TY - JOUR
T1 - Chemical Antibody Mimics Inhibit Cadherin-Mediated Cell–Cell Adhesion
T2 - A Promising Strategy for Cancer Therapy
AU - Medina Rangel, Paulina X.
AU - Moroni, Elena
AU - Merlier, Franck
AU - Gheber, Levi A.
AU - Vago, Razi
AU - Tse Sum Bui, Bernadette
AU - Haupt, Karsten
N1 - Publisher Copyright:
© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
PY - 2020/2/10
Y1 - 2020/2/10
N2 - 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.
AB - 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.
KW - adherin
KW - cancer therapy
KW - cell adhesion
KW - molecularly imprinted polymer
KW - therapeutic antibodies
UR - http://www.scopus.com/inward/record.url?scp=85076052327&partnerID=8YFLogxK
U2 - 10.1002/anie.201910373
DO - 10.1002/anie.201910373
M3 - Article
C2 - 31659849
AN - SCOPUS:85076052327
SN - 1433-7851
VL - 59
SP - 2816
EP - 2822
JO - Angewandte Chemie - International Edition
JF - Angewandte Chemie - International Edition
IS - 7
ER -
