Inhibition of metastatic tumor growth and metastasis via targeting metastatic breast cancer by chlorotoxin-modified liposomes.

Abstract

A liposome system modified with chlorotoxin (ClTx), a scorpion venom peptide previously utilized for targeting brain tumors, was established. Its targeting efficiency and antimetastasis behavior against metastatic breast cancer highly expressed MMP-2, the receptor of ClTx, were investigated. 4T1, a metastatic breast cancer cell line derived from a murine breast tumor, was selected as the cell model. As results, the ClTx-modified liposomes displayed specific binding to 4T1 as determined by flow cytometry and confocal imaging. The cytotoxicity assay revealed that the ClTx modification increased the toxicity compared with nonmodified liposomes. In addition, the modified liposomes also exhibited high in vivo targeting efficiency in the BALB/c mice bearing 4T1 tumors. Importantly, this system inhibited the growth of metastatic tumor and prevented the incidence of lung metastasis in mice bearing 4T1 tumors with only low systemic toxicity. The data obtained from the in vitro and in vivo studies confirmed that the ClTx-modified liposomes increased the drug delivery to metastatic breast cancers. This study proved that the ClTx-modified liposomes had targeting ability to metastatic breast cancer in addition to brain cancer, and displayed an obvious antimetastasis effect. Generally, it may provide a promising strategy for metastatic breast cancer therapy.

• Authors: Chao Qin, Bing He, Wenbing Dai, Hua Zhang, Xueqing Wang, Jiancheng Wang, Xuan Zhang, Guangji Wang, Lifang Yin, Qiang Zhang
• Journal: Molecular pharmaceutics (Mol Pharm) Vol. 11 Issue 10 Pg. 3233-41 (Oct 06 2014) ISSN: 1543-8392 [Electronic] United States
• PMID: 24559485 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Liposomes
• Scorpion Venoms
• Chlorotoxin

Topics

• Animals
• Brain Neoplasms (drug therapy, secondary)
• Breast Neoplasms (complications, drug therapy)
• Cell Line, Tumor
• Drug Delivery Systems
• Female
• Liposomes (chemistry)
• Mammary Neoplasms, Experimental (drug therapy)
• Mice
• Mice, Inbred BALB C
• Scorpion Venoms (chemistry, therapeutic use)
• Xenograft Model Antitumor Assays