SiO₂nanoparticles biocompatibility and their potential for gene delivery and silencing

Abstract

Despite the extensive use of silica nanoparticles (SiO(2)NPs) in many fields, the results about their potential toxicity are still controversial. In this work, we have performed a systematic in vitro study to assess the biological impact of SiO(2)NPs, by investigating 3 different sizes (25, 60 and 115 nm) and 2 surface charges (positive and negative) of the nanoparticles in 5 cell lines (3 in adherence and 2 in suspension). We analyzed the cellular uptake and distribution of the NPs along with their possible effects on cell viability, membrane integrity and generation of reactive oxygen species (ROS). Experimental results show that all the investigated SiO(2)NPs do not induce detectable cytotoxic effects (up to 2.5 nM concentration) in all cell lines, and that cellular uptake is mediated by an endocytic process strongly dependent on the particle size and independent of its original surface charge, due to protein corona effects. Once having assessed the biocompatibility of SiO(2)NPs, we have evaluated their potential in gene delivery, showing their ability to silence specific protein expression. The results of this work indicate that monodisperse and stable SiO(2)NPs are not toxic, revealing their promising potential in various biomedical applications.

In vitro cytotoxicity of SiO2 or ZnO nanoparticles with different sizes and surface charges on U373MG human glioblastoma cells

“…[28][29][30][31] Consistent with these studies, we observed that particle size affected the cytotoxicity of SiO 2 EN20(R) and SiO 2 EN20(−) NPs, which were, respectively, eleven-and sevenfold more toxic than 100 nm counterparts against U373MG …”

Nanoparticle accumulation and transcytosis in brain endothelial cell layers

“…SiO 2 nanoparticles of different sizes are known to enter cells by active transport 59,60 and were used here to test the blood-brain barrier model, in order to investigate the cellular interactions of the nanoparticles and look for potential evidence of transcytosis. Particle characterisation in assay medium containing 2 % foetal bovine serum (FBS) indicated that 50 nm (nominal diameter) SiO 2 nanoparticles were partially agglomerated when exposed to cells (See Supplementary Table S1).…”

Silica nanoparticles induce oxidative stress, inflammation, and endothelial dysfunction in vitro via activation of the MAPK/Nrf2 pathway and nuclear factor-κB signaling

“…Malvindi et al pointed out that SiNPs had good biocompatibility when used in a reasonable concentration range (up to 2.5 nM). 7 However, as they are smaller than cellular organelles, it is increasingly recognized that SiNPs could penetrate the cytomembrane, deposit in mitochondria or even the nucleus, and eventually lead to cell death. [8][9][10][11] It has been confirmed that NPs can systemically translocate to the circulation from the lung.…”