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

Paulina X. Medina Rangel, Elena Moroni, Franck Merlier, Levi A. Gheber, Razi Vago, Bernadette Tse Sum Bui, Karsten Haupt

Research output: Contribution to journalArticlepeer-review

42 Scopus citations

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.

Original languageEnglish
Pages (from-to)2816-2822
Number of pages7
JournalAngewandte Chemie - International Edition
Volume59
Issue number7
DOIs
StatePublished - 10 Feb 2020

Keywords

  • adherin
  • cancer therapy
  • cell adhesion
  • molecularly imprinted polymer
  • therapeutic antibodies

ASJC Scopus subject areas

  • Catalysis
  • Chemistry (all)

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