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Author Spotlight: Optimization of Ultrashort Peptide Matrices for Colorectal Cancer Organoids
Published on: May 3, 2024
Enzyme-Instructed Self-Assembly of Endoplasmic Reticulum-Targeting Peptides for Selective Modulation of Cancer Cell
Jihun H Roh1, Priyanka Upadhyay1, Chae-Young Lee2
1Department of Chemistry, University of Ulsan, Ulsan 44776, Republic of Korea.
None:
Targeting organelles in cancer cells through enzyme-instructed self-assembly (EISA) enhances cancer cell death more efficiently than intracellular EISA, thereby improving the modulation of cancer cell fate. In this study, we developed a peptide for endoplasmic reticulum (ER) targeting by conjugating p-toluenesulfonamide, an ER-targeting moiety, to one capable of undergoing alkaline phosphatase (ALP)-instructed self-assembly, enabling precise accumulation of peptide assemblies on the ER. In cancer cells with elevated ALP expression, the peptide assemblies selectively accumulated on the ER, unlike in normal cells with low ALP levels, inducing ER stress and leading to ER dysfunction. Consequently, apoptosis and necroptosis were induced selectively in cancer cells. EISA with ER-targeting peptides lowered the IC50 value by more than 2-fold compared to intracellular EISA lacking ER-targeting, effectively overcoming its concentration-dependent challenges.
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