Chemistry Department, University of Michigan, Ann Arbor, Michigan 48109-1055, USA.
Acc Chem Res. 2011 Nov 15;44(11):1135-45. doi: 10.1021/ar1001389. Epub 2011 Aug 3.
Nanoparticles conjugated with functional ligands are expected to have a major impact in medicine, photonics, sensing, and nanoarchitecture design. One major obstacle to realizing the promise of these materials, however, is the difficulty in controlling the ligand/nanoparticle ratio. This obstacle can be segmented into three key areas: First, many designs of these systems have failed to account for the true heterogeneity of ligand/nanoparticle ratios that compose each material. Second, studies in the field often use the mean ligand/nanoparticle ratio as the accepted level of characterization of these materials. This measure is insufficient because it does not provide information about the distribution of ligand/nanoparticle species within a sample or the number and relative amount of the different species that compose a material. Without these data, researchers do not have an accurate definition of material composition necessary both to understand the material-property relationships and to monitor the consistency of the material. Third, some synthetic approaches now in use may not produce consistent materials because of their sensitivity to reaction kinetics and to the synthetic history of the nanoparticle. In this Account, we describe recent advances that we have made in under standing the material composition of ligand-nanoparticle systems. Our work has been enabled by a model system using poly(amidoamine) dendrimers and two small molecule ligands. Using reverse phase high-pressure liquid chromatography (HPLC), we have successfully resolved and quantified the relative amounts and ratios of each ligand/dendrimer combination. This type of information is rare within the field of ligand-nanoparticle materials because most analytical techniques have been unable to identify the components in the distribution. Our experimental data indicate that the actual distribution of ligand-nanoparticle components is much more heterogeneous than is commonly assumed. The mean ligand/nanoparticle ratio that is typically the only information known about a material is insufficient because the mean does not provide information on the diversity of components in the material and often does not describe the most common component (the mode). Additionally, our experimental data has provided examples of material batches with the same mean ligand/nanoparticle ratio and very different distributions. This discrepancy indicates that the mean cannot be used as the sole metric to assess the reproducibility of a system. We further found that distribution profiles can be highly sensitive to the synthetic history of the starting material as well as slight changes in reaction conditions. We have incorporated the lessons from our experimental data into the design of new ligand-nanoparticle systems to provide improved control over these ratios.
与功能配体结合的纳米粒子有望在医学、光子学、传感和纳米结构设计领域产生重大影响。然而，实现这些材料的承诺的一个主要障碍是难以控制配体/纳米粒子的比例。这个障碍可以分为三个关键领域：首先，许多这类系统的设计未能考虑到构成每种材料的配体/纳米粒子比的真正异质性。其次，该领域的研究通常使用平均配体/纳米粒子比作为对这些材料的公认特征水平。这种测量方法是不够的，因为它没有提供关于样品内配体/纳米粒子种类分布的信息，也没有提供组成材料的不同种类的数量和相对量的信息。没有这些数据，研究人员就无法准确地定义材料组成，这对于理解材料性能关系和监测材料的一致性都是必要的。第三，由于对反应动力学和纳米粒子的合成历史敏感，一些目前使用的合成方法可能无法产生一致的材料。在本报告中，我们描述了我们在理解配体-纳米粒子系统的材料组成方面所取得的最新进展。我们的工作得益于使用聚（酰胺-胺）树枝状大分子和两种小分子配体的模型系统。我们使用反相高压液相色谱（HPLC）成功地分离和定量了每种配体/树枝状大分子组合的相对量和比例。在配体-纳米粒子材料领域，这种类型的信息非常罕见，因为大多数分析技术都无法识别分布中的成分。我们的实验数据表明，配体-纳米粒子成分的实际分布比通常假设的要复杂得多。通常情况下，人们只知道一种材料的平均配体/纳米粒子比，这是不够的，因为平均值没有提供材料中成分多样性的信息，而且通常也没有描述最常见的成分（模式）。此外，我们的实验数据提供了具有相同平均配体/纳米粒子比但分布非常不同的材料批次的示例。这种差异表明，平均值不能用作评估系统可重复性的唯一指标。我们进一步发现，分布轮廓对起始材料的合成历史以及反应条件的微小变化非常敏感。我们已经将实验数据中的经验教训纳入到新的配体-纳米粒子系统的设计中，以提供对这些比例的更好控制。
