Vaskan I S, Prikhodko A T, Petoukhov M V, Shtykova E V, Bovin N V, Tuzikov A B, Oleinikov V A, Zalygin A V
Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow 117997, Russia.
Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow 117997, Russia; National Research Nuclear University Moscow Engineering Physics Institute, Moscow 115409, Russia.
Colloids Surf B Biointerfaces. 2023 Apr;224:113183. doi: 10.1016/j.colsurfb.2023.113183. Epub 2023 Feb 2.
For the biomedical applications of nanoparticles, the study of their structure is a major step towards understanding the mechanisms of their interaction with biological environment. Detailed structural analysis of particles' surface is vital for rational design of drug delivery systems. In particular, for core-shell or surface-modified nanoparticles surface structure can be described in terms of shell coating uniformity and shell thickness uniformity around the nanoparticle core. Taken together, these terms can be used to indicate degree of heterogeneity of nanoparticle surface structure. However, characterization of nanoparticle surface structure under physiological conditions is challenging due to limitations of experimental techniques. In this paper, we apply SAXS contrast variation combined with ab initio bead modeling for this purpose. Approach is based on the fact that nanoparticles under study are produced by self-assembly of phospholipid-conjugated molecules that possess moieties with significantly different electron densities enabling SAXS technique to be used to distinguish nanoparticle shell and study its structure. Ab initio single phase and ab initio multiphase modeling based on SAXS curve of nanoparticles in phosphate buffer solution allowed to reconstruct nanoparticle shell coating and assess its uniformity, while serial nanoparticle reconstructions from solutions with gradually increased solvent electron densities revealed relative shell coating thickness around nanoparticle core. Nanoparticle shell structure representation was verified by molecular dynamics simulation and derived full-atom nanoparticle shell structure showed good agreement with SAXS-derived representation. Obtained data indicate that studied nanoparticles exhibit highly heterogeneous surface structure.
对于纳米颗粒的生物医学应用而言，研究其结构是理解它们与生物环境相互作用机制的重要一步。对颗粒表面进行详细的结构分析对于合理设计药物递送系统至关重要。特别是对于核壳型或表面改性的纳米颗粒，其表面结构可以通过纳米颗粒核心周围的壳层涂层均匀性和壳层厚度均匀性来描述。综合起来，这些术语可用于指示纳米颗粒表面结构的异质性程度。然而，由于实验技术的限制，在生理条件下表征纳米颗粒表面结构具有挑战性。在本文中，我们为此应用了小角X射线散射（SAXS）对比变化结合从头算珠子建模的方法。该方法基于这样一个事实，即所研究的纳米颗粒是由磷脂共轭分子自组装产生的，这些分子具有电子密度显著不同的部分，使得SAXS技术能够用于区分纳米颗粒壳层并研究其结构。基于磷酸盐缓冲溶液中纳米颗粒的SAXS曲线进行的从头算单相和从头算多相建模，能够重建纳米颗粒壳层涂层并评估其均匀性，而从溶剂电子密度逐渐增加的溶液中进行的系列纳米颗粒重建则揭示了纳米颗粒核心周围相对的壳层涂层厚度。通过分子动力学模拟验证了纳米颗粒壳层结构表示，并且推导得到的全原子纳米颗粒壳层结构与SAXS推导的表示显示出良好的一致性。获得的数据表明所研究的纳米颗粒呈现出高度异质的表面结构。
