Assessment of core-shell nanoparticles surface structure heterogeneity by SAXS contrast variation and ab initio modeling

I S Vaskan; A T Prikhodko; M V Petoukhov; E V Shtykova; N V Bovin; A B Tuzikov; V A Oleinikov; A V Zalygin

doi:10.1016/j.colsurfb.2023.113183

Assessment of core-shell nanoparticles surface structure heterogeneity by SAXS contrast variation and ab initio modeling

Colloids Surf B Biointerfaces. 2023 Apr:224:113183. doi: 10.1016/j.colsurfb.2023.113183. Epub 2023 Feb 2.

Authors

I S Vaskan¹, A T Prikhodko², M V Petoukhov³, E V Shtykova⁴, N V Bovin¹, A B Tuzikov¹, V A Oleinikov², A V Zalygin⁵

Affiliations

¹ Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow 117997, Russia.
² Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow 117997, Russia; National Research Nuclear University Moscow Engineering Physics Institute, Moscow 115409, Russia.
³ A.V. Shubnikov Institute of Crystallography of Federal Scientific Research Centre "Crystallography and Photonics" of the Russian Academy of Sciences, Moscow 119333, Russia; A.N. Frumkin Institute of Physical Chemistry and Electrochemistry of Russian Academy of Sciences, Moscow 119071, Russia.
⁴ A.V. Shubnikov Institute of Crystallography of Federal Scientific Research Centre "Crystallography and Photonics" of the Russian Academy of Sciences, Moscow 119333, Russia.
⁵ Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow 117997, Russia; National Research Nuclear University Moscow Engineering Physics Institute, Moscow 115409, Russia. Electronic address: zalygin.anton@gmail.com.

PMID: 36764203
DOI: 10.1016/j.colsurfb.2023.113183

Abstract

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.

Keywords: Lipid; MD; Nanoparticles; SAXS; Structural modeling; Surface heterogeneity.

MeSH terms

Drug Delivery Systems
Molecular Dynamics Simulation*
Nanoparticles* / chemistry
Scattering, Small Angle
X-Ray Diffraction