Anti-tumor effects of brucine immuno-nanoparticles on hepatocellular carcinoma

Jian-Min Qin¹, Pei-Hao Yin¹, Qi Li¹, Zhong-Qiu Sa¹, Xia Sheng¹, Lin Yang¹, Tao Huang¹, Min Zhang¹, Ke-Pan Gao², Qing-Hua Chen², Jing-Wei Ma³, He-Bai Shen^3
1Department of General Surgery, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, ²National Pharmaceutical Engineering Research Center; Shanghai Institute of Pharmaceutical Industry, ³Department of Physical Chemistry, Shanghai Normal University, Shanghai, People's Republic of China

Background: Hepatocellular carcinoma is difficult to diagnose early, and most patients are already in the late stages of the disease when they are admitted to hospital. The total 5-year survival rate is less than 5%. Recent studies have showed that brucine has a good anti-tumor effect, but high toxicity, poor water solubility, short half-life, narrow therapeutic window, and a toxic dose that is close to the therapeutic dose, which all limit its clinical application. This study evaluated the effects of brucine immuno-nanoparticles (BIN) on hepatocellular carcinoma.
Materials and methods: Anionic polymerization, chemical modification technology, and phacoemulsification technology were used to prepare a carboxylated polyethylene glycol-polylactic acid copolymer carrier material. Chemical coupling technology was utilized to develop anti-human AFP McAb-polyethylene glycol-polylactic acid copolymer BIN. The size, shape, zeta potential, drug loading, encapsulation efficiency, and release of these immune-nanoparticles were studied in vitro. The targeting, and growth, invasion, and metastasis inhibitory effects of this treatment on liver cancer SMMC-7721 cells were tested.
Results: BIN were of uniform size with an average particle size of 249 ± 77 nm and zeta potential of -18.7 ± 4.19 mV. The encapsulation efficiency was 76.0% ± 2.3% and the drug load was 5.6% ± 0.2%. Complete uptake and even distribution around the liver cancer cell membrane were observed.
Conclusion: BIN had even size distribution, was stable, and had a slow-releasing effect. BIN targeted the cell membrane of the liver cancer cell SMMC-7721 and significantly inhibited the growth, adhesion, invasion, and metastasis of SMMC-7721 cells. As a novel drug carrier system, BIN are a potentially promising targeting treatment for liver cancer.

Keywords: cancer targeting, hepatocellular carcinoma, nanoparticles, targeted drug delivery, anti-tumor effect