Inhibition of Osteoclast Differentiation and Bone Resorption by Bisphosphonate-conjugated Gold Nanoparticles

Abstract

In recent years, gold nanoparticles (GNPs) have been reported to affect the regeneration of bone tissue. The goal of this study was to improve bone tissue regeneration by using targeted GNPs. We fabricated a functionalized GNPs conjugated with alendronate (ALD), of the bisphosphonate group. Subsequently, the ALD, GNPs, and ALD conjugated GNPs (GNPs-ALD) were analyzed by ultraviolet-visible absorbance (UV-vis) spectrophotometer, Attenuated total reflectance Fourier transform infrared spectrometer (ATR-FTIR), and thermo gravimetric analysis (TGA). The prepared GNPs-ALD were used to investigate their inhibitory effects on the receptor activator of nuclear factor- κb ligand (RANKL)-induced osteoclastogenesis in bone marrow-derived macrophages (BMMs). Additionally, the GNPs-ALD were applied to ovariectomy (OVX)-induced osteoporotic mice and the experiments were evaluated. ALD was found to be successfully conjugated to the GNPs surface, and it displayed significant adhesion onto the bone surface. The in-vitro study indicated that the GNPs, ALD and GNPs-ALD suppressed osteoclast formation in a dose-dependent manner. Furthermore, in the OVX mouse model, the mice treated GNPs-ALD had higher bone density as compared to other OVX mice groups. The results from these tests indicated that GNPs-ALD can be useful agents for preventing and treating osteoporosis.

Development of nanomaterials for bone-targeted drug delivery

“…GNPs show potential for bone-targeted drug delivery because of their ease of functionalization with drugs, targeting moieties, and polymers on gold-thiol bonds [48], as well as their intrinsic ability to upregulate OB activity [49] and downregulate OC differentiation [50,51]. In particular, GNPs can downregulate OC formation by inhibiting the function of the osteoclastogenesis promoter, RANK ligand (RANKL), and by reducing reactive oxygen species (ROS) levels [52].…”

“…Lee et al . sought to functionalize GNPs with Alen to target drugs specifically to bone tissue [51]. The ex vivo results demonstrated the specific binding of GNPs linked to Alen (GNP-Alen), because a large percentage of the GNPs immobilized to the tibia of mice compared with GNPs alone.…”

“…The ex vivo results demonstrated the specific binding of GNPs linked to Alen (GNP-Alen), because a large percentage of the GNPs immobilized to the tibia of mice compared with GNPs alone. They also demonstrated that GNP-Alen had a greater inhibitory effect on OC-related genes ( TRAP, OSCAR, cFos , and NFATc1 ) compared with GNPs or Alen alone [51]. …”

Bone Restoration in Diabetic Osteolysis and Therapeutic Targets

“…Gold nanoparticles (GNPs) have been reported to influence the restoration of bone tissue in recent years. GNPs-ALD (Gold nanoparticles and alendronate) has the highest inhibitory effects towards osteoclast differentiation of bone marrowderived macrophage [59]. Odanacatib, is a cathepsin K inhibitor, offers theoretical advantages over bisphosphonates.…”

Injectable hydrogel composite containing modified gold nanoparticles: implication in bone tissue regeneration

“…For these reasons, GNPs have been widely applied in the fields of drug delivery, diagnosis, and tissue regeneration. [12][13][14][15] In particular, GNPs are suitable for use as functional materials for bone regeneration because of their excellent effects of promoting bone differentiation of stem cells and osteoclast inhibition. 12,[16][17][18][19] In this study, N-acetyl cysteine (NAC) was grafted to GNPs by the surface specificity of GNPs for inducing a synergy effect for promoting bone regeneration.…”