How Carrier Size and Valency Modulate Receptor-Mediated Signaling: Understanding the Link between Binding and Endocytosis of ICAM-1-Targeted Carriers.
How Carrier Size and Valency Modulate Receptor-Mediated Signaling: Understanding the Link between Binding and Endocytosis of ICAM-1-Targeted Carriers.
复制标题
载体大小和价态如何调节受体介导的信号传导：了解 ICAM-1 靶向载体的结合和内吞作用之间的联系。
DOI：
10.1021/acs.biomac.6b00493
复制
发表时间：
2016
影响因子：
6.2
通讯作者：
Muro,Silvia
中科院分区：
文献类型：
--
作者：
Serrano,Daniel;Manthe,RachelL;Paul,Eden;Chadha,Rishi;Muro,Silvia
药物载体靶向内吞细胞受体促进细胞内药物递送。载体大小和靶向部分的数量（化合价）影响细胞结合和摄取。然而，这些参数如何影响受体介导的细胞信号传导（结合和摄取之间的联系）仍然没有得到表征。我们使用不同大小和化合价的聚合物载体研究了这一点，靶向内皮细胞间粘附分子-1（ICAM-1），这是一种在许多病理学中过度表达的标志物。出乎意料的是，细胞信号（神经酰胺和蛋白激酶C（PKC）富集和活化）和摄取的诱导与载体亲和力、每个细胞结合的载体总数、载体占据的累积细胞表面积、载体-细胞接触处的靶向抗体数量以及所有结合载体的累积受体结合无关。相反，“价密度”（每个载体表面积的抗体数量）支配信号传导，载体大小独立地影响摄取。这些结果是理解载体设计参数和受体介导的有利于内吞作用的信号传导之间相互作用的关键，对于细胞内药物递送至关重要。
Targeting of drug carriers to endocytic cell receptors facilitates intracellular drug delivery. Carrier size and number of targeting moieties (valency) influence cell binding and uptake. However, how these parameters influence receptor-mediated cell signaling (the link between binding and uptake) remains uncharacterized. We studied this using polymer carriers of different sizes and valencies, targeted to endothelial intercellular adhesion molecule-1 (ICAM-1), a marker overexpressed in many pathologies. Unexpectedly, induction of cell signals (ceramide and protein kinase C (PKC) enrichment and activation) and uptake, were independent of carrier avidity, total number of carriers bound per cell, cumulative cell surface area occupied by carriers, number of targeting antibodies at the carrier-cell contact, and cumulative receptor engagement by all bound carriers. Instead, “valency density” (number of antibodies per carrier surface area) ruled signaling, and carrier size independently influenced uptake. These results are key to understanding the interplay between carrier design parameters and receptor-mediated signaling conducive to endocytosis, paramount for intracellular drug delivery.
登录
查看更多内容
影响因子：
14
作者：
Zhang, Guodong;Yang, Zhi;Lu, Wei;Zhang, Rui;Huang, Qian;Tian, Mei;Li, Li;Liang, Dong;Li, Chun
通讯作者：
Li, Chun
DOI：
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：
--
作者：
Calderon AJ;Bhowmick T;Leferovich J;Burman B;Pichette B;Muzykantov V;Eckmann DM;Muro S
通讯作者：
Muro S
CD11/CD18 在猫肠系膜小静脉中剪切率依赖性白细胞-内皮细胞相互作用中的作用。
影响因子：
15.9
作者：
M. Perry;D N Granger
通讯作者：
D N Granger
DOI：
10.1016/j.jconrel.2014.06.008
发表时间：
2014-08-28
期刊：
Journal of controlled release : official journal of the Controlled Release Society
影响因子：
--
作者：
Papademetriou I;Tsinas Z;Hsu J;Muro S
通讯作者：
Muro S
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