Cancer cell death induced by the intracellular self-assembly of an enzyme-responsive supramolecular gelator

Akiko Tanaka, Yuki Fukuoka, Yuka Morimoto, Takafumi Honjo, Daisuke Koda, Masahiro Goto, Tatsuo Maruyama

    Research output: Contribution to journalArticlepeer-review

    244 Citations (Scopus)

    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.

    Original languageEnglish
    Pages (from-to)770-775
    Number of pages6
    JournalJournal of the American Chemical Society
    Volume137
    Issue number2
    DOIs
    Publication statusPublished - Jan 21 2015

    All Science Journal Classification (ASJC) codes

    • Catalysis
    • Chemistry(all)
    • Biochemistry
    • Colloid and Surface Chemistry

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