Glycopolymer Brushes by Reversible Deactivation Radical Polymerization: Preparation, Applications, and Future Challenges

Abstract

The cellular surface contains specific proteins, also known as lectins, that are carbohydrates receptors involved in different biological events, such as cell–cell adhesion, cell recognition and cell differentiation. The synthesis of well-defined polymers containing carbohydrate units, known as glycopolymers, by reversible deactivation radical polymerization (RDRP) methods allows the development of tailor-made materials with high affinity for lectins because of their multivalent interaction. These polymers are promising candidates for the biomedical field, namely as novel diagnostic disease markers, biosensors, or carriers for tumor-targeted therapy. Although linear glycopolymers are extensively studied for lectin recognition, branched glycopolymeric structures, such as polymer brushes can establish stronger interactions with lectins. This specific glycopolymer topology can be synthesized in a bottlebrush form or grafted to/from surfaces by using RDRP methods, allowing a precise control over molecular weight, grafting density, and brush thickness. Here, the preparation and application of glycopolymer brushes is critically discussed and future research directions on this topic are suggested.

Polymer‐Based Drug‐Free Therapeutics for Anticancer, Anti‐Inflammatory, and Antibacterial Treatment

“…Saccharides play numerous important roles in various diseases including cancer, besides being involved in a variety of biological functions, such as molecular recognition events, cell–cell interactions, cell growth and differentiation, migration, proliferation, adhesion, immune responses, pathogen infections, inflammation, and cancer metastasis. [ 55–64 ] Even though saccharides have attracted considerable attention in the field of biomaterials, they often present weak binding affinities to their respective protein receptors. Nevertheless, stronger affinities can be achieved when lectins present multiple glycosylation binding sites, and saccharide ligands are presented as clusters or aggregates.…”

“…[ 55,60,68–74 ] Therefore, many research groups are attracted to the investigation of polymers as ideal constructs that can mimic natural saccharide ligands and promote higher activities on the basis of an increase in the available binding sites and efficient glycan‐based interactions (see Figure 2 ). [ 55,59–61,69,74,75 ]…”

“…Nevertheless, the present review focuses on synthetic glycopolymers that are defined as synthetic macromolecules with pendant mono and/or oligosaccharide moieties. [ 55,59,61,69,70,74,75,92,93 ] Currently, there are two synthetic approaches for the production of well‐defined synthetic glycopolymers. [ 61,70,74,92,93 ] The first strategy relies on the “direct polymerization” approach of carbohydrate‐substituted monomers, the so‐called glycomonomers, as the sugar source.…”

“…[ 61,70,74,92,93 ] The first strategy relies on the “direct polymerization” approach of carbohydrate‐substituted monomers, the so‐called glycomonomers, as the sugar source. [ 55,59,61,92,93 ] This approach frequently involves complicated procedures for the synthesis of these glycomonomers, as some of them tend to self‐polymerize during the purification procedures. [ 94 ] Therefore, the use of protected monomers is necessary in some cases, which requires an additional step of post‐polymerization deprotection to yield the desired glycopolymer.…”

“…These drawbacks make this method synthetically challenging and time‐consuming. [ 59,61,70,92 ] Additionally, because of the likely loss of the monomers during the polymerization processes, the use of rare and expensive sugar ligands will be the limiting point in this case. [ 95 ] The second strategy relies on the attachment of previously functionalized carbohydrates to polymer carriers or scaffolds bearing reactive functional groups, so‐called “postpolymerization approach,” applying numerous different chemistries, i.e., Huisgen's cycloaddition between azides and alkynes, [ 96 ] coupling thiol−ene [ 97 ] “click” reactions, or amine‐carboxylic acid coupling reactions.…”