Modulation of endothelial targeting by size of antibody-antioxidant enzyme conjugates.
Modulation of endothelial targeting by size of antibody-antioxidant enzyme conjugates.
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根据抗体 - 抗氧化剂酶结合的大小对内皮靶向的调节。
DOI：
10.1016/j.jconrel.2010.10.026
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发表时间：
2011-02-10
期刊：
影响因子：
--
通讯作者：
Muzykantov VR
中科院分区：
文献类型：
--
作者：
Shuvaev VV;Tliba S;Pick J;Arguiri E;Christofidou-Solomidou M;Albelda SM;Muzykantov VR
抗氧化酶的内皮靶向作用减弱急性血管氧化应激的动物研究。超氧化物歧化酶（SOD）和过氧化氢酶与血小板-内皮细胞粘附分子-1抗体（抗PECAM/SOD和抗PECAM/过氧化氢酶）结合，与内皮细胞结合，在肺血管系统中蓄积，并对活性氧进行解毒。为了确定缀合物尺寸在内皮靶向的功效和特异性中的作用，我们合成了受控尺寸（40 nm-10，000 nm）的抗PECAM/酶缀合物。抗PECAM/酶与内皮细胞的结合随着缀合物尺寸从300 nm增加到2 μm（从结合分数的2.5%增加到8.5%）而增加，并且是特异性的，因为缀合物不与PECAM阴性细胞结合。对于200至800 nm的颗粒，小鼠静脉注射的抗PECAM/酶缀合物的肺摄取也从注射剂量的4.5%增加至16%。然而，大于300 nm的对照缀合物显示升高的非特异性肺摄取，表明抗PECAM/酶缀合物在体内的靶向特异性具有钟形曲线，其最大直径接近300 nm。这些结果表明：i）抗体/酶偶联物的大小调节靶向的功效和特异性，以及ii）应在体内定义最佳大小，以考虑难以在细胞培养中建模的参数。
Endothelial targeting of antioxidant enzymes attenuates acute vascular oxidative stress in animal studies. Superoxide dismutase (SOD) and catalase conjugated with antibodies to Platelet-Endothelial Cell Adhesion Molecule-1 (anti-PECAM/SOD and anti-PECAM/catalase) bind to endothelium, accumulate in the pulmonary vasculature, and detoxify reactive oxygen species. In order to define the role of conjugate size in the efficacy and specificity of endothelial targeting, we synthesized anti-PECAM/enzyme conjugates of controlled size (40 nm–10,000 nm). Binding of anti-PECAM/enzymes to endothelial cells increased with conjugate size from 300 nm to 2 μm (from 2.5 to 8.5% of bound fraction), and was specific, as conjugates did not bind to PECAM-negative cells. Pulmonary uptake of anti-PECAM/enzyme conjugates injected intravenously in mice also increased from 4.5 to 16% of Injected Dose for particles from 200 to 800 nm. However, control conjugates larger than 300 nm showed elevated non-specific pulmonary uptake, indicating that the targeting specificity of anti-PECAM/enzyme conjugates in vivo has a bell-shaped curve with a maximum close to 300-nm diameter. These results show that: i) the size of an antibody/enzyme conjugate modulates efficacy and specificity of targeting, and ii) a size optimum should be defined in vivo to account for parameters that are difficult to model in cell culture.
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DOI：
10.1002/wnan.40
发表时间：
2009-07
影响因子：
8.6
作者：
Canelas, Dorian A.;Herlihy, Kevin P.;DeSimone, Joseph M.
通讯作者：
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影响因子：
6.6
作者：
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DOI：
10.1073/pnas.93.11.5213
发表时间：
1996-05-28
影响因子：
11.1
作者：
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通讯作者：
Fisher, AB
影响因子：
6.6
作者：
Simone EA;Dziubla TD;Muzykantov VR
通讯作者：
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影响因子：
38.3
作者：
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