Development of a multi-target peptide for potentiating chemotherapy by modulating tumor microenvironment.

Abstract

Finding effective cures against aggressive malignancy remains a major challenge in cancer chemotherapy. Here, we report a "tadpole"-like peptide by covalently conjugating the alanine-alanine-asparagine "tail" residual to the cyclic tumor homing peptide iRGD (CCRGDKGPDC) to afford nRGD, which significantly enhanced tumoricidal effects of doxorubicin, by either co-administered as a physical mixture or as a targeting ligand covalently conjugated to the liposomal carrier. Given twice at an equivalent dose of 5 mg/kg, doxorubicin loaded liposomes modified with nRGD (nRGD-Lipo-Dox) showed excellent antitumor efficacy in 4T1 breast cancer mice, of which 44.4% remained alive for over 90 days without recurrence during the period of investigation. The dramatic improvement in antitumor efficacy was attributed to nRGD-Lipo-Dox which appeared to specifically interact with tumor vascular endothelial cells to achieve efficient tumor penetration, and modulate tumor microenvironment with depletion of tumor associated macrophages.

• Authors: Xu Song, Zhuoya Wan, Tijia Chen, Yao Fu, Kejun Jiang, Xiaoli Yi, Huan Ke, Jianxia Dong, Liuqing Yang, Lin Li, Xun Sun, Tao Gong, Zhirong Zhang
• Journal: Biomaterials (Biomaterials) Vol. 108 Pg. 44-56 (11 2016) ISSN: 1878-5905 [Electronic] Netherlands
• PMID: 27619239 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2016 Elsevier Ltd. All rights reserved.

Chemical References

• Antibiotics, Antineoplastic
• Drug Combinations
• Oligopeptides
• arginyl-glycyl-aspartic acid
• Doxorubicin

Topics

• Animals
• Antibiotics, Antineoplastic (administration & dosage, chemistry)
• Cell Line, Tumor
• Doxorubicin (administration & dosage)
• Drug Combinations
• Drug Synergism
• Female
• Mice
• Mice, Inbred BALB C
• Neoplasms, Experimental (drug therapy, pathology)
• Oligopeptides (administration & dosage, chemical synthesis)
• Protein Engineering (methods)
• Treatment Outcome
• Tumor Microenvironment (drug effects)