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.
Subject(s)
Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Intracellular Space/metabolism , Matrix Metalloproteinase 7/metabolism , Cell Death/drug effects , Cell Line, Tumor , Gels , Humans , HydrolysisABSTRACT
We report a novel peptide-amphiphile having a simple molecular structure that can gelate an aqueous solution at a remarkably low concentration and can be designed to be responsive to a disease-related enzyme by undergoing a drastic morphological change.
Subject(s)
Matrix Metalloproteinase 7/chemistry , Peptides/chemistry , Amino Acid Sequence , Matrix Metalloproteinase 7/metabolism , Micelles , Nanofibers/chemistry , Palmitates/chemistry , Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization , Water/chemistryABSTRACT
Horseradish peroxidase (HRP) is encapsulated in polymerized ionic liquid microparticles (pIL-MP), which are prepared by polymerization of 1-vinyl-3-ethylimidazolium bromide in the presence of the crosslinker N,N'-methylenebis(acrylamide) in a concentrated water-in-oil (W/O) emulsion. pIL-MP encapsulating HRP chemically-modified with comb-shaped polyethylene glycol (PM(13)-HRP) exhibit excellent activity for guaiacol oxidation in an aqueous solution. The PM(13)-HRP in pIL-MP shows more than 2-fold higher activity than that of the enzyme encapsulated in a polyacrylamide microparticle. The catalytic activity declines with an increase in the crosslinker concentration of the pIL-MP, probably due to suppression of substrate diffusion. The activity of PM(13)-HRP in pIL-MP depends on the external environment of the gel (i.e. pH and temperature). The pIL-MP are easily recovered from the reaction mixture by centrifugation, which makes it possible to recycle the biocatalyst for repeated oxidation reactions.
