| Summary: | The aim of this study was to prepare a biomimetic selenium substituted calcium phosphate system for potential application in osteosarcoma therapy. Calcium phosphate (CaP) systems substituted with selenite ions were prepared by the wet precipitation method, using biogenic CaCO<sub>3</sub> (derived from cuttlefish bone), CO(NH<sub>2</sub>)<sub>2</sub>-H<sub>3</sub>PO<sub>4</sub>, and Na<sub>2</sub>SeO<sub>3</sub>·5H<sub>2</sub>O as reagents. Starting reaction mixtures were prepared based on the formula for selenite-substituted hydroxyapatite, Ca<sub>10</sub>(PO<sub>4</sub>)<sub>6-<i>x</i></sub>(SeO<sub>3</sub>)<i><sub>x</sub></i>(OH)<sub>2</sub>, with Ca/(P + Se) molar ratio of 1.67 and Se/(P + Se) molar ratio of: 0, 0.01, 0.05, and 0.10, respectively. The prepared CaP powders were characterized by Fourier transform infrared spectrometry, elemental analysis, scanning electron microscopy, X-ray powder diffraction analysis and Rietveld refinement studies. Phase transformation and ion release were analyzed during 7 days of incubation in simulated body fluid at 37 °C. The metabolic activity of healthy and osteosarcoma cell lines was assessed by cell cytotoxicity and viability test. The as-prepared powders were composed of calcium-deficient carbonated hydroxyapatite (HAp), octacalcium phosphate (OCP), and amorphous calcium phosphate (ACP). Along with the selenite substitution, the presence of Sr<sup>2+</sup>, Na<sup>+</sup>, and Mg<sup>2+</sup> was detected as a result of using cuttlefish bone as a precursor for Ca<sup>2+</sup> ions. Inductively coupled plasma mass spectrometry analysis showed that the Se/(P + Se) molar ratios of selenite substituted powders are lower than the nominal ratios. Heat treated powders were composed of HAp, <i>α</i>-tricalcium phosphate (<i>α</i>-TCP) and <i>β</i>-tricalcium phosphate (<i>β</i>-TCP). Doping CaP structure with selenite ions improves the thermal stability of HAp. The powder with the Se/(P + Se) molar ratio of 0.007 showed selective toxicity to cancer cells.
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