Abstract

The biological fate of nanoparticles (NPs) for biomedical applications is highly dependent of their size and charge, their aggregation state and their surface chemistry. The chemical composition of the NPs surface influences their stability in biological fluids, their interaction with proteins, and their attraction to the cell membranes. In this work, core-shell magnetic mesoporous silica nanoparticles (Fe3O4@MSN), that are considered as potential theranostic candidates, are coated with polyethylene glycol (PEG) or 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) lipid bilayer. Their biological fate is studied in comparison to the native NPs. The physicochemical properties of these three types of NPs and their suspension behavior in different media are investigated. The attraction to a membrane model is also evaluated using a supported lipid bilayer. The surface composition of NPs strongly influences their dispersion in biological fluids mimics, protein binding and their interaction with cell membrane. While none of these types of NPs is found to be toxic on mice four days after intravenous injection of a dose of 40 mg kg−1 of NPs, their surface coating nature influences the in vivo biodistribution. Importantly, NP coated with DMPC exhibit a strong accumulation in liver and a very low accumulation in lung in comparison with nude or PEG ones.

Highlights

  • In the past two decades, nanoparticles (NPs) for medical applications have been investigated by numerous researchers

  • The presented data demonstrate that native, DMPC and polyethylene glycol (PEG) Fe3O4@Mesoporous Silica Nanoparticles (MSN) stay dispersed and stable during 15 h when diluted in a medium having a low ionic strength (HBS 5 mM NaCl, pH 7.4)

  • PEG Fe3O4@MSN are aggregated when diluted in HBS 150 mM NaCl, pH 7.4, in the presence or in the absence of proteins, or in RPMI containing SVF 10% and slowly dispersed in the presence of proteins

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Summary

Introduction

In the past two decades, nanoparticles (NPs) for medical applications have been investigated by numerous researchers. The NPs based theranostic agents combine, in a unique formulation, tracking, imaging, diagnosis, cell-targeting and drug delivery properties In this emerging field of nanomedicine, Mesoporous Silica Nanoparticles (MSN) are considered as a promising platform for drug-delivery and cell targeting [1]. Water molecules interact via hydrogen bonds with the PEG moieties, enhancing the hydrodynamic diameter of the NPs [12] This type of grafting induces aggregation in high saline concentration solution [14]. If the quantity was not optimized, PEG grafting did not improve colloidal stability [15] Another strategy to produce a stealth effect, less investigated than the PEG coating, is to coat the surface of NPs with a lipid bilayer. An early effect of DMPC Fe3O4@MSN on cells has been observed using real-time dependent impedance measurements translating the difference in cell morphologies after NPs treatments

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