{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T07:19:02Z","timestamp":1793085542416,"version":"4.5.0"},"reference-count":166,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2023,2,15]],"date-time":"2023-02-15T00:00:00Z","timestamp":1676419200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Australian Government","award":["32271225"],"award-info":[{"award-number":["32271225"]}]},{"name":"Natural Science Foundation of China","award":["32271225"],"award-info":[{"award-number":["32271225"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Marine Drugs"],"abstract":"<jats:p>Fucoidans, discovered in 1913, are fucose-rich sulfated polysaccharides extracted mainly from brown seaweed. These versatile and nontoxic marine-origin heteropolysaccharides have a wide range of favorable biological activities, including antitumor, immunomodulatory, antiviral, antithrombotic, anticoagulant, antithrombotic, antioxidant, and lipid-lowering activities. In the early 1980s, fucoidans were first recognized for their role in supporting the immune response and later, in the 1990s, their effects on immune potentiation began to emerge. In recent years, the understanding of the immunomodulatory effects of fucoidan has expanded significantly. The ability of fucoidan(s) to activate CTL-mediated cytotoxicity against cancer cells, strong antitumor property, and robust safety profile make fucoidans desirable for effective cancer immunotherapy. This review focusses on current progress and understanding of the immunopotentiation activity of various fucoidans, emphasizing their relevance to cancer immunotherapy. Here, we will discuss the action of fucoidans in different immune cells and review how fucoidans can be used as adjuvants in conjunction with immunotherapeutic products to improve cancer treatment and clinical outcome. Some key rationales for the possible combination of fucoidans with immunotherapy will be discussed. An update is provided on human clinical studies and available registered cancer clinical trials using fucoidans while highlighting future prospects and challenges.<\/jats:p>","DOI":"10.3390\/md21020128","type":"journal-article","created":{"date-parts":[[2023,2,16]],"date-time":"2023-02-16T01:36:52Z","timestamp":1676511412000},"page":"128","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":49,"title":["Immunopotentiating Activity of Fucoidans and Relevance to Cancer Immunotherapy"],"prefix":"10.3390","volume":"21","author":[{"given":"Yani","family":"Li","sequence":"first","affiliation":[{"name":"School of Life Science, Faculty of Science, University of Technology Sydney, P.O. Box 123, Broadway, NSW 2007, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6371-3751","authenticated-orcid":false,"given":"Eileen","family":"McGowan","sequence":"additional","affiliation":[{"name":"School of Life Science, Faculty of Science, University of Technology Sydney, P.O. Box 123, Broadway, NSW 2007, Australia"},{"name":"Department of Immuno-Oncology, First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou 510080, China"},{"name":"Guangdong Provincial Engineering Research Center for Esophageal Cancer Precision Therapy, Guangdong Pharmaceutical University, Guangzhou 510080, China"},{"name":"Key Laboratory of Cancer Immunotherapy of Guangdong High Education Institutes, Guangdong Pharmaceutical University, Guangzhou 510080, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Size","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Immuno-Oncology, First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou 510080, China"},{"name":"Guangdong Provincial Engineering Research Center for Esophageal Cancer Precision Therapy, Guangdong Pharmaceutical University, Guangzhou 510080, China"},{"name":"Key Laboratory of Cancer Immunotherapy of Guangdong High Education Institutes, Guangdong Pharmaceutical University, Guangzhou 510080, China"},{"name":"Guangdong Provincial Key Laboratory of CAR-T Cell Therapy Associated Adverse Effect Monitoring, Guangdong Pharmaceutical University, Guangzhou 510080, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4067-220X","authenticated-orcid":false,"given":"Jerran","family":"Santos","sequence":"additional","affiliation":[{"name":"Advanced