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.

A Magnetic‐Field Guided Interface Coassembly Approach to Magnetic Mesoporous Silica Nanochains for Osteoclast‐Targeted Inhibition and Heterogeneous Nanocatalysis

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Advances in the application of gold nanoparticles in bone tissue engineering

“…Among them, GNPs and G / HA-NPs have the most significant effect. This ability is also related to the concentration, size and shape of the GNPs [80,81]. Ko et al [82] found that GNPs enhanced bone differentiation of adipose-derived stem cells (ADSCs) at the sizes of 30 nm and 50 nm.…”

Dual delivery of nucleic acids and PEGylated-bisphosphonates via calcium phosphate nanoparticles

“…For free Ale, a dose-dependent cytotoxic effect in monocytic and cancer cell lines was observed for rather high concentrations (20-500 µM, depending on the cell line) [47][48][49][50]. However, adsorption or encapsulation of the BP in nanoparticulate systems were shown to drastically decrease the half maximal inhibitory concentration of Ale, as they facilitated the cellular uptake of the drug [50][51][52][53]. BPs induction of apoptosis is correlated to inhibition of the mevalonate pathway, which leads to reduced biosynthesis of isoprenoid compounds that are essential for protein prenylation [49].…”