Effect of flow on endothelial endocytosis of nanocarriers targeted to ICAM-1.
Effect of flow on endothelial endocytosis of nanocarriers targeted to ICAM-1.
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DOI：
10.1016/j.jconrel.2011.09.067
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发表时间：
2012-02-10
期刊：
影响因子：
--
通讯作者：
Muro S
中科院分区：
文献类型：
--
作者：
Bhowmick T;Berk E;Cui X;Muzykantov VR;Muro S
通过靶向内皮细胞决定因子的纳米载体将药物输送到内皮细胞可能改善血管疾病的治疗。这就是细胞间粘附分子1 （ICAM-1）的情况，这是一种在许多病理中内皮细胞（ECs）上过度表达的糖蛋白。靶向icam -1的纳米载体通过cam介导的内吞作用这一非经典途径与ECs结合并被ECs内化。在这项工作中，我们研究了内皮细胞对生理流动的适应对靶向ICAM-1（抗icam /NCs，直径~180 nm）的模型聚合物纳米载体内吞的影响。建立内皮样细胞（EAhy926细胞）和原代人脐静脉内皮细胞（HUVECs）在4 dyn/cm2的层流剪切应力下培养24小时，细胞伸长并形成与流动方向一致的肌动蛋白应力纤维。荧光显微镜显示，与静态孵育下的非流动适应细胞相比，流动适应细胞在流动条件下内化抗icam /NCs的速度较慢（约减少35%）。阿米洛利抑制了icam /NC的摄取，而菲利平和尸胺则对其影响不大，这表明cam -内吞作用是流动状态下抗icam /NC摄取的原因。抑制蛋白激酶C对流动内化的影响更为温和，蛋白激酶C在cam -内吞过程中调节肌动蛋白重塑。在这种情况下，维持细胞形状的应力纤维中的肌动蛋白募集可能会通过干扰cam -内吞作用所需的肌动蛋白重组而延迟抗icam / nc的摄取。电镜显示，小鼠静脉注射后，肺内皮对抗icam /NCs的内吞作用有些缓慢，但有效，与流式适应细胞培养相似：约40%（30分钟）和80%（3小时）内吞。与细胞培养数据相似，在剪切应力较低的毛细血管中，吸收速度略快。此外，LPS处理加速了小鼠抗icam /NCs的内化。因此，通过血流和内皮状态调节icam -1靶向纳米载体的内吞作用可能会调节药物递送到暴露于不同生理（毛细血管vs.小动脉/小静脉）或病理（缺血、炎症）水平和血流模式的内皮细胞中。
Delivery of drugs into the endothelium by nanocarriers targeted to endothelial determinants may improve treatment of vascular maladies. This is the case for intercellular adhesion molecule 1 (ICAM-1), a glycoprotein overexpressed on endothelial cells (ECs) in many pathologies. ICAM-1-targeted nanocarriers bind to and are internalized by ECs via a non-classical pathway, CAM-mediated endocytosis. In this work we studied the effects of endothelial adaptation to physiological flow on the endocytosis of model polymer nanocarriers targeted to ICAM-1 (anti-ICAM/NCs, ~180-nm diameter). Culturing established endothelial-like cells (EAhy926 cells) and primary human umbilical vein ECs (HUVECs) under 4 dyn/cm2 laminar shear stress for 24 h resulted in flow adaptation: cell elongation and formation of actin stress fibers aligned to the flow direction. Fluorescence microscopy showed that flow-adapted cells internalized anti-ICAM/NCs under flow, although at slower rate versus non flow-adapted cells under static incubation (~35% reduction). Uptake was inhibited by amiloride, whereas marginally affected by filipin and cadaverine, implicating that CAM-endocytosis accounts for anti-ICAM/NC uptake under flow. Internalization under flow was more modestly affected by inhibiting protein kinase C, which regulates actin remodeling during CAM-endocytosis. Actin recruitment to stress fibers that maintain the cell shape under flow may delay uptake of anti-ICAM/NCs under this condition by interfering with actin reorganization needed for CAM-endocytosis. Electron microscopy revealed somewhat slow, yet effective endocytosis of anti-ICAM/NCs by pulmonary endothelium after i.v. injection in mice, similar to that of flow-adapted cell cultures: ~40% (30 min) and 80% (3 h) internalization. Similar to cell culture data, uptake was slightly faster in capillaries with lower shear stress. Further, LPS treatment accelerated internalization of anti-ICAM/NCs in mice. Therefore, regulation of endocytosis of ICAM-1-targeted nanocarriers by flow and endothelial status may modulate drug delivery into ECs exposed to different physiological (capillaries vs. arterioles/venules) or pathological (ischemia, inflammation) levels and patterns of blood flow.
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VCAM-1和ICAM-1与粘附白细胞的新型内皮对接结构中的动态相互作用。
DOI：
10.1083/jcb.200112126
发表时间：
2002-06-24
期刊：
The Journal of cell biology
影响因子：
--
作者：
Barreiro O;Yanez-Mo M;Serrador JM;Montoya MC;Vicente-Manzanares M;Tejedor R;Furthmayr H;Sanchez-Madrid F
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10.1016/j.jconrel.2010.10.025
发表时间：
2011-02-28
期刊：
Journal of controlled release : official journal of the Controlled Release Society
影响因子：
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作者：
Calderon AJ;Bhowmick T;Leferovich J;Burman B;Pichette B;Muzykantov V;Eckmann DM;Muro S
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Muro S
DOI：
10.1073/pnas.1006611107
发表时间：
2010-09-21
影响因子：
11.1
作者：
Liu, Jin;Weller, Gregory E. R.;Radhakrishnan, Ravi
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DOI：
10.1016/j.jconrel.2010.10.031
发表时间：
2011-02-10
期刊：
Journal of controlled release : official journal of the Controlled Release Society
影响因子：
--
作者：
Hsu J;Serrano D;Bhowmick T;Kumar K;Shen Y;Kuo YC;Garnacho C;Muro S
通讯作者：
Muro S
影响因子：
3.4
作者：
Mastrobattista, E;Storm, G;Henricks, PAJ
通讯作者：
Henricks, PAJ