All authors read and approved the final manuscript. Acknowledgements This work was supported by the National Science Council, ROC (NSC 98-2320-B-002-010-MY3), the Institute of Biomedical Sciences, Academia Sinica (IBMS-CRC97-P04), and the cooperative research program of NTUCM and CMUCM (99 F008-301).
Hepatocellular carcinoma (HCC) phase 3 is the fifth most common malignant tumor, and there is only one cancer that causes more deaths worldwide. The overall 5-year survival rate is less than 5%. Each year some 564,000 new cases are diagnosed, and 549,000 people die. The poor prognosis is mainly due to common portal vein tumor invasion, which can cause high rates of intrahepatic metastasis and postoperative recurrence. Even in the early stages after radical resection, the metastasis and recurrence rate is 61.

5%.1�C3 Currently, the primary treatment for primary liver cancer is surgery resection. Primary liver cancer is often accompanied by varying degrees of cirrhosis, which is reported in 70%�C90% of all cases. The risk of cirrhosis is enormously increased with respect to liver cirrhosis due to the high sensitivity of the hardened liver to ischemia and blood loss. Long-term hepatic inflow occlusion and massive blood loss can easily lead to postoperative acute liver failure. The overall surgical resection rate is 15%�C20%.4,5 Ziser et al found that patients with cirrhosis undergoing surgeries had a perioperative complication rate of 30.1% and mortality rate of 11.6%.6 Liver transplantation for the treatment of liver cancer can completely resect the tumor and also radically improve the liver function of the patient.

Especially for unresectable liver cancer or patients who cannot undergo liver resection, liver transplantation is the only radical surgical treatment. Nevertheless, tumor recurrence and metastasis significantly restrict the feasibility of liver transplantation. Calne et al reported that 37.5% of patients receiving liver transplants died of tumor recurrence from 2 months to 5 years after the surgery. The 5-year survival rate was 18.6%.7 For patients who cannot tolerate surgery or bear a high risk of recurrence and metastasis after the surgery and transplantation, the alternative treatments include systemic and local chemotherapy. These can control tumor growth to some extent, but some side effects such as poor targeting, low sensitivity, short effecting time, and high toxicity all significantly restrict their clinical application.

8�C10 Therefore, the development of a new drug delivery system characterized by effective targeting of the cancer cells, strong anti-tumor effects, local drug accumulation, GSK-3 slow release, and lower systemic toxicity is the focus for liver cancer treatment and the prevention of recurrence and metastasis. Brucine is a weak basic indole alkaloid.