Potential of polysaccharides as active targeting agents for nanoparticles toward biological receptors: a review

Polysaccharides are natural biopolymers with high biocompatibility, biodegradability, and the ability to interact with biological receptors, making them promising candidates for nanoparticle (NPs) functionalization and active drug targeting. This integrative review, conducted in the Web of Science and Scopus databases between 2020 and 2025, gathered 30 original studies on polysaccharide-functionalized NPs, highlighting their interactions with receptors such as CD44, ASGPR, GR, and FR. Hyaluronic acid (HA) was the most frequently used ligand, primarily targeting CD44. However, other biopolymers such as levan, fucoidan, and pullulan also demonstrated high affinity and selectivity. A predominance of covalent bonds, such as amide and ester linkages, was observed, contributing to chemical stability, while non-covalent interactions were mainly associated with flexibility and stimulus responsiveness. This review emphasizes the potential of polysaccharides in the design of selective, sustainable, and effective nanosystems, while also addressing challenges related to standardization, scaling-up, and regulation of essential aspects for the clinical translation of these platforms.