Research Progress and Clinical Translation Prospects of Polysaccharide-Based Drugs in Anti-Hepatocellular Carcinoma Therapy

Abstract

Hepatocellular carcinoma (HCC), a highly lethal malignancy worldwide, faces significant clinical treatment challenges due to tumor heterogeneity, multidrug resistance, and therapeutic limitations. There is an urgent need for the development of novel, highly effective, and low-toxicity therapeutic agents [1]. Polysaccharides, natural macromolecular compounds widely found in plants, fungi, and marine organisms, possess advantages such as good biocompatibility, multi-target characteristics, and low toxicity, making them a significant focus in anti-HCC drug development [2]. This article systematically reviews the anti-HCC mechanisms of polysaccharide-based drugs, including direct inhibition of tumor cell proliferation, induction of apoptosis, cell cycle arrest, suppression of invasion and metastasis, as well as indirect pathways such as regulating the tumor immune microenvironment and reversing chemotherapy resistance. It elaborates on the anti-HCC activity and structural characteristics of representative polysaccharides from sources like Astragalus, Bupleurum, and Phyllanthus emblica, analyzing the regulatory role of structure-activity relationships on their bioactivity. Furthermore, it summarizes the research progress in applying polysaccharides in nano-targeted delivery systems for HCC. Key challenges hindering the clinical translation of polysaccharide-based drugs, including low bioavailability, insufficiently elucidated mechanisms, and lack of unified quality control standards, are analyzed. Finally, future research directions and clinical application prospects are discussed, aiming to provide a theoretical reference and practical basis for fundamental research and industrial development of polysaccharide-based anti-HCC drugs.