Biological Fate of Fe3O4 Core-Shell Mesoporous Silica Nanoparticles Depending on Particle Surface Chemistry

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.

Biocompatibility assessment of functionalized magnetic mesoporous silica nanoparticles in human HepaRG cells

“…Three concentrations to be tested were chosen for all types of NPs, that is 1.6, 16, and 80 mg/cm 2 (corresponding to 6, 60, and 300 mg/mL, respectively) in accordance with both literature and our viability assays data (Hudson et al 2008;Witasp et al 2009). In particular, this choice was based on the concentration of 40 mg/kg already used for biodistribution studies by injection in mice (Lu et al 2010;Liu et al 2011;Rascol et al, 2017). One milligram per mouse of 25 g with 2 mL of blood corresponds approximately to a concentration of 500 mg/ mL.…”

“…The dose 16 lg/cm 2 probably triggers the onset of effects that are more clearly observable with a higher dose. Despite the fact that no tissue alteration was observed at a higher dose in mice with M-MSN (Rascol et al 2017), an in-depth study at 80 mg/cm 2 could then reflect a predictive fate of HepaRG cells under exposure to M-MSNs.…”

“…Indeed, investigation of the in vivo biodistribution of functionalized MSNs has shown that the majority are observed in the liver and spleen (Liu et al 2011;Rascol et al 2017), with most of the Si injected into mice excreted in the urine and feces (94%) (Lu et al 2010).…”

A health concern regarding the protein corona, aggregation and disaggregation

“…As shown in Figure 1, proteins can alter their structures when binding to NPs and these NP induced conformation changes are determined by the physiochemical NP surface features, and the pH of the medium. In recent years, several studies explained dimension and surface morphology-dependent protein conformational changes induced by nanomaterials [37][38][39][40][41]. However, the outcomes of these studies were inconclusive.…”

Bidisperse Magnetic Particles Coated with Gelatin and Graphite Oxide: Magnetorheology, Dispersion Stability, and the Nanoparticle-Enhancing Effect

“…Recently, it was reported that the filling with nanoparticles was an effective method to reduce the sedimentation of larger particles in MR fluids [12,13,14,15,16,17,18,19,20]. Leong et al [21] prepared bidisperse magnetic particles (BMP) composed of γ -Fe 2 O 3 nanoparticles with an average size of 9 nm and carbonyl iron (CI) particles to investigate the rheological properties and sedimentation rate of the MR fluids.…”