Controlling ligand surface density optimizes nanoparticle binding to ICAM-1.
Controlling ligand surface density optimizes nanoparticle binding to ICAM-1.
复制标题
DOI：
10.1002/jps.22342
复制
发表时间：
2011-03
影响因子：
3.8
通讯作者：
Berkland, Cory
中科院分区：
文献类型：
--
作者：
Fakhari, Amir;Baoum, Abdulgader;Siahaan, Teruna J.;Le, Khoi Ba;Berkland, Cory
关键词：
在感染过程中，病原体利用表面受体进入细胞内区室。导致病原体内化的多种受体-配体相互作用已经被鉴定，并且多价配体结合作为促进内化的手段的重要性已经出现。然而，配体密度的影响却鲜为人知。在本研究中，使用聚（dl-乳酸-共-乙醇酸）纳米颗粒（PLGA NPs）检查配体密度。使用环肽cLABL作为靶向部分，因为它是细胞间细胞粘附分子-1（ICAM-1）的已知配体。为了调节PLGA NP表面上的反应性位点的数量，将具有羧基的改性Pluronic®和具有羟基的Pluronic®以不同比例组合，并检查颗粒性质。利用表面活性剂混合物直接影响颗粒电荷和cLABL缀合的反应位点的数量。cLABL肽的表面密度随着反应性Pluronic®的相对量增加而增加。使用致癌的人肺泡基底上皮细胞（A549）的研究表明，cLABL密度可以被优化以改善细胞摄取。这些结果补充了其他研究，表明应考虑NP表面上靶向部分的表面密度以增强用于细胞靶向的配体的效果。
During infection, pathogens utilize surface receptors to gain entry into intracellular compartments. Multiple receptor-ligand interactions that lead to pathogen internalization have been identified and the importance of multivalent ligand binding as a means to facilitate internalization has emerged. The effect of ligand density, however; is less well known. In this study, ligand density was examined using poly(dl-lactic-co-glycolic acid) nanoparticles (PLGA NPs). A cyclic peptide, cLABL, was used as a targeting moiety as it is a known ligand for intercellular cell adhesion molecule-1 (ICAM-1). To modulate the number of reactive sites on the surface of PLGA NPs, modified Pluronic® with carboxyl groups and Pluronic® with hydroxyl groups were combined at different ratios and the particle properties were examined. Utilizing a surfactant mixture directly affected the particle charge and the number of reactive sites for cLABL conjugation. The surface density of cLABL peptide increased as the relative amount of reactive Pluronic® was increased. Studies using carcinomic human alveolar basal epithelial cells (A549) showed that cLABL density may be optimized to improve cellular uptake. These results compliment other studies suggesting surface density of the targeting moiety on the NP surface should be considered to enhance the effect of ligands employed for cell targeting.
登录
查看更多内容
影响因子：
4.7
作者：
Gabizon, A;Horowitz, AT;Zalipsky, S
通讯作者：
Zalipsky, S
影响因子：
14
作者：
Gref, R;Couvreur, P;Mysiakine, E
通讯作者：
Mysiakine, E
影响因子：
2.2
作者：
Choi, SW;Kim, WS;Kim, JH
通讯作者：
Kim, JH
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.
影响因子：
10.8
作者：
Mo, Y;Lim, LY
通讯作者：
Lim, LY