchida,2,5 Makoto Hashizume1–31Innovation Center for Medical Redox Navigation, Kyushu University, 2Department of Advanced Medical Initiatives, Kyushu University, 3Center for Advanced Medical Innovation, Kyushu University, Fukuoka, 4Department of Biomedical Engineering, National Cerebral and Cardiovascular Center Research Institutes, Suita, 5Department of Surgery and Oncology, Kyushu University, Fukuoka, JapanAbstract: This study describes the applications of a naturally occurring small heat shock protein (Hsp) that forms a cage-like structure to act as a drug carrier. Mutant Hsp cages (HspG41C) were expressed in Escherichia coli by substituting glycine 41 located inside the cage with a cysteine residue to allow conjugation with a fluorophore or a drug. The HspG41C cages were taken up by various cancer cell lines, mainly through clathrin-mediated endocytosis. The cages were detected in acidic organelles (endosomes/lysosomes) for at least 48 hours, but none were detected in the mitochondria or nuclei. To generate HspG41C cages carrying doxorubicin (DOX), an anticancer agent, the HspG41C cages and DOX were conjugated using acid-labile hydrazone linkers. The release of DOX from HspG41C cages was accelerated at pH 5.0, but was negligible at pH 7.2. The cytotoxic effects of HspG41C–DOX against Suit-2 and HepG2 cells were slightly weaker than those of free DOX, but the effects were almost identical in Huh-7 cells. Considering the relatively low release of DOX from HspG41C–DOX, HspG41C–DOX exhibited comparable activity towards HepG2 and Suit-2 cells and slightly stronger cytotoxicity towards Huh-7 cells than free DOX. Hsp cages offer good biocompatibility, are easy to prepare, and are easy to modify; these properties facilitate their use as nanoplatforms in drug delivery systems and in other biomedical applications.Keywords: anticancer activity, biomedical application, doxorubicin, drug delivery system, protein nanocapsules, small heat shock proteinToita RMurata MAbe KNarahara SPiao JSKang JHOhuchida KHashizume MDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2013, Iss default, Pp 1989-1999 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine (General) R5-920
spellingShingle	Medicine (General) R5-920 Toita R Murata M Abe K Narahara S Piao JS Kang JH Ohuchida K Hashizume M Biological evaluation of protein nanocapsules containing doxorubicin
description	Riki Toita,1,2 Masaharu Murata,1–3 Kana Abe,3 Sayoko Narahara,1 Jing Shu Piao,2 Jeong-Hun Kang,4 Kenoki Ohuchida,2,5 Makoto Hashizume1–31Innovation Center for Medical Redox Navigation, Kyushu University, 2Department of Advanced Medical Initiatives, Kyushu University, 3Center for Advanced Medical Innovation, Kyushu University, Fukuoka, 4Department of Biomedical Engineering, National Cerebral and Cardiovascular Center Research Institutes, Suita, 5Department of Surgery and Oncology, Kyushu University, Fukuoka, JapanAbstract: This study describes the applications of a naturally occurring small heat shock protein (Hsp) that forms a cage-like structure to act as a drug carrier. Mutant Hsp cages (HspG41C) were expressed in Escherichia coli by substituting glycine 41 located inside the cage with a cysteine residue to allow conjugation with a fluorophore or a drug. The HspG41C cages were taken up by various cancer cell lines, mainly through clathrin-mediated endocytosis. The cages were detected in acidic organelles (endosomes/lysosomes) for at least 48 hours, but none were detected in the mitochondria or nuclei. To generate HspG41C cages carrying doxorubicin (DOX), an anticancer agent, the HspG41C cages and DOX were conjugated using acid-labile hydrazone linkers. The release of DOX from HspG41C cages was accelerated at pH 5.0, but was negligible at pH 7.2. The cytotoxic effects of HspG41C–DOX against Suit-2 and HepG2 cells were slightly weaker than those of free DOX, but the effects were almost identical in Huh-7 cells. Considering the relatively low release of DOX from HspG41C–DOX, HspG41C–DOX exhibited comparable activity towards HepG2 and Suit-2 cells and slightly stronger cytotoxicity towards Huh-7 cells than free DOX. Hsp cages offer good biocompatibility, are easy to prepare, and are easy to modify; these properties facilitate their use as nanoplatforms in drug delivery systems and in other biomedical applications.Keywords: anticancer activity, biomedical application, doxorubicin, drug delivery system, protein nanocapsules, small heat shock protein
format	article
author	Toita R Murata M Abe K Narahara S Piao JS Kang JH Ohuchida K Hashizume M
author_facet	Toita R Murata M Abe K Narahara S Piao JS Kang JH Ohuchida K Hashizume M
author_sort	Toita R
title	Biological evaluation of protein nanocapsules containing doxorubicin
title_short	Biological evaluation of protein nanocapsules containing doxorubicin
title_full	Biological evaluation of protein nanocapsules containing doxorubicin
title_fullStr	Biological evaluation of protein nanocapsules containing doxorubicin
title_full_unstemmed	Biological evaluation of protein nanocapsules containing doxorubicin
title_sort	biological evaluation of protein nanocapsules containing doxorubicin
publisher	Dove Medical Press
publishDate	2013
url	https://doaj.org/article/86857e909919452db0ff65a51c9d74cf
work_keys_str_mv	AT toitar biologicalevaluationofproteinnanocapsulescontainingdoxorubicin AT muratam biologicalevaluationofproteinnanocapsulescontainingdoxorubicin AT abek biologicalevaluationofproteinnanocapsulescontainingdoxorubicin AT naraharas biologicalevaluationofproteinnanocapsulescontainingdoxorubicin AT piaojs biologicalevaluationofproteinnanocapsulescontainingdoxorubicin AT kangjh biologicalevaluationofproteinnanocapsulescontainingdoxorubicin AT ohuchidak biologicalevaluationofproteinnanocapsulescontainingdoxorubicin AT hashizumem biologicalevaluationofproteinnanocapsulescontainingdoxorubicin
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Biological evaluation of protein nanocapsules containing doxorubicin

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