Biosafety of Mesoporous Silica Nanoparticles.

Estelle Rascol,Morgane Daurat,Afitz Silva,Magali Gary-Bobo,Marcel Garcia,Joël Chopineau,Clarence Charnay,Jean Armengaud,Yannick Guari,Jean-Charles Gaillard,Christophe Dorandeu,Jean-Marie Devoisselle,Marie Maynadier,Jeff Nyalosaso,Odette Prat,Cédric Pisani

doi:10.3390/biomimetics3030022

Abstract

Careful analysis of any new nanomedicine device or disposal should be undertaken to comprehensively characterize the new product before application, so that any unintended side effect is minimized. Because of the increasing number of nanotechnology-based drugs, we can anticipate that regulatory authorities might adapt the approval process for nanomedicine products due to safety concerns, e.g., request a more rigorous testing of the potential toxicity of nanoparticles (NPs). Currently, the use of mesoporous silica nanoparticles (MSN) as drug delivery systems is challenged by a lack of data on the toxicological profile of coated or non-coated MSN. In this context, we have carried out an extensive study documenting the influence of different functionalized MSN on the cellular internalization and in vivo behaviour. In this article, a synthesis of these works is reviewed and the perspectives are drawn. The use of magnetic MSN (Fe3O4@MSN) allows an efficient separation of coated NPs from cell cultures with a simple magnet, leading to results regarding corona formation without experimental bias. Our interest is focused on the mechanism of interaction with model membranes, the adsorption of proteins in biological fluids, the quantification of uptake, and the effect of such NPs on the transcriptomic profile of hepatic cells that are known to be readily concerned by NPs’ uptake in vivo, especially in the case of an intravenous injection.

Highlights

The growing interest of the scientific community for mesoporous silica nanoparticles (MSN) is related to the degree of advanced sophistication that can be achieved in their design according to the objectives, in terms of properties or applications sought
The formation of a protein corona appeared to reduce the interaction between MSN and model membranes composed of an egg phosphatidylcholine (EPC)-supported lipid bilayer (SLB) as was observed using quartz crystal microbalance with dissipation (QCM-D) [4] (Figure 4b)
Fe3 O4 @MSN was faster for those that were coated with dimyristoyl phosphatidylcholine (DMPC) than for the native ones, and slower after exposure of HepG2 (Figure 6) and HepaRG cell lines to Fe3O4@MSN [6]

Summary

Introduction

The growing interest of the scientific community for mesoporous silica nanoparticles (MSN) is related to the degree of advanced sophistication that can be achieved in their design according to the objectives, in terms of properties or applications sought. Biomimetics 2018, 3, 22 chemistry, these nanoparticles (NPs) have a promising potential to constitute a new generation of smart drug nanocontainers, due to their high stability, large surface area, tunable pore size, and abundant surface functionalization sites [1,2]. For these reasons, MSN are one of the most studied nanotechnologies for use as drug delivery systems. In vitro studies at the molecular and cellular level allow for rapid knowledge generation, and their results could be used as predictors before a validation phase, in terms of toxicological outcome in vivo This two-stage approach could limit the extent, volume, and cost of animal testing. Our interest focuses on MSN’s interaction with model membranes [4], the adsorption of proteins at their surface in biological fluids [5], the kinetics of internalization, and the effect of such NPs on the transcriptomic profile of hepatic cells [6] that are known to be readily concerned by NPs’ uptake in vivo, especially in the case of an intravenous injection

Preparation of Magnetic Mesoporous Silica Nanoparticles

Magnetic

Ovitro

Canonical pathways elicited bymajor eachaltered

Conclusions