Molecularly imprinted polymer nanogels targeting the HAV motif in cadherins inhibit cell–cell adhesion and migration. Issue 35 (18th May 2022)

• Record Type: Journal Article
• Authors: Medina Rangel, Paulina X.; Mier, Alejandra; Moroni, Elena; Merlier, Franck; Gheber, Levi A.; Vago, Razi; Maffucci, Irene; Tse Sum Bui, Bernadette; Haupt, Karsten
• Is Part Of: Journal of materials chemistry. Volume 10:Issue 35(2022)
• Page Start: 6688
• Page End: 6697
• Publication Date: 2022-05-18
• Subjects: Materials -- Periodicals; Chemistry, Analytic -- Periodicals; Biomedical materials -- Research -- Periodicals; 543.0284
• DOI: 10.1039/d2tb00680d
• Languages: English
• ISSNs: 2050-750X

Abstract

Abstract : Molecularly imprinted polymer nanogels (MIPs) as synthetic antibody mimics against the HAVDI epitope of N-cadherin specifically inhibit cell–cell aggregation and tumor cell invasiveness by blocking cadherin-mediated interactions. Abstract : Cadherins are cell–surface proteins that mediate cell–cell adhesion. By regulating their grip formation and strength, cadherins play a pivotal role during normal tissue morphogenesis and homeostasis of multicellular organisms. However, their dysfunction is associated with cell migration and proliferation, cancer progression and metastasis. The conserved amino acid sequence His-Ala-Val (HAV) in the extracellular domain of cadherins is implicated in cadherin-mediated adhesion and migration. Antagonists of cadherin adhesion such as monoclonal antibodies and small molecule inhibitors based on HAV peptides, are of high therapeutic value in cancer treatment. However, antibodies are not stable outside their natural environment and are expensive to produce, while peptides have certain limitations as a drug as they are prone to proteolysis. Herein, we propose as alternative, a synthetic antibody based on molecularly imprinted polymer nanogels (MIP-NGs) to target the HAV domain. The MIP-NGs are biocompatible, have high affinity for N-cadherin and inhibit cell adhesion and migration of human cervical adenocarcinoma (HeLa) cells, as demonstrated by cell aggregation and Matrigel invasion assays, respectively. The emergence of MIPs as therapeutics for fighting cancer is still in its infancy and this novel demonstration reinforces the fact that they have a rightful place in cancer treatment.