Chemotherapy is the most reliable treatment for osteoporosis and osseous metastases. To facilitate better drug delivery for bone treatments, a novel preparation of polymeric nanoparticles with high affinity to bone has been prepared. Two-step synthesis of cholesteryl-functionalized poly(ethylene sodium phosphate) (Ch-PEPn(center dot)Na) was performed via ring-opening polymerization of cyclic phosphoesters and the demethylation. The molecular weight of Ch-PEPn center dot Na could be well controlled by changing the ratio of cholesterol and cyclic phosphoesters. Because Ch-PEPn center dot Na exhibits an amphiphilic nature in aqueous media, Ch-PEP..Na-bearing nanoparticles (PEP.Na NPs) were prepared by a solvent evaporation technique. The size of the nanoparticles investigated in the current study is approximately 100 nm, which was determined by dynamic light scattering (DLS) and transmission electron microscopy (TEM). Due to the presence of highly water-soluble polymer chains, dispersion of PEPn center dot Na NPs in aqueous media was stable for at least I week. Hemolytic activity of PEPn center dot Na NPs was found to be low and PEPirNa NPs did not disintegrate mammalian cell membranes. Additionally, cytotoxicity of PEPn center dot Na NPs was not observed at concentrations below 100 p.,g/mL. The adsorption of PEPn"Na NPs on hydroxyapatite (HAp) microparticles was studied in comparison with poly(ethylene glycol) nanoparticles (PEG NPs). Both PEPn center dot Na NPs and PEG NPs adsorbed well onto HAp microparticles in distilled water with binding equilibrium constants (ICHAp) for PEPn center dot Na NPs and PEG NPs of 3.6 x 10(6) and 7.9 x 10(6), respectively. In contrast, only PEPn center dot Na NPs adsorbed onto HAp microparticles in a saline phosphate buffer. Moreover, the adsorption of PEPn center dot Na NPs onto HAp microparticles occurred even in the presence of 1.2 mM calcium ions or low-pH media. The affinity of the nanoparticles to bovine bone slices was also studied, with the result that large quantities of adsorbed PEPn center dot Na NPs were observed on the slices by scanning electron microscope. (C) 2017 Elsevier B.V. All rights reserved.