A conjugate of an anti-midkine single-chain variable fragment to doxorubicin inhibits tumor growth

Detalhes bibliográficos
Autor(a) principal: Zhao,Shuli
Data de Publicação: 2012
Outros Autores: Zhao,Guangfeng, Xie,Hao, Huang,Yahong, Hou,Yayi
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Brazilian Journal of Medical and Biological Research
Texto Completo: http://old.scielo.br/scielo.php?script=sci_arttext&pid=S0100-879X2012000300008
Resumo: Doxorubicin (DOX) was conjugated to a single-chain variable fragment (scFv) against human midkine (MK), and the conjugate (scFv-DOX) was used to target the chemotherapeutic agent to a mouse solid tumor model in which the tumor cells expressed high levels of human MK. The His-tagged recombinant scFv was expressed in bacteria, purified by metal affinity chromatography, and then conjugated to DOX using oxidative dextran (Dex) as a linker. The molecular formula of this immunoconjugate was scFv(Dex)1.3(DOX)20. In vitro apoptosis assays showed that the scFv-DOX conjugate was more cytotoxic against MK-transfected human adenocarcinoma cells (BGC823-MK) than untransfected cells (55.3 ± 2.4 vs 22.4 ± 3.8%) for three independent experiments. Nude mice bearing BGC823-MK solid tumors received scFv-DOX or equivalent doses of scFv + DOX for 2 weeks and tumor growth was more effectively inhibited by the scFv-DOX conjugate than by scFv + DOX (51.83% inhibition vs 40.81%). Histological analysis of the tumor tissues revealed that the highest levels of DOX accumulated in tumors from mice treated with scFv-DOX and this resulted in more extensive tumor cell death than in animals treated with the equivalent dose of scFv + DOX. These results show that the scFv-DOX conjugate effectively inhibited tumor growth in vivo and suggest that antigen-specific scFv may be competent drug-carriers.
id ABDC-1_e89b013c52115202f4c18d0d0f1d2337
oai_identifier_str oai:scielo:S0100-879X2012000300008
network_acronym_str ABDC-1
network_name_str Brazilian Journal of Medical and Biological Research
repository_id_str
spelling A conjugate of an anti-midkine single-chain variable fragment to doxorubicin inhibits tumor growthSingle-chain variable fragmentsMidkineTumor targetingDoxorubicinDoxorubicin (DOX) was conjugated to a single-chain variable fragment (scFv) against human midkine (MK), and the conjugate (scFv-DOX) was used to target the chemotherapeutic agent to a mouse solid tumor model in which the tumor cells expressed high levels of human MK. The His-tagged recombinant scFv was expressed in bacteria, purified by metal affinity chromatography, and then conjugated to DOX using oxidative dextran (Dex) as a linker. The molecular formula of this immunoconjugate was scFv(Dex)1.3(DOX)20. In vitro apoptosis assays showed that the scFv-DOX conjugate was more cytotoxic against MK-transfected human adenocarcinoma cells (BGC823-MK) than untransfected cells (55.3 ± 2.4 vs 22.4 ± 3.8%) for three independent experiments. Nude mice bearing BGC823-MK solid tumors received scFv-DOX or equivalent doses of scFv + DOX for 2 weeks and tumor growth was more effectively inhibited by the scFv-DOX conjugate than by scFv + DOX (51.83% inhibition vs 40.81%). Histological analysis of the tumor tissues revealed that the highest levels of DOX accumulated in tumors from mice treated with scFv-DOX and this resulted in more extensive tumor cell death than in animals treated with the equivalent dose of scFv + DOX. These results show that the scFv-DOX conjugate effectively inhibited tumor growth in vivo and suggest that antigen-specific scFv may be competent drug-carriers.Associação Brasileira de Divulgação Científica2012-03-01info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersiontext/htmlhttp://old.scielo.br/scielo.php?script=sci_arttext&pid=S0100-879X2012000300008Brazilian Journal of Medical and Biological Research v.45 n.3 2012reponame:Brazilian Journal of Medical and Biological Researchinstname:Associação Brasileira de Divulgação Científica (ABDC)instacron:ABDC10.1590/S0100-879X2012007500009info:eu-repo/semantics/openAccessZhao,ShuliZhao,GuangfengXie,HaoHuang,YahongHou,Yayieng2012-03-12T00:00:00Zoai:scielo:S0100-879X2012000300008Revistahttps://www.bjournal.org/https://old.scielo.br/oai/scielo-oai.phpbjournal@terra.com.br||bjournal@terra.com.br1414-431X0100-879Xopendoar:2012-03-12T00:00Brazilian Journal of Medical and Biological Research - Associação Brasileira de Divulgação Científica (ABDC)false
