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

作者：Song, Xu; Wan, Zhuoya; Chen, Tijia; Fu, Yao; Jiang, Kejun; Yi, Xiaoli; Ke, Huan; Dong, Jianxia; Yang, Liuqing; Li, Lin; Sun, Xun; Gong, Tao^*; Zhang, Zhirong^*

来源：Biomaterials, 2016, 108: 44-56.

DOI：10.1016/j.biomaterials.2016.09.001

• nRGD
• iRGD
• Legumain
• Tumor associated macrophage
• Tumor microenvironment

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.

• 出版日期2016-11
• 单位四川大学