Influence of Geometry, Porosity, and Surface Characteristics of Silica Nanoparticles on Acute Toxicity: Their Vasculature Effect and Tolerance Threshold

Abstract

Silica nanoparticles (SiO2) are widely used in biomedical applications such as drug delivery, cell tracking and gene transfection. The capability to control the geometry, porosity, and surface characteristics of SiO2 further provides new opportunities for their applications in nanomedicine. Concerns however remain about the potential toxic effects of SiO2 upon exposure to biological systems. In the present study, the acute toxicity of SiO2 of systematically varied geometry, porosity and surface characteristics was evaluated in immune-competent mice when administered intravenously. Results suggest that in vivo toxicity of SiO2 was mainly influenced by nanoparticle porosity and surface characteristics. The maximum tolerated dose (MTD) increased in the following order: Mesoporous SiO2 (aspect ratio 1, 2, 8) at 30 – 65 mg/kg < amine-modified mesoporous SiO2 (aspect ratio 1, 2, 8) at 100 – 150 mg/kg < unmodified or amine-modified nonporous SiO2 at 450 mg/kg. The adverse reactions above MTDs were primarily caused by the mechanical obstruction of SiO2 in the vasculature that led to congestion in multiple vital organs and subsequent organ failure. It was revealed that hydrodynamic sizes of SiO2 post protein exposure had an important implication in relating SiO2 physicochemical properties with their vasculature impact and resultant tolerance threshold, as the larger the hydrodynamic size in the presence of serum protein, the lower the MTD. This study sheds light on the rational design of SiO2 to minimize in vivo toxicity and provides a critical guideline in selecting SiO2 as the appropriate system for nanomedicine applications.

Pluronic polymer capped biocompatible mesoporous silica nanocarriers

“…However, recent studies demonstrated their potential in vitro and in vivo toxicity, especially when their size is reduced to the nano scale. 3,4 Although the toxicity of silica based nanomaterials depends on several factors including particle size, shape, surface chemistry and porosity, [5][6][7] there is a general consensus that chemical structure of the surface is the predominant factor which determines the interactions with biological systems. 8 The surface of bare silica is covered with negatively charged silanol groups, which can electrostatically interact with positively charged tetraalkylammonium moieties of the cell membrane and can lead to cytotoxicity by membranolysis or inhibition of cellular respiration.…”

Polymeric nanoparticles for optical sensing

“…Considering their biocompatibility, SNPs have been also employed as carriers for NIR dyes for in vivo imaging of mouse bladder (Burns et al, 2009), and for specific tumor imaging (Benezra et al, 2011). The main factors which affect the acute toxicity of SNPs include shape, porosity and their surface characteristics (Nakamura et al, 2007, Yu et al, 2012. These latter affect also the colloidal stability of nanosystems in vivo, which might agglomerate and determine an immune response.…”

Conjugation of glucosamine with Gd3+-based nanoporous silica using a heterobifunctional ANB-NOS crosslinker for imaging of cancer cells

“…4 Briefly, 1.0 g of cetyltrimethylammonium bromide was dissolved in 500 mL of distilled water containing 3.5 mL of 2 M NaOH, and the solution was heated to 80°C. Next, 5.0 mL of tetraethylorthosilicate was added to the mixture.…”

“…Numerous studies of the biocompatibility and toxicity of MSNs have been reported. [1][2][3][4] MSNs have a high surface area and large pore volumes for pay loading of magnetic centers and tunable particle size for efficient cellular uptake. [5][6][7][8][9][10][11] There has been interest in developing smart MSN nanocarriers with external and internal surfaces that can be selectively functionalized with multiple groups.…”