Chemical Antibody Mimics Inhibit Cadherin-Mediated Cell-Cell Adhesion: A Promising Strategy for Cancer Therapy

Angew Chem Int Ed Engl. 2020 Feb 10;59(7):2816-2822. doi: 10.1002/anie.201910373. Epub 2019 Nov 27.

Abstract

One of the most promising strategies to treat cancer is the use of therapeutic antibodies that disrupt cell-cell adhesion mediated by dysregulated cadherins. The principal site where cell-cell adhesion occurs encompasses Trp2 found at the N-terminal region of the protein. Herein, we employed the naturally exposed highly conserved peptide Asp1-Trp2-Val3-Ile4-Pro5-Pro6-Ile7, as epitope to prepare molecularly imprinted polymer nanoparticles (MIP-NPs) to recognize cadherins. Since MIP-NPs target the site responsible for adhesion, they were more potent than commercially available therapeutic antibodies for inhibiting cell-cell adhesion in cell aggregation assays, and for completely disrupting three-dimensional tumor spheroids as well as inhibiting invasion of HeLa cells. These biocompatible supramolecular anti-adhesives may potentially be used as immunotherapeutic or sensitizing agents to enhance antitumor effects of chemotherapy.

Keywords: adherin; cancer therapy; cell adhesion; molecularly imprinted polymer; therapeutic antibodies.

MeSH terms

  • Antibodies / chemistry
  • Antibodies / immunology*
  • Breast Neoplasms / immunology*
  • Breast Neoplasms / pathology
  • Breast Neoplasms / therapy
  • Cadherins / antagonists & inhibitors
  • Cadherins / chemistry
  • Cadherins / immunology*
  • Cell Adhesion / drug effects
  • Cell Adhesion / immunology*
  • Cell Line
  • Female
  • HeLa Cells
  • Humans
  • MCF-7 Cells
  • Molecular Imprinting
  • Nanoparticles / chemistry
  • Optical Imaging
  • Polymers / chemistry
  • Polymers / pharmacology
  • Uterine Cervical Neoplasms / immunology*
  • Uterine Cervical Neoplasms / pathology
  • Uterine Cervical Neoplasms / therapy

Substances

  • Antibodies
  • Cadherins
  • Polymers