期刊
ADVANCED HEALTHCARE MATERIALS
卷 10, 期 4, 页码 -出版社
WILEY
DOI: 10.1002/adhm.202000416
关键词
cancer; enzymes; peptides; self-assembly; trypsin
资金
- NIH [CA142746]
This study discovered a readily available peptide that selectively inhibits cancer cells by forming peptide assemblies on the endoplasmic reticulum (ER) through enzyme-instructed self-assembly (EISA), resulting in ER stress and eventual cell death. It offers a promising new strategy for potential cancer therapy by targeting cancer cell subcellular organelles.
Selectively targeting the endoplasmic reticulum (ER) of cancer cells, though promising a new strategy for cancer therapy, remains underdeveloped. Enzyme-instructed self-assembly (EISA) is emerging as a promising approach for selectively targeting ER of cancer cells. This work reports an easily accessible branched peptide that consists of a D-tetrapeptide backbone and a branch with the sequence of KYDKKKKDG (K: lysine; Y: tyrosine; D: aspratic acid; G: glycine), being an EISA substrate of typsin-1 (PRSS1), selectively inhibits cancer cells. Depending on the type of cells, the level of PRSS1 expression dictates the cytotoxicity of the branched peptide. Moreover, immunostaining and fluorescent imaging reveal that PRSS1 overexpresses on the ER of a high-grade serous ovarian cancer cell line (OVSAHO). The overexpression of PRSS1 renders the branched peptide to exhibit high selectivity against OVSAHO by the in situ formation of the peptide assemblies on the ER of OVSAHO cells, which causes ER stress and eventual cell death. This work, illustrating trypsin-guided EISA for inhibiting cancer cells by enzymatic reaction on ER for the first time, offers a new way to target the subcellular organelles of cancer cells for potential cancer therapy.
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