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Concentration-dependent effects of alendronate and pamidronate functionalized gold nanoparticles on osteoclast and
Christopher M Conners1, Venkat R Bhethanabotla1, Vinay K Gupta1
1Department of Chemical & Biomedical Engineering, University of South Florida, Tampa, Florida.
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.
Insights
Gold nanoparticles (GNP) functionalized with bisphosphonates show promise for treating osteoporotic diseases by selectively reducing osteoclast viability while preserving osteoblasts. This targeted approach offers a new theranostic strategy for bone diseases.
Area of Science:
- Biomaterials Science
- Nanotechnology
- Orthopedics
Background:
- Severe osteoporotic diseases lack targeted therapies addressing disease pathobiology.
- Bisphosphonates inhibit osteoclast viability but require novel delivery systems.
- Gold nanoparticles (GNP) offer potential as theranostic agents for bone diseases.
Purpose of the Study:
- To evaluate gold nanoparticles (GNP) functionalized with alendronate and pamidronate as a potential theranostic for osteoporotic diseases.
- To assess the effect of GNP-bound bisphosphonates on osteoclast and osteoblast cell viability.
- To investigate the impact on Receptor Activator of Nuclear Factor kappa-B Ligand (RANKL) expression in osteoblasts.
Main Methods:
- Functionalization of ~15 nm GNPs with alendronate and pamidronate via surface self-assembly.
- Treatment of RANKL-differentiated murine pre-osteoclasts (Raw 264.7) and murine osteoblasts (7F2) with varying concentrations (0.1-5 µM) of free and GNP-bound bisphosphonates.
- Assessment of cell viability using MTT assay and RANKL expression via Western Blot.
Main Results:
- Free bisphosphonates showed no effect on osteoclast viability at 1-5 µM.
- GNP-bound bisphosphonates significantly decreased osteoclast viability at concentrations above 0.1-1 µM.
- Osteoblast viability was maintained except at the highest concentrations, and RANKL expression remained largely unchanged.
Conclusions:
- Bisphosphonate-functionalized GNPs demonstrate selective toxicity towards osteoclasts, sparing osteoblasts.
- This targeted delivery system presents a promising theranostic approach for managing osteoporotic bone diseases.
- Further research can build upon these findings for developing effective treatments for conditions like Paget's disease.
