This study aimed to improve the biocompatibility and osteogenic property of hydroxyapatite (HAP). So HAP nanoparticles were doped with zinc (Zn), and their surface was modified with a purine nucleotide, guanosine 50-triphosphate (GTP). GTP-loaded nanoparticles (GTP@ZnHAP) were characterised by field emission scanning electron microscopy, Fourier transform infrared, thermogravimetric analysis, zeta potential and ultraviolet–visible spectroscopy. Biological experiments revealed that GTP@ZnHAP nanoparticles were internalised by the cells, inhibiting tumour cell (osteoblast-like cells, Saos-2) expansion with an efficiency more than that observed for ZnHAP nanoparticles and GTP alone. Furthermore, Saos-2 cells were committed to differentiate into the normal osteoblast cells under the influence of GTP@ZnHAP nanoparticles demonstrated by the quantitative assessment of bone-related protein expression (Runx2 and osteocalcin) and cell morphological changes. Moreover, high-performance liquid chromatography analyses disclosed a significant enhancement of intracellular GTP content in GTP@ZnHAP-treated cells, proposing perturbation of intracellular nucleotide equilibrium during the process of osteogenesis induced by GTP@ZnHAP nanoparticles. Overall, GTP@ZnHAP exhibits a better synergistic effect on the modulation of cell growth and induction of osteogenic differentiation in osteosarcoma cells than ZnHAP nanoparticles and GTP alone do. Therefore, GTP@ZnHAP may be regarded as a promising biomaterial for the treatment of bone-related diseases.

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