Metal ion coordination-crosslinked polysaccharides: Emerging platforms for advanced drug delivery.

Abstract

Natural polysaccharides are attractive drug delivery materials owing to their biocompatibility, biodegradability, and structural tunability. However, conventional polysaccharide-based systems often exhibit limited structural and mechanical stability, insufficient drug-loading capacity, and inadequate regulation of drug release. Metal-ion coordination-mediated crosslinking of polysaccharides endows polysaccharide-based delivery systems with desirable properties such as self-assembly, adhesion, and mechanical tunability, thereby improving drug-loading efficiency, structural stability, and controlled drug release. Moreover, the physicochemical properties and intrinsic biological activities of metal ions may further confer polysaccharide-based systems with additional functions, including antibacterial, antioxidant, catalytic, photothermal, and osteogenic functions. This review summarizes the molecular coordination mechanisms, coordination properties and biological roles of representative metal ions, metal-ion coordination-enabled polysaccharide delivery platforms and their fabrication strategies, as well as coordination-driven improvements in drug loading, responsive release, and functional integration. Finally, challenges associated with batch-to-batch consistency, long-term biosafety, and clinical translation are discussed, together with future opportunities in AI-driven and adaptive design of metal-coordinated polysaccharide platforms.