MOE Key Laboratory of Macromolecular Synthesis and Functionalization, Department of Polymer Science and Engineering, Zhejiang University, Hangzhou 310027, China.
Biomaterials. 2013 Nov;34(33):8370-81. doi: 10.1016/j.biomaterials.2013.07.059. Epub 2013 Aug 7.
Multidentate ligands are expected to improve the performance of inorganic nanoparticles (NPs) in biological application. Designing robust multidentate ligands by a facile way and understanding the impact of ligand composition on NP's property are greatly important. We report the effective synthesis of hydrophilic copolymers containing pendent thiol groups along a polyethylene glycol (PEG) methacrylate backbone by classical free radical copolymerization. Gold nanoparticles (AuNPs) coated by these multidentate ligands with two different ratios of thiols to PEG segment (≈ 1:1 and 1:2) showed much higher colloidal stability in the presence of dithiothreitol (DTT) than AuNPs coated by monothiol-anchored PEG, and AuNPs coated by ligands with higher fraction of thiol groups showed slightly better resistance to DTT competition than did AuNPs coated by ligands with lower thiol fraction, but both of them exhibited excellent stabilities in biological media without obvious difference. In vitro study of uptake by macrophages did not showed significant difference between the two AuNPs with very low endocytosis. However, AuNPs coated by ligands with higher PEG content were found to accumulate in liver with a significantly lower level but a higher level in spleen than AuNPs coated by ligands with lower PEG contents. Moreover, the AuNPs coated with by ligands with higher PEG content showed higher tumor uptake. Additionally, AuNPs coated with both ligands demonstrated good biocompatibility as evaluated by cytotoxicity assays and histological analysis. Together, the composition of multidentate ligands will not only affect the stability of NPs under extreme conditions but also result in quite different fate of NPs in vivo, which can be tailored case by case.
多齿配体有望改善无机纳米粒子（NPs）在生物应用中的性能。通过简单的方法设计稳健的多齿配体，并了解配体组成对 NP 性能的影响非常重要。我们报告了通过经典自由基共聚，有效合成了含有沿聚乙二醇（PEG）甲基丙烯酸酯主链的悬垂巯基的亲水性共聚物。由两种不同比例的硫醇与 PEG 段（约 1:1 和 1:2）修饰的金纳米粒子（AuNPs）比由单巯基锚定的 PEG 修饰的 AuNPs 在存在二硫苏糖醇（DTT）时表现出更高的胶体稳定性，并且具有更高硫醇比例的配体修饰的 AuNPs 比具有较低硫醇比例的配体修饰的 AuNPs 对 DTT 竞争具有稍微更好的抗性，但它们在生物介质中均表现出极好的稳定性，没有明显差异。巨噬细胞摄取的体外研究表明，两种内吞作用非常低的 AuNPs 之间没有明显差异。然而，具有较高 PEG 含量的配体修饰的 AuNPs 被发现积聚在肝脏中的水平明显较低，但脾脏中的水平明显较高，而具有较低 PEG 含量的配体修饰的 AuNPs 则较低。此外，具有较高 PEG 含量的配体修饰的 AuNPs 表现出更高的肿瘤摄取。此外，由细胞毒性测定和组织学分析评估，两种配体修饰的 AuNPs 均表现出良好的生物相容性。总之，多齿配体的组成不仅会影响 NPs 在极端条件下的稳定性，而且还会导致 NPs 在体内的命运截然不同，这可以根据具体情况进行调整。
