Antitumor effects of polydopamine coated hydroxyapatite nanoparticles and its mechanism: Mitochondria-targeted ROS and calcium channels

Nano hydroxyapatite (nHA) has been acknowledged for its inhibition efficiency on tumor cells and its excellent biocompatibility for normal tissue and cells. However, the low inhibitory efficiency of tumor cells and the ambiguous inhibitory mechanism limited its further application. In this work, four kinds of nHA with different sizes was prepared, and the one with the highest inhibition efficiency on 4T1 cells was screened as a substrate for developing the nanoparticles coated with polydopamine (PDA) coating, which was named nHA-PDA. Both in vivo and in vitro experiments were employed, and the results showed significantly higher inhibitory activity against 4T1 cells and 4T1-bared tumors by nHA-PDA. Further investigation revealed that the oxidative stress induced by PDA results in a large Reactive Oxygen Species (ROS) accumulation, thus triggering the mitochondria-dependent apoptosis pathway ROS-JNK/MAPK and inducing the cascade reaction of inhibiting the anti-apoptosis protein-Bcl-2 expression and activating the expression of the critical genes in apoptosis signaling pathway (caspase 3 and caspase 9). Besides, the significant increase of intracellular [Ca2+] may also be an essential reason for the damage of mitochondria, eventually leading to apoptosis.