Antitumor Effect by Hydroxyapatite Nanospheres: Activation of Mitochondria-Dependent Apoptosis and Negative Regulation of Phosphatidylinositol-3-Kinase/Protein Kinase B Pathway

Hydroxyapatite nanoparticles (HA NPs) have been acknowledged for their benign biocompatibility and proliferation inhibition effect on tumor cells, attracting considerable attention for tumor therapeutics without late effects. However, unnoticeable tumor cytotoxicity of HA NPs limited the final clinical therapeutic efficacy. Herein, a two-phase synthetic approach was developed to synthesize sphere-like HA NPs by varying the conventional growth habit of HA precipitate. We present our in vitro and in vivo experimental evidence that spherical HA NPs have surprisingly high inhibitory activities against tumor cells. We demonstrate further, based on our experimental data, that the underlying cause for the death of the tumor cells is related to two concurrent pathways, the mitochondria-dependent apoptosis pathway and negative regulation of the phosphatidylinositol-3-kinase/protein kinase B (PIK3/AKT) pathway. The present study indicated that HA nanospheres can be engineered as nontoxic specific inhibitors for efficient tumor therapeutics with nanobiomaterials.