Glycopolymers for Drug Delivery: Opportunities and Challenges

Glycopolymers are synthetic polymers with pendant sugars, which hold promise for a range of biomedical applications ranging from tissue engineering to sensing. The known specific interaction of glycopolymers with lectins has inspired researchers to use these polymers to deliver drugs to cells that overexpress lectin receptors. As a result, many glycopolymers─based on mannose, galactose, fructose, or other saccharides–have been used for the targeted delivery of drugs, ranging from traditional anticancer drugs to nucleic acid-derived therapeutics. For drug delivery purposes, glycopolymers are typically processed into nanoparticles that form a matrix to entrap the drug safely, such as micelles, polyplexes, polyion complex micelles, or other nanosized carriers. In vitro and in vivo studies have shown that drugs can indeed be delivered selectively to specific cells by leveraging the selective recognition of surface bound lectins. The key to the interaction between glycopolymers and lectins is the presence of strong intermolecular forces such as hydrogen bonding. The formation of strong hydrogen bonds can, however, also be one of the drawbacks of these materials. Glycopolymers tend to self-aggregate, they interact with drugs in unexpected ways, or they bind proteins in a nonspecific manner. Despite these challenges, nanoparticles based on glycopolymers might offer possibilities that cannot be replicated by other water-soluble polymers. They have already shown that they can effectively deliver drugs in vivo, though more preclinical studies are necessary to enable their broader clinical uptake. Further focus could be directed at an improved understanding of the interface between glycopolymers and the biological surrounding as a key to improve the targeting ability of these nanoparticles in vivo. In this Perspective, I will discuss the aspects to consider when preparing drug delivery carrier using glycopolymers. This will include the interaction of the glyconanoparticles with the drug and the resulting property changes, the types of glycopolymers suitable for drug delivery, the effect of the nanoparticle structure on the affinity to cell surface bound lectins or GLUT transporters and the promising in vivo results that show selective delivery.