Versatile Functionalization of Polysaccharides via Polymer Grafts: From Design to Biomedical Applications.

Because of their biocompatibility, biodegradability, and unique bioactive properties, polysaccharides have been recognized and directly applied as excellent candidates for various biomedical applications. In order to introduce more functionalities onto polysaccharides, various modification methods were applied to improve the physical-chemical and biochemical properties. Grafting polysaccharides with functional polymers with limited reaction sites maximizes the structural integrity. To the best of our knowledge, great efforts have been made by scientists across the world, including our research group, to explore different strategies for the synthesis and design of controllable polymer-grafted polysaccharides. By the application of some reasonable strategies, a series of polymer-grafted polysaccharides with satisfactory biocharacteristics were obtained. The first strategy involves facile modification of polysaccharides with living radical polymerization (LRP). Functionalized polysaccharides with diverse grafts can be flexibly and effectively achieved. The introduced grafts include cationic components for nuclei acid delivery, PEGylated and zwitterionic moieties for shielding effects, and functional species for bioimaging applications as well as bioresponsive drug release applications. The second synthetic model refers to biodegradable polymer-grafted polysaccharides prepared by ring-opening polymerization (ROP). Inspired by pathways to introduce initiation sites onto polysaccharides, the use of amine-functionalized polysaccharides was explored in-depth to trigger ROP of amino acids. A series of poly(amino acid)-grafted polysaccharides with advanced structures (including linear, star-shaped, and comb-shaped copolymers) were developed to study and optimize the structural effects. In addition, biodegradable polyester-grafted polysaccharides were prepared and utilized for drug delivery. Another emerging strategy was to design polysaccharide-based assemblies with supramolecular structures. A variety of assembly techniques using non-covalent interactions were established to construct different types of polysaccharide-based assemblies with various bioapplications. On the basis of these strategies, polymer-grafted polysaccharides with controllable functions were reported to be well-suited for different kinds of biomedical applications. The exciting results were obtained from both in vitro and in vivo models. Viewing the rapid growth of this field, the present Account will update the concepts, trends, perspectives, and applications of functionalized polysaccharides, guiding and inspiring researchers to explore new polysaccharide-based systems for wider applications.