title: Cancer cell death induced by the intracellular self-assembly of an enzyme-responsive supramolecular gelator.
abstract: We report cancer cell death initiated by the intracellular molecular self-assembly of a peptide lipid, which was derived from a gelator precursor. The gelator precursor was designed to form nanofibers via molecular self-assembly, after cleavage by a cancer-related enzyme (matrix metalloproteinase-7, MMP-7), leading to hydrogelation. The gelator precursor exhibited remarkable cytotoxicity to five different cancer cell lines, while the precursor exhibited low cytotoxicity to normal cells. Cancer cells secrete excessive amounts of MMP-7, which converted the precursor into a supramolecular gelator prior to its uptake by the cells. Once inside the cells, the supramolecular gelator formed a gel via molecular self-assembly, exerting vital stress on the cancer cells. The present study thus describes a new drug where molecular self-assembly acts as the mechanism of cytotoxicity.
authors.affiliation: Department of Chemical Science and Engineering, Graduate School of Engineering, Kobe University , 1-1 Rokkodai, Nada-ku, Kobe 657-8501, Japan.
authors.forename: Akiko
authors.initials: A
authors.lastname: Tanaka
authors.forename: Yuki
authors.initials: Y
authors.lastname: Fukuoka
authors.forename: Yuka
authors.initials: Y
authors.lastname: Morimoto
authors.forename: Takafumi
authors.initials: T
authors.lastname: Honjo
authors.forename: Daisuke
authors.initials: D
authors.lastname: Koda
authors.forename: Masahiro
authors.initials: M
authors.lastname: Goto
authors.forename: Tatsuo
authors.initials: T
authors.lastname: Maruyama
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology*; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D005782:Gels; D006801:Humans; D006868:Hydrolysis; D042541:Intracellular Space / Q000378:metabolism*; D020783:Matrix Metalloproteinase 7 / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; D005782:Gels; D020783:Matrix Metalloproteinase 7