A tumor-penetrating recombinant protein anti-EGFR-iRGD enhance efficacy of paclitaxel in 3D multicellular spheroids and gastric cancer in vivo

作者：Sha, Huizi; Li, Rutian; Sian, Xinyu; Liu, Qin; Xie, Chen; Xin, Xiaoyan; Kong, Weiwei; Qian, Xiaoping; Jiang, Xiqun; Hu, Wenjing^*; Liu, Baorui

来源：European Journal of Pharmaceutical Sciences, 2015, 77: 60-72.

DOI：10.1016/j.ejps.2015.05.020

• Recombinant protein
• iRGD
• Anti-EGFR single-domain antibody
• Multicellular spheroids
• Gastric cancer
• Paclitaxel

It has been a major challenge for drug penetration in solid tumor tissues because of the complicated tumor microenvironment. We have previously constructed a protein of bispecific targets and high permeability named anti-EGFR-iRGD and investigated its inhibiting cell proliferation of gastric cancer. Paclitaxel (PTX) is widely used for treating various kinds of cancer. In this paper, we investigated the effects of anti-EGFR-iRGD in combination with chemotherapeutic drugs including PTX in epidermal growth factor receptor highly expressing gastric cancer. We demonstrated the therapeutic efficacy of PTX combined with anti-EGFR-iRGD on monolayer cells (2D), multicellular spheroids (3D) and tumor-bearing mice for the first time and investigated the mechanism of this synergy effect. Our results provide impetus for further studies to use anti-EGFR-iRGD with standard cytotoxic treatment regimens for enhancing therapy of gastric cancer patients.

• 出版日期2015-9-18
• 单位南京大学