dc.title.none.fl_str_mv A conjugate of an anti-midkine single-chain variable fragment to doxorubicin inhibits tumor growth
title A conjugate of an anti-midkine single-chain variable fragment to doxorubicin inhibits tumor growth
spellingShingle A conjugate of an anti-midkine single-chain variable fragment to doxorubicin inhibits tumor growth
Zhao,Shuli
Single-chain variable fragments
Midkine
Tumor targeting
Doxorubicin
title_short A conjugate of an anti-midkine single-chain variable fragment to doxorubicin inhibits tumor growth
title_full A conjugate of an anti-midkine single-chain variable fragment to doxorubicin inhibits tumor growth
title_fullStr A conjugate of an anti-midkine single-chain variable fragment to doxorubicin inhibits tumor growth
title_full_unstemmed A conjugate of an anti-midkine single-chain variable fragment to doxorubicin inhibits tumor growth
title_sort A conjugate of an anti-midkine single-chain variable fragment to doxorubicin inhibits tumor growth
author Zhao,Shuli
author_facet Zhao,Shuli
Zhao,Guangfeng
Xie,Hao
Huang,Yahong
Hou,Yayi
author_role author
author2 Zhao,Guangfeng
Xie,Hao
Huang,Yahong
Hou,Yayi
author2_role author
author
author
author
dc.contributor.author.fl_str_mv Zhao,Shuli
Zhao,Guangfeng
Xie,Hao
Huang,Yahong
Hou,Yayi
dc.subject.por.fl_str_mv Single-chain variable fragments
Midkine
Tumor targeting
Doxorubicin
topic Single-chain variable fragments
Midkine
Tumor targeting
Doxorubicin
description Doxorubicin (DOX) was conjugated to a single-chain variable fragment (scFv) against human midkine (MK), and the conjugate (scFv-DOX) was used to target the chemotherapeutic agent to a mouse solid tumor model in which the tumor cells expressed high levels of human MK. The His-tagged recombinant scFv was expressed in bacteria, purified by metal affinity chromatography, and then conjugated to DOX using oxidative dextran (Dex) as a linker. The molecular formula of this immunoconjugate was scFv(Dex)1.3(DOX)20. In vitro apoptosis assays showed that the scFv-DOX conjugate was more cytotoxic against MK-transfected human adenocarcinoma cells (BGC823-MK) than untransfected cells (55.3 ± 2.4 vs 22.4 ± 3.8%) for three independent experiments. Nude mice bearing BGC823-MK solid tumors received scFv-DOX or equivalent doses of scFv + DOX for 2 weeks and tumor growth was more effectively inhibited by the scFv-DOX conjugate than by scFv + DOX (51.83% inhibition vs 40.81%). Histological analysis of the tumor tissues revealed that the highest levels of DOX accumulated in tumors from mice treated with scFv-DOX and this resulted in more extensive tumor cell death than in animals treated with the equivalent dose of scFv + DOX. These results show that the scFv-DOX conjugate effectively inhibited tumor growth in vivo and suggest that antigen-specific scFv may be competent drug-carriers.
publishDate 2012
dc.date.none.fl_str_mv 2012-03-01
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://old.scielo.br/scielo.php?script=sci_arttext&pid=S0100-879X2012000300008
url http://old.scielo.br/scielo.php?script=sci_arttext&pid=S0100-879X2012000300008
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv 10.1590/S0100-879X2012007500009
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv text/html
dc.publisher.none.fl_str_mv Associação Brasileira de Divulgação Científica
publisher.none.fl_str_mv Associação Brasileira de Divulgação Científica
dc.source.none.fl_str_mv Brazilian Journal of Medical and Biological Research v.45 n.3 2012
reponame:Brazilian Journal of Medical and Biological Research
instname:Associação Brasileira de Divulgação Científica (ABDC)
instacron:ABDC
instname_str Associação Brasileira de Divulgação Científica (ABDC)
instacron_str ABDC
institution ABDC
reponame_str Brazilian Journal of Medical and Biological Research
collection Brazilian Journal of Medical and Biological Research
repository.name.fl_str_mv Brazilian Journal of Medical and Biological Research - Associação Brasileira de Divulgação Científica (ABDC)
repository.mail.fl_str_mv bjournal@terra.com.br||bjournal@terra.com.br
_version_ 1754302941195403264