Glycopolymers against pathogen infection

Abstract

Glycomacromolecules show significant potential as antimicrobials. We highlight recent studies on their performance in hindering host cell entry and biofilm formation, and their potential as drug delivery and diagnostic agents.

Glycan-Presenting Coacervates Derived from Charged Poly(active esters): Preparation, Phase Behavior, and Lectin Capture

“…The non-binding carbohydrate layer leads to steric shielding of charge–charge interactions with the protein and bacteria at the droplet surface, which lowers their uptake. Such steric repulsion effects of glycans are quite common, for example, at the cell glycocalyx and are used for the design of antiviral/antibacterial glycopolymer drugs. , Also, the enrichment of ConA at the periphery of the pure glycan-free polyelectrolyte droplets (Figure , right) suggests such surface effects. Similar protein surface enrichment was found in different complex coacervate/protein systems , and explained by either a net surface charge of the droplets or partitioning of non-charged residues at the interface.…”

“…Carbohydrate-mediated interactions dictate many biological processes on the cellular level, for example, adhesion, communication, signal transduction, or fertilization. , Lectins, an important class of carbohydrate-binding proteins, decorate the surface of pathogens and enable adhesion to the cell’s glycocalyx, which is a critical step in infection processes. − Since the interaction of a single carbohydrate ligand with a protein is rather weak, nature employs multivalency to increase the binding affinity and selectivity. , Multivalent synthetic carbohydrate-presenting scaffolds such as linear glycopolymers, branched scaffolds, or particle-based glycocalyx mimetics via gold nanoparticles, micelles, vesicles, or microgels were developed to acquire insights into the molecular mechanisms of multivalent carbohydrate interactions. − At a high density of carbohydrate units, these scaffolds can achieve a lectin-binding avidity that is an order of magnitude larger in comparison to a single unit. , A potential application of such glycoconjugates is the treatment and prevention of infections by binding and blocking pathogenic lectins and their attachment to the glycocalyx. − Furthermore, responsive glycopolymers allow controlling the avidity by triggering an increase or decrease of the carbohydrate density or accessibility. − Mostly so far, thermoresponsive polymers with uncharged polar repeat units are used to form dense solid phase-separated aggregates upon a temperature change. In addition, some work was done on solid carbohydrate-presenting scaffolds that are held together and self-assemble by electrostatic interactions. , …”

Design of Glycopolymers for Controlling the Interactions with Lectins

“…Viruses have lectins on their surface and are taken up by binding to glycoconjugates on the cell surface. [15] In addition, in the case of bacteria, in addition to the behavior of being taken up into cells, toxin proteins that bind to glycoconjugates of cells may also be produced. This chapter summarizes the design of glycopolymers that bind to lectins related to such pathogens.…”

“…Lectins are involved in the infection of pathogens such as viruses and bacteria. Viruses have lectins on their surface and are taken up by binding to glycoconjugates on the cell surface [15] . In addition, in the case of bacteria, in addition to the behavior of being taken up into cells, toxin proteins that bind to glycoconjugates of cells may also be produced.…”

Structure-Controllable and Mass-Produced Glycopolymersomes as a Template of the Carbohydrate@Ag Nanobiohybrid with Inherent Antibacteria and Biofilm Eradication

“…Glycopolymer-based nanomaterials have emerged as a promising potential platform for the therapeutic applications of pathogen-infected diseases . Lectins are a kind of protein distributed on the surface of cells and perform functions by binding the specific carbohydrates. , The multivalency of glyconanomaterials can be more inclined to adhere to the cell surface of bacteria compared to the molecular glycopolymers through multivalent carbohydrate–protein recognitions (CPRs). , Besides, the formulation of glycopolymers into glyconanostructures with good biocompatibility and low toxicity is capable of encapsulating antibacterial/antibiofilm agents for targeted delivery and enhanced antibacterial activity, as well as improved biofilm dispersal efficacy. − To date, a wide dimension of glyconanostructures with different sizes and shapes, including micelles, cylinders, and polymersomes, have been developed for the disease treatment caused by bacteria and biofilms. , Among these nanostructures, polymersomes have received particular attention for biological applications due to their capability of encapsulating both hydrophobic and hydrophilic guests. Meanwhile, polymersomes were designed to mimic biological liposomes, which showed different functions in the organism, such as intercellular and intracellular transport substances and communications. , However, the polymersomes possess a more stable structure and more accessible functionalization than biological liposomes. − Functionalized polymersomes have been used for the treatment of various diseases caused by bacteria and biofilms with satisfying outcomes. , It remains a huge potential to develop glycopolymersomes to eradicate the pathogens and biofilms, which cause various diseases, such as dental caries.…”