Issue 13, 2018

Interaction of spin-labeled HPMA-based nanoparticles with human blood plasma proteins – the introduction of protein-corona-free polymer nanomedicine

Abstract

In this paper, we revised the current understanding of the protein corona that is created on the surface of nanoparticles in blood plasma after an intravenous injection. We have focused on nanoparticles that have a proven therapeutic outcome. These nanoparticles are based on two types of biocompatible amphiphilic copolymers based on N-(2-hydroxypropyl)methacrylamide (HPMA): a block copolymer, poly(ε-caprolactone) (PCL)-b-poly(HPMA), and a statistical HPMA copolymer bearing cholesterol moieties, which have been tested both in vitro and in vivo. We studied the interaction of nanoparticles with blood plasma and selected blood plasma proteins by electron paramagnetic resonance (EPR), isothermal titration calorimetry, dynamic light scattering, and cryo-transmission electron microscopy. The copolymers were labeled with TEMPO radicals at the end of hydrophobic PCL or along the hydrophilic HPMA chains to monitor changes in polymer chain dynamics caused by protein adsorption. By EPR and other methods, we were able to probe specific interactions between nanoparticles and blood proteins, specifically low- and high-density lipoproteins, immunoglobulin G, human serum albumin (HSA), and human plasma. It was found that individual proteins and plasma have very low binding affinity to nanoparticles. We observed no hard corona around HPMA-based nanoparticles; with the exception of HSA the proteins showed no detectable binding to the nanoparticles. Our study confirms that a classical “hard corona–soft corona” paradigm is not valid for all types of nanoparticles and each system has a unique protein corona that is determined by the nature of the NP material.

Graphical abstract: Interaction of spin-labeled HPMA-based nanoparticles with human blood plasma proteins – the introduction of protein-corona-free polymer nanomedicine

Supplementary files

Article information

Article type
Paper
Submitted
15 Dec 2017
Accepted
23 Feb 2018
First published
26 Feb 2018

Nanoscale, 2018,10, 6194-6204

Interaction of spin-labeled HPMA-based nanoparticles with human blood plasma proteins – the introduction of protein-corona-free polymer nanomedicine

D. Klepac, H. Kostková, S. Petrova, P. Chytil, T. Etrych, S. Kereïche, I. Raška, D. A. Weitz and S. K. Filippov, Nanoscale, 2018, 10, 6194 DOI: 10.1039/C7NR09355A

To request permission to reproduce material from this article, please go to the Copyright Clearance Center request page.

If you are an author contributing to an RSC publication, you do not need to request permission provided correct acknowledgement is given.

If you are the author of this article, you do not need to request permission to reproduce figures and diagrams provided correct acknowledgement is given. If you want to reproduce the whole article in a third-party publication (excluding your thesis/dissertation for which permission is not required) please go to the Copyright Clearance Center request page.

Read more about how to correctly acknowledge RSC content.

Social activity

Spotlight

Advertisements