Issue 17, 2021

Electrokinetic elucidation of the interactions between persistent luminescent nanoprobes and the binary apolipoprotein-E/albumin protein system

Abstract

The affinity between functional nanoparticles (NPs) and proteins could determine the efficacy of nanoprobes, nanosensors, nanocarriers, and many other devices for biomedical applications. Therefore, it is necessary to develop analytical strategies to accurately evaluate the magnitude of these protein corona interactions in physiological media. In this work, different electrokinetic strategies were implemented to accurately determine the interactions between PEGylated ZnGa1.995Cr0.005O4 persistent luminescent NPs (ZGO-PEG) and two important serum proteins: human serum albumin (HSA), the most abundant serum protein, and apolipoprotein-E (ApoE), associated with the active transport of NPs through the blood–brain barrier. Firstly, the injection of ZGO-PEG in a background electrolyte (BGE) containing individual proteins allowed an affinity study to separately characterize each NP–protein system. Then, the same procedure was applied in a buffer containing a mixture of the two proteins at different molar ratios. Finally, the NPs were pre-incubated with one protein and thereafter electrokinetically separated in a BGE containing the second protein. These analytical strategies revealed the mechanisms (comparative, cooperative or competitive systems) and the magnitude of their interactions, resulting in all cases in notably higher affinity and stability between ZGO-PEG and ApoE (Ka = 1.96 ± 0.25 × 1010 M−M) compared to HSA (Ka = 4.60 ± 0.41 × 106 M−M). For the first time, the inter-protein ApoE/HSA interactions with ZGO-PEG were also demonstrated, highlighting the formation of a ternary ZGO-PEG/ApoE/HSA nanocomplex. These results open the way for a deeper understanding of the protein corona formation, and the development of versatile optical imaging applications for ZGO-PEG and other systemically delivered nanoprobes ideally vectorized to the brain.

Graphical abstract: Electrokinetic elucidation of the interactions between persistent luminescent nanoprobes and the binary apolipoprotein-E/albumin protein system

Supplementary files

Article information

Article type
Paper
Submitted
03 מאי 2021
Accepted
05 יול 2021
First published
05 יול 2021

Analyst, 2021,146, 5245-5254

Electrokinetic elucidation of the interactions between persistent luminescent nanoprobes and the binary apolipoprotein-E/albumin protein system

G. Ramírez García, F. d'Orlyé, C. Richard, N. Mignet and A. Varenne, Analyst, 2021, 146, 5245 DOI: 10.1039/D1AN00781E

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