A dimeric α-helical cell penetrating peptide mounted with an HER2-selective affibody,Biomaterials Science

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A dimeric α-helical cell penetrating peptide mounted with an HER2-selective affibody
Biomaterials Science ( IF 5.8 ) Pub Date : 2021-08-12 , DOI: 10.1039/d1bm00819f
Seung-Eun Chong ₁ , Donghyun Lee ₂ , Jae Hoon Oh ₃ , Sunyoung Kang ₁ , Sejong Choi ₁ , So Hee Nam ₁ , Jaehoon Yu ₄ , Heebeom Koo ₂ , Yan Lee ₁

Affiliation

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_HER2:342 (Z_HER2), and a dimeric α-helical leucine- and lysine-rich peptide, LK-2. Z_HER2 and LK-2 are linearly fused together and expressed in a prokaryotic system to create the LK-2-Z_HER2 protein, which can successfully distinguish and penetrate HER2-overexpressing cancer cells at nanomolar concentrations. LK-2-Z_HER2 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 vitro, in 3D spheroids, and in in vivo models. LK-2-Z_HER2 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.

中文翻译：

带有 HER2 选择性 affibody 的二聚体 α-螺旋细胞穿透肽

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，并结合了 HER2 选择性亲和体 Z _HER2:342 (Z _HER2 ) 和富含 α-螺旋富含亮氨酸和赖氨酸的二聚体肽，LK-2。Z _HER2和 LK-2 线性融合在一起并在原核系统中表达以产生 LK-2-Z _HER2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 _HER2能够以偶联物形式在细胞内递送阿霉素，以增强其对 HER2 过表达乳腺癌细胞的抗癌作用，具有很高的选择性。选择性渗透性得到证实体外、3D 球体和体内模型。LK-2-Z _HER2通过结合强大的 CPP 和 affibody 序列，能够克服当前 CPP 的弱点，例如低浓度渗透性差和缺乏选择性。

更新日期：2021-08-26

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