材料科学
癌细胞
体内
黑色素瘤
癌症研究
细胞毒性
溶血
药品
体外
癌症
药理学
化学
生物
生物化学
免疫学
遗传学
生物技术
作者
Wei Shen,Yu Zhang,Pengqi Wan,Lin An,Peng Zhang,Chunsheng Xiao,Xuesi Chen
标识
DOI:10.1002/adma.202001108
摘要
Abstract An antineoplastic drug‐free anticancer strategy enabled by host defense peptides (HDPs)‐mimicking synthetic polypeptides is reported. The polypeptide exhibits a broad spectrum of anticancer activity in 12 cancer cell lines, including drug‐resistant and highly metastatic tumor cells. Detailed mechanistic studies reveal that the cationic anticancer polypeptide (ACPP) can directly induce rapid necrosis of cancer cells within minutes through a membrane‐lytic mechanism. Moreover, a pH‐sensitive zwitterionic derivative of ACPP (DA‐ACPP) is prepared for in vivo application. DA‐ACPP shows negligible hemolysis under neutral physiological conditions, and can be converted back to ACPP in slightly acidic tumor environments, resulting in selective killing of cancer cells. Consequently, DA‐ACPP shows an effective inhibition of tumor growth in both 4T1 orthotopic breast tumor models and B16‐F10 melanoma pulmonary metastatic models. Overall, these findings demonstrate that synthetic HDPs‐mimicking polypeptides represent safe and effective antineoplastic agents, which sheds new light on the development of drug‐free synthetic polymers for cancer therapy.
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