Bio-active engineered 50nm silica nanoparticles with bone anabolic activity: Therapeutic index, effective concentration, and cytotoxicity profile in vitro

Abstract

Silica-based nanomaterials are generally considered to be excellent candidates for therapeutic applications particularly related to skeletal metabolism however the current data surrounding the safety of silica based nanomaterials is conflicting. This may be due to differences in size, shape, incorporation of composite materials, surface properties, as well as the presence of contaminants following synthesis. In this study we performed extensive in vitro safety profiling of ~50 nm spherical silica nanoparticles with OH-terminated or Polyethylene Glycol decorated surface, with and without a magnetic core, and synthesized by the Stöber method. Nineteen different cell lines representing all major organ types were used to investigate an in vitro lethal concentration (LC) and results revealed little toxicity in any cell type analyzed. To calculate an in vitro therapeutic index we quantified the effective concentration at 50% response (EC50) for nanoparticle-stimulated mineral deposition activity using primary bone marrow stromal cells (BMSCs). The EC50 for BMSCs was not substantially altered by surface or magnetic core. The calculated Inhibitory concentration 50% (IC50) for pre-osteoclasts was similar to the osteoblastic cells. These results demonstrate the pharmacological potential of certain silica-based nanomaterial formulations for use in treating bone diseases based on a favorable in vitro therapeutic index.

Influence of needle-like morphology on the bioactivity of nanocrystalline wollastonite – an in vitro study

“…Wollastonite is expected to induce osteogenesis by satisfying all these criteria, hence it can be used as an artificial bone implant material. 19,20 The various synthetic methods employed for the preparation of wollastonite are solid-state, 21 hydrothermal, 22 coprecipitation, 23 and solution combustion synthesis. 24 The most widely used method for the preparation of wollastonite is the sol-gel method, as the synthesized particles are homogeneous and the particles were found to be in the nano-regime.…”

Synthesis of pH stable, blue light-emitting diode-excited, fluorescent silica nanoparticles and effects on cell behavior

“…Cell viability was measured using a commercial 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxyl-methoxyphenyl)-2-(4-sulfonyl)-2H-tetrazolium (XTT) assay according to the manufacturer's protocol (Promega Corporation, Fitchburg, WI, USA) as described previously. 6 Cells were plated at ~5×10 3 cells/well (~50%-60% confluent) in 96-well plates. After 24 hours, NPs were added as indicated, and 3 days later, the cells were analyzed using XTT (20 µL in 100 µL) assay reagent on a spectrophotometer (SpectraMAX250; Molecular Devices LLC, Sunnyvale, CA, USA).…”

“…The NPs are located in cytoplasm but not in the nucleus in agreement with previous studies using red-fluorescent 50 nm silica-based NPs. 6,13,36 Spherical 50 nm silica NPs have been demonstrated to be internalized by most cell types and from varying origins, 6 and it is therefore expected that LEDex NPs will also act in a similar manner. Taken together, the results demonstrate that these LEDex NPs can be used as a novel cell imaging agent.…”

“…Silica nanoparticles (NPs) have many potential applications in biology and biomedicine because of important physical characteristics such as biocompatibility, 6,7 the ability to precisely control size and shape, color tunability, and photostability when combined with imaging agents. [8][9][10] Silicon dioxide (SiO 2 ) materials lack any emission property, and therefore, the excitation wavelength is dependent upon the incorporated dyes.…”

Effects of Silica Nanoparticles on Rat Cortical Bone Biomechanics: Experimental Study

“…Ha ve ark.nın, MC3T3-E1 hücre hatlarında yaptıkları bir başka çalışmada, 50 nm SiO 2 nanoparçacıklarının osteoblast farklılaş-masını artırdığı bildirilmiştir. 25 Weitzmann ve ark.nın, 50 nm boyutunda SiO 2 nanoparçacıklarını kullanarak yaşlı farelerde yaptıkları bir başka çalış-mada bu nanoparçacıkların kemik kaybını önlediği öne sürülmüştür. 26 Çalışmamızda ise 6 nm boyutundaki SiO 2 nanoparçacıklarının kemik biyomekanik kalitesini bozarak kemiğin kırılganlığını artırdığı gözlenmiştir.…”