Polysaccharide-functionalized drug delivery system for metastatic cancer therapy

Most cancer-related deaths are attributed to metastatic spread rather than the primary tumors. Although existing nanomedicines have shown certain potential in the treatment of primary tumors, their effectiveness against metastatic cancer is significantly hampered by challenges such as insufficient targeting efficiency for metastatic tumor cells and inadequate modulation on the immunosuppressive microenvironment. Polysaccharides are a class of natural macromolecules with excellent biocompatibility, in vivo degradability, and low immunogenicity. Certain polysaccharides also possess unique functionalities, including specific targeting capabilities, immunomodulatory effects, etc. Leveraging the mutual recognition between polysaccharides and tumor cells, immune cells, or other biological components, a series of polysaccharide-functionalized drug delivery systems (PDDS) have been developed to intervene in tumor initiation, progression, and metastasis. This review elucidates the structures and functions of diverse polysaccharides, summarizes the main fabrication strategies for PDDS, and highlights recent advances in the applications of PDDS for metastatic cancer therapies. Furthermore, the current clinical trial landscape and challenges associated with PDDS are discussed, providing insights into future research.