(9R)-9-Hydroxystearate-Functionalized Hydroxyapatite as Antiproliferative and Cytotoxic Agent toward Osteosarcoma Cells.

Abstract

The possibility to functionalize calcium phosphates with bioactive agents is a promising strategy to design innovative biomaterials for bone repair able to couple the bioactive properties of the inorganic compounds with the therapeutic effect of the functionalizing agent. The R enantiomer of the 9-hydroxystearic acid, (9R)-9-HSA, produced from Dimorphotheca sinuata L. seeds, has proven to act as a natural negative regulator of tumor cell proliferation. On this basis, hydroxyapatite was synthesized with increasing contents of (9R)-9-hydroxystearate, up to ∼8.6 wt %. The incorporation of HSA in the composite nanocrystals induces a reduction of the crystal mean dimensions and of the length of the coherently scattering crystalline domains, which suggest a preferential adsorption onto the hydroxyapatite crystal faces parallel to the c-axis direction. The composite nanocrystals were designed so that their cytostatic and cytotoxic effects toward osteosarcoma cells were modulated by hydroxystearate content. In fact, results of in vitro tests show that the presence of HSA in the composite nanocrystals provokes a significant decrease in SaOS2 osteosarcoma cells proliferation and viability as well as an increase in lactate dehydrogenase, tumor necrosis factor α, and caspase 3 levels, with a cytotoxic effect increasing with HSA content in the nanocrystals.

(9R)-9-Hydroxystearate-Functionalized Anticancer Ceramics Promote Loading of Silver Nanoparticles

“…The values of the mean crystallite sizes along the c -axis (τ 002 ) and along a direction perpendicular to it (τ 310 ), calculated using the Scherrer equation [ 19 ] and reported in Table 1 , display an anisotropic reduction on increasing HSA content. The greater reduction along the direction perpendicular to the c -axis suggests that hydroxystearate is preferentially adsorbed on HA (hk0) faces, as previously reported for anionic polyelectrolytes and acidic amino acids [ 8 , 20 , 21 ].…”

“…Functionalization does not affect significantly the dimensions of the unit cell of the apatitic structure, as shown by the values of the lattice parameters of the different samples reported in Table 1 . The comparison between the XRD patterns reported in Figure 1 a shows that the patterns of the samples functionalized with HSA display slightly broader diffraction reflections than those of HA-Ag50, in agreement with an overall reduction of the length of crystallite sizes (τ hkl ) provoked by HSA functionalization [ 8 ]. The values of the mean crystallite sizes along the c -axis (τ 002 ) and along a direction perpendicular to it (τ 310 ), calculated using the Scherrer equation [ 19 ] and reported in Table 1 , display an anisotropic reduction on increasing HSA content.…”

“…Potassium ( 9R )-9-hydroxystearate was prepared by treatment of ( 9R )-9-hydroxystearic acid, obtained from Dimorphotheca sinuata L. seed oil [ 11 ], with an equimolar amount of KOH in methanol solution, as previously described [ 8 ]. Samples containing HSA were obtained following the above procedure but dissolving potassium ( 9R )-9-hydroxystearate into the (NH 4 ) 2 HPO 4 solution before starting dropping the Ca(NO 3 ) 2 ·4H 2 O solution.…”

“…To this purpose, HA can be functionalized with bioactive ions, molecules, growth factors, and drugs, adding specific characteristics to the osteogenic properties of the calcium phosphate [ 2 , 3 , 4 , 5 , 6 , 7 ]. We have previously synthesized HA at different contents of ( 9R )-9-hydroxystearate (HSA) [ 8 ]. HSA derives from 9-hydroxystearic acid, an endogenous long-chain monohydroxyl fatty acid, which is able to downregulate tumor cell proliferation [ 9 ].…”

Redox signalingvialipid peroxidation regulates retinal progenitor cell differentiation

“…Racemic 9 -HSA was prepared as previously reported (Calonghi et al , 2005), as well as 10-HSA (Ebert et al , 2012). Pure ( R )- 9 -HSA was prepared from Dimorphotheca sinuata seeds according to the procedure previously described (Parolin et al , 2012; Boanini et al , 2016) and its optical purity (>99%) was determined by H NMR analysis after derivatization with ( R )-(-)-O-acetylmandelic acid (Parolin et al , 2012). The synthesized ( R )- 9 -HSA enantiomere, previously shown to be more efficient in inhibiting HDAC1 activity was used for exogenous administration (Parolin et al , 2012).…”