Enhanced antitumor and anti-metastasis efficacy against aggressive breast cancer with a fibronectin-targeting liposomal doxorubicin.

Abstract

The chemotherapy of aggressive breast tumor is usually accompanied by a poor prognosis because of the metastasis of tumor cells. Thus, it is important to simultaneously enhance antitumor and anti-metastasis efficacy. Fibronectin and its complexes are expressed on the walls of tumor vessels and in tumor stroma. Moreover, the expression of fibronectin in metastatic sites is even higher than that in primary tumors. Herein, we designed a fibronectin-targeting CREKA-modified liposomal doxorubicin (CREKA-Lipo-Dox) for the therapy of metastatic breast tumor. CREKA-Lipo was uniformly formed with high entrapment efficiency. It exhibited longer blood circulation time compared with free Dox, and there was no significant change compared with PEG-Lipo-Dox. Immunofluorescence results revealed that the CREKA-Lipo-Dox could specifically bind to fibronectin in the tumor vessels and tumor stroma. The antitumor and anti-metastasis efficacy of CREKA-loaded liposome was more obvious than that of free Dox or unmodified Dox-Lipo. Taken together, binding fibronectin by CREKA could be an attractive therapeutic strategy for metastatic breast cancer in the future.

• Authors: Kejun Jiang, Xu Song, Liuqing Yang, Lin Li, Zhuoya Wan, Xun Sun, Tao Gong, Qing Lin, Zhirong Zhang
• Journal: Journal of controlled release : official journal of the Controlled Release Society (J Control Release) Vol. 271 Pg. 21-30 (02 10 2018) ISSN: 1873-4995 [Electronic] Netherlands
• PMID: 29277681 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2017 Elsevier B.V. All rights reserved.

Chemical References

• Antibiotics, Antineoplastic
• Fibronectins
• Oligopeptides
• cysteinyl-arginyl-glutamyl-lysyl-alanyl
• liposomal doxorubicin
• Polyethylene Glycols
• Doxorubicin

Topics

• Animals
• Antibiotics, Antineoplastic (administration & dosage, pharmacokinetics)
• Breast Neoplasms (drug therapy, metabolism, pathology)
• Cell Line, Tumor
• Cell Movement (drug effects)
• Doxorubicin (administration & dosage, analogs & derivatives, pharmacokinetics)
• Female
• Fibronectins (metabolism)
• Male
• Mice, Inbred BALB C
• Oligopeptides (administration & dosage, pharmacokinetics)
• Polyethylene Glycols (administration & dosage, pharmacokinetics)
• Rats, Sprague-Dawley