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

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          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.

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          Author and article information

          Journal
          Toxicol In Vitro
          Toxicology in vitro : an international journal published in association with BIBRA
          1879-3177
          0887-2333
          Apr 2014
          : 28
          : 3
          Affiliations
          [1 ] Emory University, Department of Medicine, Division of Endocrinology, Metabolism and Lipids, Atlanta, GA 30322, USA.
          [2 ] Medicinal Chemistry & Drug Discovery, 421 Shetland Valley Ct., Chesterfield, MO 63005, USA.
          [3 ] 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.
          [4 ] 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.
          Article
          S0887-2333(13)00318-4 NIHMS549880
          10.1016/j.tiv.2013.12.001
          3926416
          24333519
          6aae6bc4-cf25-458b-8108-de09e703754a
          Copyright © 2013 Elsevier Ltd. All rights reserved.
          History

          Bone,Osteoblasts,Osteoclasts,Silica nanoparticles,Therapeutic index,Toxicity

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