Miller Lohra M, Young Tanner W, Wang Yi, Draper Benjamin E, Ye Xingchen, Jacobson Stephen C, Jarrold Martin F
Department of Chemistry, Indiana University, Bloomington, Indiana 47405, United States.
Anal Chem. 2024 Sep 3;96(35):14239-14247. doi: 10.1021/acs.analchem.4c02901. Epub 2024 Aug 21.
Nanotechnology has provided novel modalities for the delivery of therapeutic and diagnostic agents. In particular, nanoparticles (NPs) can be engineered at a low cost for drug loading and delivery. For example, silica NPs have proven useful as a controlled release platform for anti-inflammatory drugs. Despite the wide-ranging potential applications for NPs, robust characterization across all size ranges remains elusive. Electron microscopy (EM) is the conventional tool for measuring NP diameters. However, imitations in throughput and the inability to provide comprehensive information on physical properties, such as mass and density, without underlying assumptions, hinder a complete analysis. In addition, assessing sample heterogeneity, aggregation, or coalescence in solution by traditional EM analysis is not possible. Resistive-pulse sensing (RPS) provides a high throughput, solution-phase method for characterizing particle heterogeneity based on volume. Complementing these methods, charge detection mass spectrometry (CD-MS), a single particle technique, provides accurate mass information for heterogeneous samples including NPs. By combining EM, RPS and CD-MS, accurate volume, mass, and densities were obtained for silica NPs of various sizes. The results show that the density for 20 nm silica NPs is close to the density of fused silica (2.2 g/cm). Larger silica NPs were found to have densities that were either smaller or larger, while also falling outside the range of densities usually found for silica colloids and NPs (1.9-2.3 g/cm). Lower densities are attributed to pores (i.e., porous particles). For one sample, the mass distribution showed two components attributed to two populations of particles in the sample with different densities. The synergistic combination of EM, RPS, and CD-MS measurements outlined here for NP samples, allows much more extensive information to be obtained than from any of the techniques alone.
纳米技术为治疗和诊断药物的递送提供了新的方式。特别是，纳米颗粒（NPs）可以低成本进行设计用于药物负载和递送。例如，二氧化硅纳米颗粒已被证明是一种用于抗炎药物的控释平台。尽管纳米颗粒具有广泛的潜在应用，但对所有尺寸范围进行可靠的表征仍然难以实现。电子显微镜（EM）是测量纳米颗粒直径的传统工具。然而，通量方面的限制以及在没有潜在假设的情况下无法提供关于诸如质量和密度等物理性质的全面信息，阻碍了完整的分析。此外，通过传统的电子显微镜分析来评估溶液中的样品异质性、聚集或聚结是不可能的。电阻脉冲传感（RPS）提供了一种高通量的溶液相方法，用于基于体积表征颗粒异质性。作为这些方法的补充，电荷检测质谱（CD-MS）作为一种单颗粒技术，为包括纳米颗粒在内的异质样品提供准确的质量信息。通过结合电子显微镜、电阻脉冲传感和电荷检测质谱，获得了各种尺寸二氧化硅纳米颗粒的准确体积、质量和密度。结果表明，20纳米二氧化硅纳米颗粒的密度接近熔融二氧化硅的密度（2.2克/立方厘米）。发现较大的二氧化硅纳米颗粒的密度要么较小要么较大，同时也超出了通常在二氧化硅胶体和纳米颗粒中发现的密度范围（1.9 - 2.3克/立方厘米）。较低的密度归因于孔隙（即多孔颗粒）。对于一个样品，质量分布显示出两个组分，这归因于样品中具有不同密度的两种颗粒群体。这里概述的针对纳米颗粒样品的电子显微镜、电阻脉冲传感和电荷检测质谱测量的协同组合，能够获得比单独使用任何一种技术都更广泛的信息。