Tissue Engineering and Stem Cell Biology Group, Faculty of Science, University of Technology Sydney, P.O. Box 123, Broadway, NSW 2007, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haibin","family":"Yin","sequence":"additional","affiliation":[{"name":"Research & Development Division, Guangzhou Anjie Biomedical Technology Co., Limited, Guangzhou 510535, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4637-9701","authenticated-orcid":false,"given":"Yiguang","family":"Lin","sequence":"additional","affiliation":[{"name":"School of Life Science, Faculty of Science, University of Technology Sydney, P.O. Box 123, Broadway, NSW 2007, Australia"},{"name":"Department of Immuno-Oncology, First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou 510080, China"},{"name":"Guangdong Provincial Engineering Research Center for Esophageal Cancer Precision Therapy, Guangdong Pharmaceutical University, Guangzhou 510080, China"},{"name":"Key Laboratory of Cancer Immunotherapy of Guangdong High Education Institutes, Guangdong Pharmaceutical University, Guangzhou 510080, China"},{"name":"Guangdong Provincial Key Laboratory of CAR-T Cell Therapy Associated Adverse Effect Monitoring, Guangdong Pharmaceutical University, Guangzhou 510080, China"},{"name":"Research & Development Division, Guangzhou Anjie Biomedical Technology Co., Limited, Guangzhou 510535, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,2,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1186\/s12935-020-01233-8","article-title":"The anti-cancer effects of fucoidan: A review of both in vivo and in vitro investigations","volume":"20","author":"Lin","year":"2020","journal-title":"Cancer Cell Int."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Tomori, M., Nagamine, T., Miyamoto, T., and Iha, M. (2019). Evaluation of the Immunomodulatory Effects of Fucoidan Derived from Cladosiphon Okamuranus Tokida in Mice. Mar. Drugs, 17.","DOI":"10.3390\/md17100547"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Sanjeewa, K.K.A., Herath, K.H.I.N.M., Yang, H.-W., Choi, C.S., and Jeon, Y.-J. (2021). Anti-Inflammatory Mechanisms of Fucoidans to Treat Inflammatory Diseases: A Review. Mar. Drugs, 19.","DOI":"10.3390\/md19120678"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Apostolova, E., Lukova, P., Baldzhieva, A., Katsarov, P., Nikolova, M., Iliev, I., Peychev, L., Trica, B., Oancea, F., and Delattre, C. (2020). Immunomodulatory and Anti-Inflammatory Effects of Fucoidan: A Review. Polymers, 12.","DOI":"10.3390\/polym12102338"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Kiselevskiy, M.V., Anisimova, N.Y., Ustyuzhanina, N.E., Vinnitskiy, D.Z., Tokatly, A.I., Reshetnikova, V.V., Chikileva, I.O., Shubina, I.Z., Kirgizov, K.I., and Nifantiev, N.E. (2022). Perspectives for the Use of Fucoidans in Clinical Oncology. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms231911821"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"606","DOI":"10.1016\/j.carbpol.2013.02.047","article-title":"Fucoidan from New Zealand Undaria pinnatifida: Monthly variations and determination of antioxidant activities","volume":"95","author":"Mak","year":"2013","journal-title":"Carbohydr. Polym."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1016\/j.ijbiomac.2009.10.015","article-title":"Potential antioxidant and anticoagulant capacity of low molecular weight fucoidan fractions extracted from Laminaria japonica","volume":"46","author":"Wang","year":"2010","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1671","DOI":"10.3390\/molecules13081671","article-title":"Fucoidan: Structure and bioactivity","volume":"13","author":"Li","year":"2008","journal-title":"Molecules"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Priyanka, K.R., Rajaram, R., and Sivakumar, S.R. (2022). A critical review on pharmacological properties of marine macroalgae. Biomass Convers. Biorefinery.","DOI":"10.1007\/s13399-022-03134-4"},{"key":"ref_10","unstructured":"Agency, E.M. (2014). Assessment Report on Fucus vesiculosus L., thallus, European Medicines Agency."},{"key":"ref_11","unstructured":"Kylin, H. (2022, December 15). Zur Biochemie der Meeresalgen. Available online: https:\/\/www.degruyter.com\/document\/doi\/10.1515\/bchm2.1913.83.3.171\/html."