کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1425582 986771 2011 6 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Modulation of endothelial targeting by size of antibody–antioxidant enzyme conjugates
موضوعات مرتبط
مهندسی و علوم پایه مهندسی مواد بیومتریال
پیش نمایش صفحه اول مقاله
Modulation of endothelial targeting by size of antibody–antioxidant enzyme conjugates
چکیده انگلیسی

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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ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Controlled Release - Volume 149, Issue 3, 10 February 2011, Pages 236–241
نویسندگان
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