In vivo performance of polymer nanocarriers dually-targeted to epitopes of the same or different receptors.
In vivo performance of polymer nanocarriers dually-targeted to epitopes of the same or different receptors.
复制标题
DOI：
10.1016/j.biomaterials.2013.01.069
复制
发表时间：
2013-04
期刊：
影响因子：
14
通讯作者：
Muro, Silvia
中科院分区：
文献类型：
--
作者：
Papademetriou, Iason T.;Garnacho, Carmen;Schuchman, Edward H.;Muro, Silvia
关键词：
利用促进靶向的亲和分子对药物传递纳米材料进行修饰，为细胞受体提供了一类新的配体，这些配体通常具有不同于天然配体的价态和尺寸。设计针对多个受体或同一受体上的多个表位的策略可能会调节这些纳米材料的生物分布特性。我们使用抗体定向靶向转铁蛋白受体(TFR)和细胞间黏附分子1(ICAM-1)的聚合物纳米载体来研究这一点。关于一个受体上的表位，与“游离”抗体相比，抗TFR-R17的纳米载体在小鼠中保持了脑靶向和肺靶向，而抗TFR-8D3纳米载体失去了特异性。用这两种抗体包裹纳米载体可以减少大脑和肝脏的靶向，而不是肺，从而调节生物分布。对于不同的受体，与单靶向纳米载体相比，包被抗ICAM和抗TFR的纳米载体在肺中的特异性蓄积中等，在肝脏中的特异性蓄积更高，而脑靶向与TFR-相当，但低于ICAM-1靶向的纳米载体。追踪一种模型治疗货物-酸性鞘磷脂酶(治疗Niemann-Pick病A-B的酶替代)显示，联合靶向的抗ICAM/TFR纳米载体与“游离”酶相比，增强了酶的传递，其生物分布模式与单靶向纳米载体不同。因此，将纳米载体定位于多个表位或受体有望控制药物输送纳米材料在体内的分布。
Modification of drug delivery nanomaterials with affinity molecules that facilitate targeting, has rendered a new class of ligands for cell receptors, which often possess valency and dimensions different from natural counterparts. Designing strategies to target multiple receptors or, never explored, multiple epitopes on the same receptor may modulate the biodistribution properties of these nanomaterials. We examined this using antibody-directed targeting of polymer nanocarriers to transferrin receptor (TfR) and intercellular adhesion molecule 1 (ICAM-1). Regarding epitopes on one receptor, nanocarriers addressed with anti-TfR-R17 maintained brain and lung targeting in mice, compared with “free” antibody, while anti-TfR-8D3 nanocarriers lost specificity. Coating nanocarriers with both antibodies decreased targeting in brain and liver, not lungs, modulating biodistribution. Regarding different receptors, nanocarriers coated with both anti-ICAM and anti-TfR displayed intermediate specific accumulation in lungs and higher in liver, compared to single-targeted nanocarriers, while brain targeting was comparable to TfR- and lower than ICAM-1-targeted nanocarriers. Tracing a model therapeutic cargo, acid sphingomyelinase (enzyme replacement for Niemann-Pick Disease A-B), showed that combined-targeted anti-ICAM/TfR nanocarriers enhanced enzyme delivery versus “free” enzyme, with biodistribution patterns different from single-targeted nanocarriers. Hence, targeting nanocarriers to multiple epitopes or receptors holds promise to control distribution of drug delivery nanomaterials in the body.
登录
查看更多内容
影响因子：
3.8
作者：
Boado, Ruben J.;Zhang, Yun;Wang, Yuntao;Pardridge, William M.
通讯作者：
Pardridge, William M.
DOI：
10.1083/jcb.201108131
发表时间：
2011-12-26
期刊：
The Journal of cell biology
影响因子：
--
作者：
Grove J;Marsh M
通讯作者：
Marsh M
影响因子：
10.8
作者：
Garnacho, Carmen;Albelda, Steven M.;Muro, Silvia
通讯作者：
Muro, Silvia
影响因子：
4.6
作者：
Chittasupho, Chuda;Xie, Sheng-Xue;Baoum, Abdulgader;Yakovleva, Tatyana;Siahaan, Teruna J.;Berkland, Cory J.
通讯作者：
Berkland, Cory J.
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