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Chemical Antibody Mimics Inhibit Cadherin‐Mediated Cell–Cell Adhesion: A Promising Strategy for Cancer Therapy
Author(s) -
Medina Rangel Paulina X.,
Moroni Elena,
Merlier Franck,
Gheber Levi A.,
Vago Razi,
Tse Sum Bui Bernadette,
Haupt Karsten
Publication year - 2020
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.201910373
Subject(s) - hela , cell adhesion , cadherin , adhesion , cell , cancer cell , chemistry , cancer research , antibody , cancer , biochemistry , biology , immunology , genetics , organic chemistry
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.