Anti-tumor Activity Of Hydroxyapatite Nanoparticles

Hydroxyapatite nanoparticles (HAPNs) are a kind of nano materials with high biocompatibility. HAPNs have been reported to exhibit anti-tumor effect on several types of human tumor cells. However, so far, no comprehensive study has been conducted to investigate the toxic effects of HAPNs with different characteristics on different tumor cells.Two kinds of rod-shaped hydroxyapatite nanoparticles, HAPNs and HAPNs-1, with different size and Zeta potential, were synthesized by the aqueous precipitation method. In addition, spherical GS-HAPNs were prepared by the sol-gel method. Our results showed that the smaller rod-shaped HAPNs (20×50nm) with less negative charge (-9.67mV) had stronger anti-tumor activity. HAPNs significantly inhibited cell proliferation and induced apoptosis of MGC80-3, HepG2and HeLa cells, but had no impact on proliferation of normal hepatic cells (L-02) under the same condition. The anti-tumor activity and HAPN-induced apoptosis differed significantly between cell types, and decreased in the order of MGC80-3> HepG2> HeLa. HAPNs increased the activity of caspases-3and-9in tumor cells, but the activation of caspases-8was not observed, indicating that HAPNs induced apoptosis in tumor cells via mitochondrial-dependent pathway. Moreover, HAPNs treatment led to the reactive oxygen species (ROS) generation with a decreased intracellular glutathione (GSH) in the tumor cells, with the most remarkable ROS burst in HeLa cells. HAPNs were found in the cytoplasm of MGC80-3, HepG2, HeLa and L-02cells, but only presented inside the nucleus of tumor cells. More HAPNs seemed to accumulate in the cell nucleus of MGC80-3.In addition to HAPNs, another kind of inorganic nanoparticles, silica nanoparticles with the size of20nm (SNP20), also had cytotoxicity to MGC80-3and HeLa cells. The analyses of the cell nuclear morphology and flow cytometry showed that, SNP20induced apoptosis of MGC80-3and HeLa cells. The cytotoxicity of SNP20was more significant in MGC80-3than in HeLa cells. SNP20were presented inside the cytoplasm, and some particles were even inside the nucleus of tumor cells. SNP20led to the dramatic increase of ROS level in the tumor cells. Therefore, oxidative stress might be the predominant cause of the SNP20-induced apoptosis in tumor cells, which was not the case for HAPNs-induced apoptosis.