Brain tumor tandem targeting using a combination of monoclonal antibodies attached to biopoly(β-L-malic acid)
Brain tumor tandem targeting using a combination of monoclonal antibodies attached to biopoly(β-L-malic acid)
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DOI：
10.1016/j.jconrel.2007.05.032
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发表时间：
2007-10-08
影响因子：
10.8
通讯作者：
Ljubimova, Julia Y.
中科院分区：
文献类型：
--
作者：
Fujita, Manabu;Lee, Bong-Seop;Ljubimova, Julia Y.
利用纳米技术实现肿瘤特异性靶向治疗是提高抗肿瘤药物疗效的主要途径。为了改善药物靶向，我们首次将两种不同的单克隆抗体，抗小鼠转铁蛋白受体抗体和小鼠自身免疫性抗核小体抗体2C 5共价缀合到药物递送纳米平台聚（β-L-苹果酸）上。活性抗肿瘤药物成分连接到同一个载体分子是血管蛋白层粘连蛋白-8的反义寡核苷酸。由此产生的药物，一种新的Polycefin变体，通过静脉注射给药到带有神经胶质瘤的异种动物。药物递送系统通过抗小鼠转移受体抗体靶向穿过小鼠内皮系统，并通过抗核小体抗体2C 5靶向至肿瘤细胞表面。在体外和体内比较携带两种抗体或每种单一抗体的头孢菌素变体的靶向效力。ELISA证实了两种抗体在同一纳米平台分子上的共存及其功能活性。静脉注射24小时后的荧光成像分析表明，与单一抗体相比，具有串联抗体构型的Polycefin变体的肿瘤蓄积显著更高。结果表明，与药物递送载体携带的单一构型相比，串联构型的抗体的功效得到改善。(C)2007 Elsevier B. V.保留所有权利。
Tumor-specific targeting using achievements of nanotechnology is a mainstay of increasing efficacy of anti-tumor drugs. To improve drug targeting we covalently conjugated for the first time two different monoclonal antibodies, an anti-mouse transferrin receptor antibody and a mouse autoimmune anti-nucleosome antibody 2C5, onto the drug delivery nanoplatform, poly(beta-L-malic acid). The active anti-tumor drug components attached to the same carrier molecule were antisense oligonucleotides to vascular protein laminin-8. The resulting drug, a new Polycefin variant, was administered intravenously into glioma-bearing xenogeneic animals. The drug delivery system was targeted across mouse endothelial system by the anti-mouse transferring receptor antibody and to the tumor cell surface by the anti-nucleosome antibody 2C5. The targeting efficacies of the Polycefin variants bearing either two antibodies or each single antibody were compared in vitro and in vivo. ELISA confirmed the co-existence of two antibodies on the same nanoplatform molecule and their functional activities. Fluorescence imaging analysis after 24 h of intravenous injection demonstrated significantly higher tumor accumulation of Polycefin variants with the tandem configuration of antibodies than with single antibodies. The results suggest improved efficacy for tandem configuration of antibodies than for single configurations carried by a drug delivery vehicle. (C) 2007 Elsevier B.V. All rights reserved.