کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
6486326 424 2015 8 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Minimizing antibody surface density on liposomes while sustaining cytokine-activated EC targeting
موضوعات مرتبط
مهندسی و علوم پایه مهندسی شیمی بیو مهندسی (مهندسی زیستی)
پیش نمایش صفحه اول مقاله
Minimizing antibody surface density on liposomes while sustaining cytokine-activated EC targeting
چکیده انگلیسی
Liposomes may be engineered to target inflamed endothelium by mimicking ligand-receptor interactions between leukocytes and cytokine-activated endothelial cells (ECs). The upregulation and assembly of vascular cell adhesion molecule-1 (VCAM1) and E-selectin on the cell membrane upon exposure to cytokines have shown potential for drug delivery vehicles to target sites of chronic endothelial inflammation, such as atherosclerosis and cancer. Herein, we characterized EC surfaces by measuring the E-selectin and VCAM1 surface densities and adhesion forces of aVCAM1 and aE-selectin to ECs. We quantified the antibody density, ratio, and diffusivity of liposomes to achieve significant binding and internalization. At 1 h, the 1:1 ratio of VCAM1:E-selectin antibodies was significantly higher than 1:0 and 0:1. Significant binding and uptake was achieved at aE-selectin densities as low as 400 molecules/μm2. The highest levels of binding and uptake were achieved when using a 1:1 ratio of VCAM1:E-selectin antibodies at a density of 1000 molecules/μm2; this density is 85% lower than previous reports. The binding and uptake of functionalized liposomes were reduced to levels comparable to IgG functionalized liposomes upon a 10-fold reduction in liposome membrane diffusivity. We conclude with a liposomal design that discriminates between healthy and inflamed endothelium while reducing antibody surface presentation.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biomaterials - Volume 41, February 2015, Pages 37-44
نویسندگان
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