Data/hora: 15/06/2024 12:18:07

Provedor de dados: | 56
País: | Brazil
Título: | A conjugate of an anti-midkine single-chain variable fragment to doxorubicin inhibits tumor growth
Autores: | Zhao,Shuli; Zhao,Guangfeng; Xie,Hao; Huang,Yahong; Hou,Yayi.
Data: | 2012-03-01
Ano: | 2012
Palavras-chave: | Single-chain variable fragments; Midkine; Tumor targeting; Doxorubicin.
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.
Tipo: | Info:eu-repo/semantics/article
Idioma: | Inglês
Identificador: | http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0100-879X2012000300008
Editor: | Associação Brasileira de Divulgação Científica
Relação: | 10.1590/S0100-879X2012007500009
Formato: | text/html
Fonte: | Brazilian Journal of Medical and Biological Research  v.45 n.3 2012
Fonte: | info:eu-repo/semantics/openAccess