Mesoporous silica nanoparticles surrounded by a lipid bilayer: Absence of in vitro hemonanotoxicity

Nanomedicine aims at rising innovative tools in order to improve the diagnosis and the therapy of human diseases. The development of robust theranostic nanomaterials displaying treatment efficiency and reduction of detrimental... [ view full abstract ]

Nanomedicine aims at rising innovative tools in order to improve the diagnosis and the therapy of human diseases. The development of robust theranostic nanomaterials displaying treatment efficiency and reduction of detrimental side effect to normal tissues will deeply improve patient quality of life. Due to their size and versatile character nanoparticles can pass through the physiological barriers and deliver medicines. Therefore, the translation process of these new therapeutic nanocarriers to their clinical use relies on their interaction with the physiological environment.
Following the synthesis and the complete physicochemical characterization of a 55 nm mesoporous silica nanoparticle surrounded by a lipid bilayer (55 nm MSNP@SLB), we have evaluated its susceptibility for safely intravenous administration. In a first step of in vitro experimentation on red blood cells (RBCs), Scanning Electron Microscopy and hemolysis assay have shown no deformation and disruption of their membrane. No cytotoxic effect was neither observed on Peripheral Blood Mononuclear and on Human Marrow Stromal cells (HS-5 cell line).
We have therefore elaborated our nanoparticle study with the determination of coagulation parameters i.e. Prothrombin Time (PT) and Activated Partial Thromboplastin Time (APTT). These Nanoparticles display values in a normal range without formation of a clot. These results are in correlation with no platelets activation and aggregation.
Using scanning confocal microscopy, we observed that isolated RBCs that have been in contact with nanoparticles surrounded by a lipid bilayer are not cleared by activated macrophages (THP-1). This phenomenon is correlated with the absence of phosphatidylserine externalization on RBCs membrane. The activated macrophage model incubated with the nanoparticles of interest showed uptake of nanoparticles and did not trigger ROS production.
In conclusion, the nanoparticle under development displays no in vitro toxic effects in the major cellular components of blood and the development of this multiphased nanoplatform should result in a biocompatible theranostic tool.