A conjugate of an anti-midkine single-chain variable fragment to doxorubicin inhibits tumor growth.
A conjugate of an anti-midkine single-chain variable fragment to doxorubicin inhibits tumor growth.
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DOI：
10.1590/s0100-879x2012007500009
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发表时间：
2012-03
期刊：
影响因子：
--
通讯作者：
Hou Y
中科院分区：
文献类型：
--
作者：
Zhao S;Zhao G;Xie H;Huang Y;Hou Y
将阿霉素(DOX)偶联到抗人中期因子(MK)的单链可变区(ScFv)上，并将该偶联物(scFv-DOX)用于靶向高表达人MK的小鼠实体瘤模型。His标记的重组单链抗体在细菌中表达，金属亲和层析纯化，然后以氧化葡聚糖(Dex)为连接物连接到DOX上。该免疫结合物的分子式为scFv(Dex)1.3(DOX)20。体外细胞凋亡实验表明，scFv-DOX结合物对MK转染人BGC823-MK细胞的细胞毒作用明显高于未转染人BGC823-MK细胞(55.3±2.4vs22.4±3.8%)。荷BGC823-MK实体瘤裸鼠分别给予ScFv-DOX或等剂量的ScFv+DOX治疗2周，ScFv-DOX结合物对肿瘤生长的抑制作用明显优于ScFv+DOX(51.83%vs40.81%)。肿瘤组织的组织学分析显示，单链抗体-多柔比星治疗的小鼠肿瘤中积累了最高水平的多柔比星，这导致了比同等剂量的单链抗体+多柔比星治疗组更广泛的肿瘤细胞死亡。这些结果表明，scFv-DOX结合物在体内有效地抑制了肿瘤的生长，提示抗原特异性的scFv可能是合格的药物载体。
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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DOI：
10.1093/protein/11.1.65
发表时间：
1998-01-01
期刊：
PROTEIN ENGINEERING
影响因子：
--
作者：
Dougan, DA;Malby, RL;Hudson, PJ
通讯作者：
Hudson, PJ
DOI：
10.1016/j.bbrc.2007.04.183
发表时间：
2007-07-06
影响因子：
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作者：
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作者：
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影响因子：
2.4
作者：
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影响因子：
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作者：
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