体内
癌症研究
乳腺癌
癌细胞
细胞凋亡
受体
肽
细胞生长
化学
癌症
细胞生物学
程序性细胞死亡
生物
生物化学
遗传学
生物技术
作者
Lu Zhang,Jiang Di,Nian Jiang,Tatu Rojalin,Christopher M. Baehr,Dalin Zhang,Wenwu Xiao,Yi Wu,Zhaoqing Cong,Jian Jian Li,Yuanpei Li,Lei Wang,Kit S. Lam
标识
DOI:10.1038/s41565-019-0626-4
摘要
Human epidermal growth factor receptor 2 (HER2) is overexpressed in >20% of breast cancers. Dimerization of HER2 receptors leads to the activation of downstream signals enabling the proliferation and survival of malignant phenotypes. Owing to the high expression levels of HER2, combination therapies are currently required for the treatment of HER2+ breast cancer. Here, we designed non-toxic transformable peptides that self-assemble into micelles under aqueous conditions but, on binding to HER2 on cancer cells, transform into nanofibrils that disrupt HER2 dimerization and subsequent downstream signalling events leading to apoptosis of cancer cells. The phase transformation of peptides enables specific HER2 targeting, and inhibition of HER2 dimerization blocks the expression of proliferation and survival genes in the nucleus. We demonstrate, in mouse xenofraft models, that these transformable peptides can be used as a monotherapy in the treatment of HER2+ breast cancer. HER2-targeting peptide-based micelles transform into nanofibrils on binding to HER2 on cancer cells, triggering cancer cell apoptosis and tumour death in vivo.
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