肽
化学
生物物理学
选择性
细胞穿透肽
癌细胞
赖氨酸
结合
体外
体内
细胞
阿霉素
组合化学
生物化学
癌症
氨基酸
生物
数学分析
数学
生物技术
催化作用
遗传学
化疗
作者
Seung‐Eun Chong,Dong-Hyun Lee,Jin-Seok Oh,Seo Young Kang,Su‐Jung Choi,So Hee Nam,Jaehoon Yu,Heebeom Koo,Yan Lu
出处
期刊:Biomaterials Science
[The Royal Society of Chemistry]
日期:2021-01-01
卷期号:9 (23): 7826-7831
被引量:3
摘要
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, ZHER2:342 (ZHER2), and a dimeric α-helical leucine- and lysine-rich peptide, LK-2. ZHER2 and LK-2 are linearly fused together and expressed in a prokaryotic system to create the LK-2-ZHER2 protein, which can successfully distinguish and penetrate HER2-overexpressing cancer cells at nanomolar concentrations. LK-2-ZHER2 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-ZHER2 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.
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