Study on the anticarcinogenic effect and acute toxicity of liver-targeting mitoxantrone nanoparticles

摘要

AIM: To study the anticarcinogenic effect and acute toxicity of liver targeting mitoxantrone-nanospheres.METHODS: The anticarcinogenic effect of mitoxantrone-polybutyl cyanoacrylate-nanoparticles ( DHAQ-PBCA-NP ) was investigated by using heterotopic and orthotopic transplantation models of human hepatocellular carcinoma ( HCC ) in nude mice and was compared with mitoxantrone (DHAQ) and doxorubicin (ADR). The acute toxicity of DHAQ-PBCA-NP lyophilized injection in mice was also studied.RESULTS: The tumor inhibition rates of ADR, DHAQ, DHAQ-PBCA-NP to orthotopically transplanted HCC were 60.07%, 67.49% and 99.44%, respectively, but regard to heterotopically transplanted HCC, these were 80.03%, 86.18% and 92.90%, which were concordant with the results acquired by mitosis counting and proliferating cell nuclear antigen (PCNA). After iv administration to mice with DHAQ-PBCA-NP, the LD50 was 16.9 mg/kg ± 3.9 mg/kg, no obvious local irritation was observed and there was no significant damage to the structure of liver cells, and that of the heart, spleen and kidneys.CONCLUSION: The effect of DHAQ-PBCA-NP was significantly higher than that of DHAQ and ADR in the anti-orthotopically transplanted HCC and the acute toxicity was relatively low.