journal article·2022-09-21Open access

Hyaluronan Brush-like Copolymers Promote CD44 Declustering in Breast Cancer Cells

Ana M. Carvalho, Jesus Valcarcel, Diana Soares da Costa, Marisa Gomes, José Antonio Vázquez, Rui L. Reis, Ramon Novoa-Carballal, Iva Pashkuleva

ACS Applied Materials & Interfaces· Volume 14· Issue 37

Abstract

We report on the synthesis of hyaluronan (HA) brush-like copolymers and their application as antagonists of tumorigenic CD44-HA interactions. HA (4.8 kDa, ca. 24 saccharides) was grafted on 2-hydrohyethyl methacrylate (HEMA) by end-on oxime ligation. The obtained copolymers were compared with low and high molecular weight HA in terms of hydrolysis kinetics in the presence of hyaluronidase (isothermal titration calorimetry) and interactions with CD44 (surface plasmon resonance). The results evidenced that the high molecular weight HA and HA-g-HEMA have a much higher affinity to CD44 than low molecular weight HA. Additionally, slower enzymatic degradation was observed for the copolymer, making it an excellent candidate for active targeting of tumorigenic CD44-HA interactions. We, therefore, investigated the effect of the copolymer on cancer cell lines with different expression of CD44 and observed an efficient declustering of CD44 that is usually associated with reduction of metastasis and drug resistance.
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Research context

OpenAlex topics: Proteoglycans and glycosaminoglycans research · Glycosylation and Glycoproteins Research · Protease and Inhibitor Mechanisms

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

3B’s Research Group, I3Bs – Research Institute on Biomaterials, Biodegradables and Biomimetics, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, Avepark, Parque de Ciência e Tecnologia, Zona Industrial da Gandra, 4805-017Barco, Portugal

ICVS/3B’s − PT Government Associate Laboratory, 4710-057Braga/Guimarães, Portugal

Grupo de Reciclado y Valorización de Materiales Residuales (REVAL), Instituto de Investigacións Mariñas (IIM-CSIC), Eduardo Cabello 6, Vigo36208, Galicia, Spain

Funding

Funda??o para a Ci?ncia e a Tecnologia

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