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

• Type of Material: Article
• Authors: Shin Ha, Emory University; James A. Sikorski, Medicinal Chemistry and Drug Discovery; M. Neale Weitzmann, Emory University; George Beck Jr, Emory University
• Language: English
• Date: 2014-04-01
• Publisher: Elsevier: 12 months
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2013 Elsevier Ltd.
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1016/j.tiv.2013.12.001
• Title of Journal or Parent Work: Toxicology in Vitro
• ISSN: 0887-2333
• Volume: 28
• Issue: 3
• Start Page: 354
• End Page: 364
• Grant/Funding Information: This study was supported by grants from NIAMS (AR056090); the Georgia Research Alliance (GRA.VL12.C2); and the Department of Biomedical Engineering at Georgia Institute of Technology; Emory University; and Children’s Healthcare of Atlanta, Center for Pediatric Nanomedicine, Atlanta, GA, USA (RC159-G3) to M.N. Weitzmann and G.R. Beck Jr. ;as well as Award Number I01BX002363 from the Biomedical Laboratory Research & Development Service of the VA Office of Research and Development to GR Beck Jr.; M.N. Weitzmann is also supported in part by funding from the Biomedical Laboratory Research & Development Service of the VA Office of Research and Development (5I01BX000105); and by grants AR059364 and AR053607 from NIAMS and AG040013 from NIA.; G.R. Beck is also supported in part by a grant from the NIH-NCI (CA136716).
• Keywords: DIFFERENTIATION; GENE-EXPRESSION; GROWTH; HEALTH; Silica nanoparticles; Osteoblasts; OSTEOBLAST-LIKE CELLS; Toxicity; DRUG; TOXICITY; PROLIFERATION; Osteoclasts; Toxicology; Bone; Science & Technology; Life Sciences & Biomedicine; Therapeutic index; DIETARY SILICON; HUMAN ENDOTHELIAL-CELLS
• Research Categories: Health Sciences, Medicine and Surgery; Health Sciences, Toxicology

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 ~50nm 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.