Molecular Mechanisms of the Interactions of N-(2-Hydroxypropyl)methacrylamide Copolymers Designed for Cancer Therapy with Blood Plasma Proteins.

Larisa Janisova,Petr Chytil,Dmitri I Svergun,Olga Janoušková,Xiaohan Zhang,Ondřej Vaněk,Andrey Gruzinov,Christine M Papadakis,Clement Blanchet,Sergey K Filippov,Nadiia Velychkivska,Tomáš Etrych,Olga V Zaborova

doi:10.3390/pharmaceutics12020106

Abstract

The binding of plasma proteins to a drug carrier alters the circulation of nanoparticles (NPs) in the bloodstream, and, as a consequence, the anticancer efficiency of the entire nanoparticle drug delivery system. We investigate the possible interaction and the interaction mechanism of a polymeric drug delivery system based on N-(2-hydroxypropyl)methacrylamide (HPMA) copolymers (pHPMA) with the most abundant proteins in human blood plasma—namely, human serum albumin (HSA), immunoglobulin G (IgG), fibrinogen (Fbg), and apolipoprotein (Apo) E4 and A1—using a combination of small-angle X-ray scattering (SAXS), analytical ultracentrifugation (AUC), and nuclear magnetic resonance (NMR). Through rigorous investigation, we present evidence of weak interactions between proteins and polymeric nanomedicine. Such interactions do not result in the formation of the protein corona and do not affect the efficiency of the drug delivery.

Highlights

The design of anticancer therapeutics is focused on creating new systems with low toxicity, e.g., those based on nanocarriers, enabling targeted delivery and high efficiency of the treatment [1]
We investigate the possible interaction and the interaction mechanism of a polymeric drug delivery system based on N-(2-hydroxypropyl)methacrylamide (HPMA) copolymers with the most abundant proteins in human blood plasma—namely, human serum albumin (HSA), immunoglobulin G (IgG), fibrinogen (Fbg), and apolipoprotein (Apo) E4 and A1—using a combination of small-angle X-ray scattering (SAXS), analytical ultracentrifugation (AUC), and nuclear magnetic resonance (NMR)
We found that no protein corona was formed by human serum albumin (HSA) around the pHPMA-based NPs, and only a weak interaction between the HSA and NPs was detected using small-angle X-ray scattering (SAXS)

Summary

Introduction

The design of anticancer therapeutics is focused on creating new systems with low toxicity, e.g., those based on nanocarriers, enabling targeted delivery and high efficiency of the treatment [1]. We investigate the possible interaction and the interaction mechanism of a polymeric drug delivery system based on N-(2-hydroxypropyl)methacrylamide (HPMA) copolymers (pHPMA) with the most abundant proteins in human blood plasma—namely, human serum albumin (HSA), immunoglobulin G (IgG), fibrinogen (Fbg), and apolipoprotein (Apo) E4 and A1—using a combination of small-angle X-ray scattering (SAXS), analytical ultracentrifugation (AUC), and nuclear magnetic resonance (NMR).

Results

Conclusion