Modular Design of Supramolecular Ionic Peptides with Cell-Selective Membrane Activity

Chembiochem. 2021 Nov 16;22(22):3164-3168. doi: 10.1002/cbic.202100323. Epub 2021 Sep 22.

Abstract

The rational design of materials with cell-selective membrane activity is an effective strategy for the development of targeted molecular imaging and therapy. Here we report a new class of cationic multidomain peptides (MDPs) that can undergo enzyme-mediated molecular transformation followed by supramolecular assembly to form nanofibers in which cationic clusters are presented on a rigid β-sheet backbone. This structural transformation, which is induced by cells overexpressing the specific enzymes, led to a shift in the membrane perturbation potential of the MDPs, and consequently enhanced cell uptake and drug delivery efficacy. We envision the directed self-assembly based on modularly designed MDPs as a highly promising approach to generate dynamic supramolecular nanomaterials with emerging membrane activity for a range of disease targeted molecular imaging and therapy applications.

Keywords: cell selectivity; drug delivery; membrane activity; molecular imaging; self-assembly.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Cell Membrane / chemistry
  • Cell Membrane / metabolism*
  • HeLa Cells
  • Humans
  • Ions / chemical synthesis
  • Ions / chemistry
  • Ions / metabolism
  • Macromolecular Substances / chemical synthesis
  • Macromolecular Substances / chemistry
  • Macromolecular Substances / metabolism
  • Molecular Structure
  • Particle Size
  • Peptides / chemical synthesis
  • Peptides / chemistry
  • Peptides / metabolism*

Substances

  • Ions
  • Macromolecular Substances
  • Peptides