As a naturally occurring marine-derived bioactive polysaccharide, fucoidan demonstrates remarkable potential in areas such as anti-tumor activity, anti-inflammatory effects, immune modulation, and gastrointestinal protection, thanks to its unique sulfate group structure and polysaccharide backbone.

As a naturally occurring bioactive polysaccharide derived from marine sources, fucoidan demonstrates remarkable potential in areas such as anti-tumor activity, anti-inflammatory effects, immune modulation, and gastrointestinal protection, thanks to its unique sulfate group structure and polysaccharide backbone. With the global aging population growing and increasing demands for health care, research on fucoidan is shifting from fundamental mechanistic exploration toward clinical translation. However, its complex molecular heterogeneity, limited bioavailability, and multi-targeted mechanisms of action still require deeper investigation. Moving forward, future studies should focus on these key areas to overcome technical barriers and expand the scope of application.

### I. In-Depth Analysis of Molecular Mechanisms and Target Networks

The biological activities of fucoidan are closely tied to its molecular structure, yet fucoidans from different sources, extracted via varying processes, and with distinct molecular weight distributions exhibit significant functional differences. For instance, fucoidan derived from kelp may inhibit tumor angiogenesis by suppressing vascular endothelial growth factor (VEGF) expression, whereas fucoidan sourced from wakame seaweed could improve metabolic syndrome by modulating gut microbiota. Moving forward, there is a need to establish a standardized structural analysis system, leveraging techniques such as mass spectrometry, nuclear magnetic resonance, and gene-editing tools, to elucidate how the positioning of sulfate groups, types of glycosidic linkages, and molecular weight distribution collectively influence fucoidan’s bioactivity.

Meanwhile, the multi-target mechanism of fucoidan remains incompletely elucidated. Its anti-tumor effects may involve activating natural killer (NK) cells, inducing apoptosis in tumor cells, and inhibiting the expression of matrix metalloproteinases (MMPs) associated with metastasis. Meanwhile, its anti-inflammatory actions are achieved by modulating the Th1/Th2 cell balance and suppressing the nuclear factor κB (NF-κB) pathway. Moving forward, it will be essential to integrate single-cell sequencing, proteomics, and metabolomics technologies to construct a comprehensive "structure-target-pathway-phenotype" interaction network, providing a solid theoretical foundation for precision intervention strategies.

### II. Enhancing Bioavailability and Developing Novel Delivery Systems

Fucoidan has a large molecular weight and is easily degraded by stomach acid, resulting in oral bioavailability of less than 10%, which severely limits its clinical applications. Currently, low-molecular-weight fucoidan (LMWF) can be produced through enzymatic or chemical degradation to enhance solubility—but this process may lead to the loss of some active functional groups. Moving forward, it will be crucial to optimize degradation techniques, such as leveraging marine microorganisms that produce highly specific fucoidanases, enabling controlled degradation while preserving the sulfate group content.

Additionally, nanodelivery technologies offer innovative approaches to enhance bioavailability. For instance, combining fucoidan with chitosan, liposomes, or metal-organic frameworks (MOFs) can create pH-responsive nanoparticles that enable targeted drug release. Mingyue Algae Group has already developed a "dynamic countercurrent" extraction technology, which, when combined with nano-encapsulation processes, boosts the stability of fucoidan in the gastrointestinal tract by more than threefold. Looking ahead, further research is needed to explore biomimetic delivery systems—such as those that mimic cell membrane structures or leverage exosome-based carriers—to improve cellular penetration capabilities even further.

### III. Clinical Translation and Multicenter Study Validation

Although fucoidan has demonstrated anti-tumor, anti-inflammatory, and immunomodulatory effects in animal studies, clinical research on the compound remains limited, primarily involving small sample sizes and single-center trials. For instance, a study conducted by Qingdao University Affiliated Hospital showed that fucoidan achieved an impressive 78% eradication rate for Helicobacter pylori infections—but long-term follow-up data are still lacking. Meanwhile, Japanese researchers found that fucoidan could reduce infection rates among elderly individuals following influenza vaccination; however, the underlying mechanisms remain unclear. Moving forward, large-scale, multi-center, randomized, double-blind, placebo-controlled trials (RCTs) are urgently needed to clarify the dose-response relationship and assess the treatment’s safety profile.

For specific diseases, it is necessary to design stratified study protocols. For instance, in adjuvant treatment for gastric cancer, combination chemotherapy drugs can be used to evaluate improvements in overall survival; while in inflammatory bowel disease, intestinal endoscopy with biopsy can help assess the extent of mucosal healing. Meanwhile, a biomarker evaluation system should be established, such as measuring serum levels of inflammatory cytokines (e.g., IL-6, TNF-α) or tumor markers (e.g., CEA, CA19-9), to quantitatively assess the therapeutic effects of fucoidan intervention.

### IV. Interdisciplinary Integration and Expansion into Emerging Fields

Research on fucoidan is shifting from focusing on a single function toward collaborative development across multiple fields. In the food industry, it can serve as a natural preservative to extend shelf life, or be combined with probiotics to create functional fermented foods. In materials science, fucoidan-based hydrogels are being explored for applications such as wound dressings or tissue-engineering scaffolds, helping to accelerate wound healing. Meanwhile, in agriculture, fucoidan has shown promise in activating plant immune systems, potentially reducing the need for chemical fertilizers.

Moving forward, it will be essential to strengthen interdisciplinary collaboration—for instance, by integrating artificial intelligence (AI) to predict the interactions between fucoidan and target proteins, or by leveraging synthetic biology techniques to engineer microorganisms for the targeted synthesis of fucoidan. Additionally, exploring fucoidan's potential role in neurodegenerative diseases, such as Alzheimer’s, could open up new therapeutic avenues—either by inhibiting β-amyloid aggregation or modulating microglial cell activity.

### Conclusion

As a "gem" of marine biological resources, fucoidan research is rapidly advancing from fundamental science toward industrial applications. Moving forward, the focus should be guided by clinical needs, addressing critical challenges such as unraveling molecular mechanisms, enhancing bioavailability, and validating findings through multi-center studies. At the same time, innovative applications in areas like functional foods, biomaterials, and precision medicine must be explored. With the growing global demand for natural bioactive compounds, fucoidan is poised to become a major driver in the health industry, offering ocean-based solutions to improve human well-being.