| Registro completo |
| Provedor de dados: |
BJMBR
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| País: |
Brazil
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| Título: |
A conjugate of an anti-midkine single-chain variable fragment to doxorubicin inhibits tumor growth
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| Autores: |
Zhao,Shuli
Zhao,Guangfeng
Xie,Hao
Huang,Yahong
Hou,Yayi
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| Data: |
2012-03-01
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| Ano: |
2012
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| Palavras-chave: |
Single-chain variable fragments
Midkine
Tumor targeting
Doxorubicin
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| 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.
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| Tipo: |
Info:eu-repo/semantics/article
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| Idioma: |
Inglês
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| Identificador: |
http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0100-879X2012000300008
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| Editor: |
Associação Brasileira de Divulgação Científica
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| Relação: |
10.1590/S0100-879X2012007500009
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| Formato: |
text/html
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| Fonte: |
Brazilian Journal of Medical and Biological Research v.45 n.3 2012
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| Direitos: |
info:eu-repo/semantics/openAccess
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