International Journal of Pharmaceutics ( IF 5.3 ) Pub Date : 2022-02-22 , DOI: 10.1016/j.ijpharm.2022.121609 Huimin Liu 1 , Dianlong Jia 2 , Fengjiao Yuan 3 , Feifei Wang 2 , Danfeng Wei 4 , Xiaohui Tang 1 , Baoqing Tian 1 , Shuhui Zheng 2 , Ruohan Sun 2 , Jing Shi 1 , Qing Fan 1
Photothermal therapy (PTT), mediated by tumor-targeted drug delivery of indocyanine green (ICG), is a promising strategy for cancer therapy. Human epidermal growth factor receptor 3 (Her3) is highly expressed in several solid tumors and is an ideal target for tumor diagnosis and therapy. This study prepared a Her3-specific dimeric affibody (ZHer3) using an Escherichia coli expression system. The affibody could bind explicitly to Her3-positive MCF7 and LS174T cells, rather than to Her3-negative SKOV-3 cells in vitro. ICG was coupled with the ZHer3 affibody (ICG-ZHer3) through an N-hydroxysuccinimide (NHS) ester reactive group for tumor-targeted delivery. As expected, Her3-positive cells were selectively and efficiently killed by ICG-ZHer3-mediated PTT in vitro. In vivo, ICG-ZHer3 preferentially accumulated in Her3-positive LS174T tumor grafts because of the tumor-targeting ability of the ZHer3 affibody. As a result of the local generation of cytotoxic reactive oxygen species and hyperthermia, the growth rates of LS174T tumor grafts were significantly inhibited by ICG-ZHer3-mediated PTT, and ICG-ZHer3 showed good safety performance during short-term treatment. In conclusion, these results demonstrated that ICG-ZHer3 is a promising photosensitizer for PTT against Her3-positive tumors.
中文翻译:
Her3 特异性 affibody 介导的 ICG 肿瘤靶向递送增强了针对 Her3 阳性肿瘤的光热疗法
由吲哚菁绿 (ICG) 的肿瘤靶向药物递送介导的光热疗法 (PTT) 是一种很有前景的癌症治疗策略。人表皮生长因子受体3(Her3)在几种实体瘤中高度表达,是肿瘤诊断和治疗的理想靶点。本研究使用大肠杆菌表达系统制备了 Her3 特异性二聚体亲和体 (Z Her3 )。affibody 可以显式结合 Her3 阳性 MCF7 和 LS174T 细胞,而不是体外 Her3 阴性 SKOV-3细胞。ICG 与 Z Her3亲和体(ICG-Z Her3) 通过 N-羟基琥珀酰亚胺 (NHS) 酯反应基团进行肿瘤靶向递送。正如预期的那样,Her3 阳性细胞在体外被 ICG-Z Her3介导的 PTT选择性和有效地杀死。在体内,由于 Z Her3亲和体的肿瘤靶向能力,ICG-Z Her3优先在 Her3 阳性 LS174T 肿瘤移植物中积累。由于局部产生细胞毒性活性氧和热疗,ICG-Z Her3介导的PTT显着抑制了LS174T肿瘤移植物的生长速度,ICG-Z Her3在短期治疗中表现出良好的安全性能。总之,这些结果表明 ICG-Z Her3是一种有前途的光敏剂,用于针对 Her3 阳性肿瘤的 PTT。