Theranostic Protein Targeting ErbB2 for Bioluminescence Imaging and Therapy for Cancer

A combination of molecular-targeted cancer imaging and therapy is an emerging strategy to improve cancer diagnosis and minimize the side effects of conventional treatments. Here, we generated a recombinant protein, EC1-GLuc-p53C, by fusing EC1 peptide, an artificial ligand of ErbB2, with Gaussia luciferase (GLuc) and a p53-activating peptide, p53C. EC1-GLuc-p53C was expressed and purified from E. coli BL21. In vitro experiments showed that EC1-GLuc-p53c was stable in luminescent activity and selectively targeted ErbB2-overexpressing BT474 cells for bioluminescence imaging. Moreover, the internalized EC1-GLuc-p53C in BT474 cells exerted its function to reactivate p53 and significantly inhibited cellular proliferation. In tumor-bearing mice, the ErbB2-targeted bioluminescence imaging and therapeutic effect of EC1-GLuc-p53C were also observed specifically in BT474 tumors but not in MCF7 tumors, which does not overexpress ErbB2. Thus, the present study demonstrates EC1-GLuc-p53C to be an effective theranostic reagent targeting ErbB2 for bioluminescence imaging and cancer therapy.分子靶向肿瘤成像与治疗联合策略是提升癌症诊断效能、减轻传统治疗不良反应的新兴研究方向。本研究通过将人类表皮生长因子受体2（ErbB2）的人工配体EC1肽（EC1 peptide）、高斯荧光素酶（Gaussia luciferase，GLuc）与p53激活肽p53C融合，制备得到重组蛋白EC1-GLuc-p53C。该重组蛋白可在大肠杆菌BL21（E. coli BL21）中表达并纯化。体外实验结果显示，EC1-GLuc-p53C的发光活性稳定，且可特异性靶向过表达ErbB2的BT474细胞用于生物发光成像。此外，被BT474细胞内吞的EC1-GLuc-p53C可发挥重激活p53的功能，并显著抑制细胞增殖。在荷瘤小鼠模型中，EC1-GLuc-p53C的ErbB2靶向生物发光成像与治疗效应仅在BT474肿瘤中被检测到，而在不表达ErbB2的MCF7肿瘤中未观察到此现象。综上，本研究证实EC1-GLuc-p53C是一种可靶向ErbB2的有效诊疗一体化试剂，可用于生物发光成像与癌症治疗。