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

Abstract

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 antihuman 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

Acknowledgments

The authors thank Professor Yan Zhang for the correction and translation of the manuscript. The authors gratefully acknowledge the financial support from the National Natural Science Foundation of China (No 30873341), the Shanghai Education Commission (No 07CZ017), and the Shanghai Science and Technology Commission (No 1052nm060000).

Disclosure

The authors report no conflicts of interest in this work.