Implications of protein corona on physico-chemical and biological properties of magnetic nanoparticles

Abstract

Interaction of serum proteins and nanoparticles leads to a nanoparticle-protein complex formation that defines the rational strategy for a clinically relevant formulation for drug delivery, hyperthermia, and magnetic resonance imaging (MRI) applications in cancer nanomedicine. Given this perspective, we have examined the pattern of human serum protein corona formation with our recently engineered magnetic nanoparticles (MNPs). The alteration in particle size, zeta potential, hemotoxicity, cellular uptake/cancer cells targeting potential, and MRI properties of the MNPs after formation of human serum (HS) protein corona were studied. Our results indicated no significant change in particle size of our MNPs upon incubation with 0.5-50 wt/v% human serum, while zeta potential of MNPs turned negative due to human serum adsorption. When incubated with an increased serum and particle concentration, apolipoprotein E was adsorbed on the surface of MNPs apart from serum albumin and transferrin. However, there was no significant primary or secondary structural alterations observed in serum proteins through Fourier transform infrared spectroscopy, X-ray diffraction, and circular dichroism. Hemolysis assay suggests almost no hemolysis at the tested concentrations (up to 1 mg/mL) for MNPs compared to the sodium dodecyl sulphate (positive control). Additionally, improved internalization and uptake of MNPs by C4-2B and Panc-1 cancer cells were observed upon incubation with human serum (HS). After serum protein adsorption to the surface of MNPs, the close vicinity within T1 (~1.33-1.73 s) and T2 (~ 12.35-13.43 ms) relaxation times suggest our MNPs retained inherent MRI potential even after biomolecular protein adsorption. All these superior clinical parameters potentially enable clinical translation and use of this formulation for next generation nanomedicine for drug delivery, cancer-targeting, imaging and theranostic applications.

Impact of silica nanoparticle surface chemistry on protein corona formation and consequential interactions with biological cells

“…Due to the discrepancy in the published results, the relationship between protein adsorption on NP and the decrease of the cellular internalization of NP remains to be established. Indeed, some studies show that protein adsorption on NP decreases their cellular uptake while other tend to demonstrate the opposite [18,19,25,[29][30][31][32]. Furthermore, it is difficult to draw firm conclusions from results dealing with different NP types, different functionalization groups, different cellular models, different biological assays, etc.…”

Protein corona: a new approach for nanomedicine design

“…It could be considered as the major proteins on the magnetic NP at 50% serum concentration. 36 In contrast, phagocytosis of NPs by dendritic cells was identical in various concentrations of protein mixtures. This result could be explained by particle uptake by phagocytes, possibly not dependent on the total binding protein quantity but the abundance of recognizable proteins on the particle surface.…”

Comparative toxicity and biodistribution of copper nanoparticles and cupric ions in rats

“…4,42 In addition, physiological milieus influence the interaction of biological systems with NPs and can determine the fate and biosafety of NPs. 7 Thus, comprehensive characterization of the NPs in physiological conditions is a fundamental step prior to assessing the in vivo toxicity of Cu NPs. The hydrodynamic diameter and zeta potential of Cu NPs indicated that Cu NPs have a tendency to aggregate/agglomerate in vehicle (pH 6.5) and simulated intestinal (pH 7.8) conditions.…”

“…5,6 Furthermore, the physiological milieu influences the interaction between biological systems and NPs and can determine the fate and biosafety of NPs. 7 Currently, with the widespread use of NPs, health risks and environmental effects related to NP exposure have become of great concern. 8 In addition, the applications of NPs have been limited by lack of verification of biosafety.…”