4.7 Article

Impact of particle size and pH on protein corona formation of solid lipid nanoparticles: A proof-of-concept study

Journal

ACTA PHARMACEUTICA SINICA B
Volume 11, Issue 4, Pages 1030-1046

Publisher

INST MATERIA MEDICA, CHINESE ACAD MEDICAL SCIENCES
DOI: 10.1016/j.apsb.2020.10.023

Keywords

Protein corona; Solid lipid nanoparticles; BSA corona-Caused aggregation; Nanoparticle-protein interaction; Size effect; Cell uptake; Medium pH; Conformational structure

Funding

  1. National Natural Science Foundation of China [81703431, 81673375]
  2. Natural Science Fund Project of Guangdong Province [2016A030312013]
  3. AutoDock molecular docking technique

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This study investigates the influence of particle size and pH on the formation of protein corona on solid lipid nanoparticles (SLNs). It reveals that the protein corona significantly affects the secondary structure of proteins and cell uptake of nanoparticles, with the main interaction driven by factors like van der Waals forces, hydrogen bonding, and electrostatic attraction depending on the pH and size.
When nanoparticles were introduced into the biological media, the protein corona would be formed, which endowed the nanoparticles with new bio-identities. Thus, controlling protein corona formation is critical to in vivo therapeutic effect. Controlling the particle size is the most feasible method during design, and the influence of media pH which varies with disease condition is quite important. The impact of particle size and pH on bovine serum albumin (BSA) corona formation of solid lipid nanoparticles (SLNs) was studied here. The BSA corona formation of SLNs with increasing particle size (120-480 nm) in pH 6.0 and 7.4 was investigated. Multiple techniques were employed for visualization study, conformational structure study and mechanism study, etc. BSA corona-caused aggregation of SLN2-3 was revealed in pH 6.0 while the dispersed state of SLNs was maintained in pH 7.4, which significantly affected the secondary structure of BSA and cell uptake of SLNs. The main interaction was driven by van der Waals force plus hydrogen bonding in pH 7.4, while by electrostatic attraction in pH 6.0, and size-dependent adsorption was confirmed. This study provides a systematic insight to the understanding of protein corona formation of SLNs. (C) 2021 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V.

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