Colorectal cancer (CRC) remains a leading cause of cancer-related mortality worldwide, with conventional treatments such as chemotherapy often limited by systemic toxicity, poor targeting, and drug resistance. Polysaccharides, naturally derived from plants, fungi, algae, and bacteria, have emerged as promising multifaceted agents for CRC management due to their biocompatibility, biodegradability, and diverse pharmacological activities. This review comprehensively explores polysaccharide-based therapeutic strategies, highlighting their roles in immunomodulation, induction of apoptosis, suppression of inflammation and oxidative stress, and modulation of gut microbiota. Particular emphasis is placed on colon-specific drug delivery systems leveraging the resistance of polysaccharides (e.g., pectin, chitosan, dextran) to upper gastrointestinal digestion and their degradation by colonic microbiota. Advanced formulations including nanoparticles, hydrogels, microspheres, and conjugates enhance drug stability, bioavailability, and tumor targeting via passive (EPR effect) and active mechanisms while reducing off-target toxicity. Specific polysaccharides such as β-glucans, fucoidan, alginate, and modified pectin demonstrate direct anticancer effects through regulation of key signaling pathways including NF-κB, PI3K/Akt, Wnt/β-catenin, and MAPK. Preclinical studies show strong efficacy, while early clinical evidence supports their potential as adjuvants in immunotherapy and combination therapies. Despite challenges like structural variability and limited large-scale clinical trials, polysaccharides offer a versatile platform for safer, more effective CRC treatment. Future directions include standardized formulations, smart stimuli-responsive nanocarriers, and personalized approaches.
Fatima et al. (Fri,) studied this question.