title: Concentration-dependent effects of alendronate and pamidronate functionalized gold nanoparticles on osteoclast and osteoblast viability.
abstract: Severe osteoporotic diseases, such as Paget's disease, Osteogenesis Imperfecta, and Legg Calve Perthes disease, lack treatments that address the pathobiology of the diseases, as well as, long-term and prospective studies. Bisphosphonates, which are known to dramatically hinder the viability of osteoclast cells, along with gold nanoparticles (GNP) are a potential theranostic for osteoporotic diseases. We evaluated GNP functionalized with two different bisphosphonates, namely, alendronate and pamidronate. RANKL differentiated murine pre-osteoclasts (Raw 264.7) and murine osteoblasts (7F2) were treated with varying concentrations ranging from 0.1-5 µM of free and GNP bound bisphosphonates. GNPs with an average size of ∼15 nm were functionalized with alendronate and pamidronate through surface modification by self-assembly. MTT viability assay results show no changes in viability of the osteoclasts when treated with free bisphosphonates in the range of 1-5 µM, but significant decrease on treatment with functionalized GNP at concentrations above the range of 0.1-1 µM depending on the bisphosphonate. Osteoblast cell viability is maintained at all but the highest concentrations used. Qualitative and quantitative characterization by Western Blot for RANKL expression in the osteoblast cell line shows that expression is largely maintained. These results provide a basis for methods that use bisphosphonate functionalized GNP in the treatment of osteoporotic bone diseases. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 21-29, 2017.
authors.affiliation: Department of Chemical & Biomedical Engineering, University of South Florida, Tampa, Florida.
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Conners
authors.affiliation: Department of Chemical & Biomedical Engineering, University of South Florida, Tampa, Florida.
authors.forename: Venkat R
authors.initials: VR
authors.lastname: Bhethanabotla
authors.affiliation: Department of Chemical & Biomedical Engineering, University of South Florida, Tampa, Florida.
authors.forename: Vinay K
authors.initials: VK
authors.lastname: Gupta
mesh_terms: D019386:Alendronate / Q000493:pharmacokinetics*; D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D004164:Diphosphonates / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006046:Gold / Q000737:chemistry / Q000494:pharmacology; D053768:Metal Nanoparticles / Q000737:chemistry*; D051379:Mice; D010006:Osteoblasts / Q000166:cytology / Q000378:metabolism*; D010010:Osteoclasts / Q000166:cytology / Q000378:metabolism*; D000077268:Pamidronate; D000067996:RAW 264.7 Cells
chemical_list: D004164:Diphosphonates; D006046:Gold; D000077268:Pamidronate; D019386:Alendronate
keywords: bisphosphonate; bone; gold nanoparticles; nanomedicine; osteoporotic disease