Department of Chemistry, Seoul National University, Seoul, 08826, Republic of Korea.
Department of Medical Life Sciences and Department of Biomedicine & Health Sciences, The Catholic University of Korea, Seoul, 06591, Republic of Korea.
Biomater Sci. 2021 Nov 23;9(23):7826-7831. doi: 10.1039/d1bm00819f.
We have developed a cell penetrating peptide (CPP) system with high selectivity and penetrability at nanomolar concentrations with a combination of an HER2-selective affibody, Z (Z), and a dimeric α-helical leucine- and lysine-rich peptide, LK-2. Z and LK-2 are linearly fused together and expressed in a prokaryotic system to create the LK-2-Z protein, which can successfully distinguish and penetrate HER2-overexpressing cancer cells at nanomolar concentrations. LK-2-Z has the ability to intracellularly deliver doxorubicin as a conjugate form to enhance its anti-cancer effect on HER2-overexpressing breast cancer cells with a great selectivity. The selective penetrability was confirmed , in 3D spheroids, and in models. LK-2-Z has the capability to overcome the weak points of current CPPs, such as poor penetrability at low concentrations and a lack of selectivity, by combining powerful CPP and affibody sequences.
我们开发了一种细胞穿透肽 (CPP) 系统，该系统在纳摩尔浓度下具有高选择性和穿透性，结合了一种 HER2 选择性亲和体 Z (Z) 和一种二聚体 α-螺旋亮氨酸和赖氨酸丰富肽 LK-2。Z 和 LK-2 线性融合在一起，并在原核系统中表达，以创建 LK-2-Z 蛋白，该蛋白可以在纳摩尔浓度下成功区分和穿透过表达 HER2 的癌细胞。LK-2-Z 能够将阿霉素作为缀合物形式递送到细胞内，以增强其对过表达 HER2 的乳腺癌细胞的抗癌作用，具有很高的选择性。这种选择性穿透性在 3D 球体和模型中得到了证实。LK-2-Z 具有克服当前 CPP 弱点的能力，例如在低浓度下穿透性差和缺乏选择性，它通过结合强大的 CPP 和亲和体序列来实现这一点。
