期刊
TOXICOLOGY IN VITRO
卷 28, 期 3, 页码 354-364出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.tiv.2013.12.001
关键词
Silica nanoparticles; Toxicity; Therapeutic index; Osteoblasts; Osteoclasts; Bone
类别
资金
- NIAMS [AR056090, AR059364, AR053607]
- Georgia Research Alliance [GRA.VL12.C2]
- Department of Biomedical Engineering at Georgia Institute of Technology, Emory University
- Children's Healthcare of Atlanta, Center for Pediatric Nanomedicine, Atlanta, GA, USA [RC159-G3]
- Biomedical Laboratory Research & Development Service of the VA Office of Research and Development [I01BX002363, 5I01BX000105]
- NIH-NCI [CA136716]
- NIA [AG040013]
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 Stober 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. (C) 2013 Elsevier Ltd. All rights reserved.
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