title: Bio-active engineered 50 nm 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.
authors: Emory University, Department of Medicine, Division of Endocrinology, Metabolism and Lipids, Atlanta, GA 30322, USA.
authors: Shin-Woo
authors: SW
authors: Ha
authors: Medicinal Chemistry & Drug Discovery, 421 Shetland Valley Ct., Chesterfield, MO 63005, USA.
authors: James A
authors: JA
authors: Sikorski
authors: Emory University, Department of Medicine, Division of Endocrinology, Metabolism and Lipids, Atlanta, GA 30322, USA; The Atlanta Department of Veterans Affairs Medical Center, Decatur, GA 30033, USA; The Winship Cancer Institute, Emory University School of Medicine, Atlanta, GA 30322, USA. Electronic address: mweitzm@emory.edu.
authors: M Neale
authors: MN
authors: Weitzmann
authors: Emory University, Department of Medicine, Division of Endocrinology, Metabolism and Lipids, Atlanta, GA 30322, USA; The Atlanta Department of Veterans Affairs Medical Center, Decatur, GA 30033, USA; The Winship Cancer Institute, Emory University School of Medicine, Atlanta, GA 30322, USA. Electronic address: george.beck@emory.edu.
authors: George R
authors: GR
authors: Beck
mesh_terms: D000818:Animals; D001847:Bone Diseases / Q000188:drug therapy / Q000473:pathology; D002460:Cell Line; D006801:Humans; D020128:Inhibitory Concentration 50; D008280:Magnetics; D059630:Mesenchymal Stem Cells / Q000187:drug effects / Q000378:metabolism; D053758:Nanoparticles; D010006:Osteoblasts / Q000187:drug effects / Q000378:metabolism; D010010:Osteoclasts / Q000187:drug effects / Q000378:metabolism; D010316:Particle Size; D011092:Polyethylene Glycols / Q000737:chemistry*; D012822:Silicon Dioxide / Q000008:administration & dosage / Q000494:pharmacology* / Q000633:toxicity; D018675:Toxicity Tests / Q000379:methods
chemical_list: D011092:Polyethylene Glycols; D012822:Silicon Dioxide
keywords: Bone; Osteoblasts; Osteoclasts; Silica nanoparticles; Therapeutic index; Toxicity