In Vivo Anti-Tumor Activity of Polypeptide HM-3 Modified by Different Polyethylene Glycols (PEG)

International Journal of Molecular Sciences

Zhendong Liu¹  Yinling Ren¹  Li Pan¹ 

[1] Department of Marine Pharmacy, College of Life Science and Technology, China Pharmaceutical University, Nanjing 210009, China;

关键词: PEG modification;    peptides;    HM-3;    anti-tumor;    activities;   

DOI  :  10.3390/ijms12042650

来源: mdpi

【 摘 要 】

HM-3, designed by our laboratory, is a polypeptide composed of 18 amino acids. Pharmacodynamic studies in vivo and in vitro indicated that HM-3 could inhibit endothelial cell migration and angiogenesis, thereby inhibiting tumor growth. However, the half-life of HM-3 is short. In this study, we modified HM-3 with different polyethylene glycols (PEG) in order to reduce the plasma clearance rate, extend the half-life in the body, maintain a high concentration of HM-3 in the blood and increase the therapeutic efficiency. HM-3 was modified with four different types of PEG with different molecular weights (ALD-mPEG_5k, ALD-mPEG_10k, SC-mPEG_10k and SC-mPEG_20k), resulting in four modified products (ALD-mPEG_5k-HM-3, ALD-mPEG_10k-HM-3, SC-mPEG_10k-HM-3 and SC-mPEG_20k-HM-3, respectively). Anti-tumor activity of these four modified HM-3 was determined in BALB/c mice with Taxol as a positive control and normal saline as a negative control. Tumor weight inhibition rates of mice treated with Taxol, HM-3, ALD-mPEG_5k-HM-3, ALD-mPEG_10k-HM-3, SC-mPEG_10k-HM-3 and SC-mPEG_20k-HM-3 were 44.50%, 43.92%, 37.95%, 31.64%, 20.27% and 50.23%, respectively. Tumor inhibition rates in the Taxol, HM-3 and SC-mPEG_20k-HM-3 groups were significantly higher than that in the negative control group. The efficiency of tumor inhibition in the SC-mPEG_20k-HM-3 group (drug treatment frequency: once per two days) was better than that in the HM-3 group (drug treatment frequency: twice per day). In addition, tumor inhibition rate in the SC-mPEG_20k-HM-3 group was higher than that in the taxol group. We conclude that SC-mPEG_20k-HM-3 had a low plasma clearance rate and long half-life, resulting in high anti-tumor therapeutic efficacy in vivo. Therefore, SC-mPEG_20k-HM-3 could be potentially developed as new anti-tumor drugs.

【 授权许可】

CC BY   
© 2011 by the authors; licensee MDPI, Basel, Switzerland.