Effect of Hydroxyapatite Nanoparticles on the Growth Potential of Hepatoma Cells in Nude Mice.

Aim: To evaluate the activity of hydroxyapatite (HAP) nanoparticles against the proliferation of hepatoma cells.

Methods: HAP nanoparticles were prepared by homogeneous precipitation. The size distribution and morphology of these nanoparticles were determined by laser particle analysis and transmission electron microscopy, respectively. Xenograft tumor models of human hepatoma cells (Bel-7402) implanted in nude mice under the right scruff skin were established and divided into two groups: treatment and control. Once the xenograft tumor grew to a diameter of 0.8 cm, 0.2 ml HAP nanoparticle suspension was injected into the tumor every day for 2 weeks. The long and short diameters of the tumors were measured before and after HAP injection, and the inhibition rate of tumor growth was calculated. Paraffin tissue sections were prepared from xenograft tumors treated as above for 2 weeks, histologically stained for DNA and agyrophilic nucleolar organizer region (AgNORs), and immuno-histologically stained for proliferating cell nuclear antigens (PCNAs). The stained sections were examined by microscopy. Images of these sections were recorded and analyzed by image analysis system and relevant software for DNA content, AgNOR intensity, and PCNA expression in the nucleus, nucleoli, and hepatoma cells, respectively.

Results: The HAP nanoparticles were uniformly distributed, with a size of 44.6 nm to 86.8 nm. Upon the local injection of the tumor with the HAP nanoparticles, the average volumes of the tumors were significantly reduced compared with those of the control group, which had a tumor inhibition rate of 51.32%. The DNA content, AgNOR intensity, and PCNA expression in the hepatoma cells were all significantly reduced (P < 0.01) compared with those in the control group.

Conclusion: HAP nanoparticles inhibit the proliferation of hepatoma cells in vivo.