Enhanced siRNA delivery into cells by exploiting the synergy between targeting ligands and cell-penetrating peptides.
Enhanced siRNA delivery into cells by exploiting the synergy between targeting ligands and cell-penetrating peptides.
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通过利用靶向配体和细胞穿透肽之间的协同作用，增强 siRNA 向细胞的递送。
DOI：
10.1016/j.biomaterials.2011.04.053
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发表时间：
2011-09
期刊：
影响因子：
14
通讯作者：
Saltzman, W. Mark
中科院分区：
文献类型：
--
作者：
Chene, Christopher J.;Saltzman, W. Mark
我们开发了一种基于聚合物纳米颗粒的siRNA递送系统，该系统利用靶向配体和细胞穿透肽之间的细胞表面结合协同作用。纳米颗粒通过聚乙二醇化磷脂连接体（DSPE-PEG）包裹叶酸和穿透素：这两种配体的结合代表了一种增强附着的聚合物纳米颗粒在细胞内传递的策略。表征纳米颗粒的大小，形态，表面修饰的密度，配体的结合和保留。dspe - peg包覆纳米颗粒的表面覆盖率与其他配体修饰的纳米级颗粒系统一样高（或更高）（~0.5-5 pmol配体/cm2）。此外，这些纳米颗粒还装载了高密度的siRNA（约130-140 pmol siRNA/mg纳米颗粒），这些siRNA在水中孵卵后会缓慢释放。这些装载sirna的纳米颗粒表面结合活性和细胞内化配体之间的协同作用，增强了它们在培养和肿瘤模型中的传递能力，提高了它们的基因沉默效果。传统上，靶向配体通过结合细胞表面受体发挥作用，而细胞穿透肽通过非特异性跨细胞膜运输发挥作用。有趣的是，我们已经观察到，这些双功能化纳米颗粒的改善递送部分是由于两种配体增加了细胞表面的亲和度。该siRNA传递系统提供了一种纳米载体表面修饰的方法，其中多个配体加性平行作用以增强细胞结合和摄取。
We have developed a polymer nanoparticle-based siRNA delivery system that exploits a cell-surface binding synergism between targeting ligands and cell-penetrating peptides. Nanoparticles were coated with folate and penetratin via a PEGylated phospholipid linker (DSPE-PEG): the combination of both of these ligands represents a strategy for enhancing intracellular delivery of attached polymer nanoparticles. Nanoparticles were characterized for size, morphology, density of surface modification, and ligand association and retention. The surface coverage achieved on DSPE-PEG-coated nanoparticles is as high as (or higher than) obtained with other ligand-modified nanoscale particulate systems (~0.5-5 pmol ligand/cm2). Additionally, these nanoparticles were loaded with a high density of siRNA (~130-140 pmol siRNA/mg nanoparticles), which is slowly released upon incubation in water. Synergies between the activity of surface binding and cell internalizing ligands on these siRNA-loaded nanoparticles impart delivery enhancements that improve their gene silencing efficacy both in culture and in tumor models. Traditionally, targeting ligands function by binding to cell surface receptors, while cell-penetrating peptides function by nonspecifically transporting across cell membranes. Interestingly, we have observed that improved delivery of these dual-functionalized nanoparticles was in part, a result of increased cell-surface avidity afforded by both ligands. This siRNA delivery system presents an approach to surface modification of nanovehicles, in which multiple ligands additively function in parallel to enhance cell binding and uptake.
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影响因子：
5.4
作者：
Cu, Yen;LeMoellic, Cathy;Caplan, Michael J.;Saltzman, W. Mark
通讯作者：
Saltzman, W. Mark
影响因子：
11.2
作者：
Pirollo, Kathleen F.;Rait, Antonina;Chang, Esther H.
通讯作者：
Chang, Esther H.
影响因子：
3.8
作者：
Ashok, B;Arleth, L;Önyüksel, H
通讯作者：
Önyüksel, H
影响因子：
14
作者：
Gref, R;Couvreur, P;Mysiakine, E
通讯作者：
Mysiakine, E
影响因子：
14
作者：
Andersen, Morten O.;Lichawska, Agata;Howard, Kenneth A.
通讯作者：
Howard, Kenneth A.