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1186\/s40169-019-0234-9","article-title":"Clinical applications of fucoidan in translational medicine for adjuvant cancer therapy","volume":"8","author":"Hsu","year":"2019","journal-title":"Clin. Transl. Med."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1111\/j.1469-8137.2010.03374.x","article-title":"The cell wall polysaccharide metabolism of the brown alga Ectocarpus siliculosus. Insights into the evolution of extracellular matrix polysaccharides in Eukaryotes","volume":"188","author":"Michel","year":"2010","journal-title":"New Phytol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"29R","DOI":"10.1093\/glycob\/cwg058","article-title":"Sulfated fucans, fresh perspectives: Structures, functions, and biological properties of sulfated fucans and an overview of enzymes active toward this class of polysaccharide","volume":"13","author":"Berteau","year":"2003","journal-title":"Glycobiology"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1016\/j.carbpol.2017.07.082","article-title":"A review about brown algal cell walls and fucose-containing sulfated polysaccharides: Cell wall context, biomedical properties and key research challenges","volume":"175","author":"Hardouin","year":"2017","journal-title":"Carbohydr. Polym."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"556312","DOI":"10.3389\/fpls.2020.556312","article-title":"A Comprehensive and Comparative Analysis of the Fucoidan Compositional Data Across the Phaeophyceae","volume":"11","author":"Ponce","year":"2020","journal-title":"Front. Plant Sci."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Obluchinskaya, E.D., Pozharitskaya, O.N., and Shikov, A.N. (2022). In Vitro Anti-Inflammatory Activities of Fucoidans from Five Species of Brown Seaweeds. Mar. Drugs, 20.","DOI":"10.3390\/md20100606"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"733246","DOI":"10.3389\/fcell.2021.733246","article-title":"Fucoidan-Supplemented Diet Potentiates Immune Checkpoint Blockage by Enhancing Antitumor Immunity","volume":"9","author":"Yang","year":"2021","journal-title":"Front. Cell Dev. Biol."},{"key":"ref_19","unstructured":"Fucoidan, N.R.I.O. (2023, February 03). High-Molecular Weight Fucoidan & Low-Molecular Weight Fucoidan. Available online: https:\/\/www.fucoidan-life.com\/en\/info_fucoidan\/fucoidan\/."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"109625","DOI":"10.1016\/j.biopha.2019.109625","article-title":"PD-1 disrupted CAR-T cells in the treatment of solid tumors: Promises and challenges","volume":"121","author":"McGowan","year":"2020","journal-title":"Biomed. Pharmacother."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1772663","DOI":"10.1080\/2162402X.2020.1772663","article-title":"Cancer immunotherapy using a polysaccharide from Codium fragile in a murine model","volume":"9","author":"Park","year":"2020","journal-title":"Oncoimmunology"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"941","DOI":"10.1016\/j.ijbiomac.2020.05.160","article-title":"Dendritic cell-mediated cancer immunotherapy with Ecklonia cava fucoidan","volume":"159","author":"Park","year":"2020","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Zhang, W., Hwang, J., Yadav, D., An, E.-K., Kwak, M., Lee, P.C.-W., and Jin, J.-O. (2021). Enhancement of Immune Checkpoint Inhibitor-Mediated Anti-Cancer Immunity by Intranasal Treatment of Ecklonia cava Fucoidan against Metastatic Lung Cancer. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22179125"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1177\/1534735416684014","article-title":"The Effect of Undaria pinnatifida Fucoidan on the Pharmacokinetics of Letrozole and Tamoxifen in Patients With Breast Cancer","volume":"17","author":"Tocaciu","year":"2018","journal-title":"Integr. Cancer Ther."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1362","DOI":"10.1515\/biolog-2017-0158","article-title":"Fucoidan from Undaria pinnatifida regulates type II collagen and COX-2 expression via MAPK and PI3K pathways in rabbit articular chondrocytes","volume":"72","author":"Phull","year":"2017","journal-title":"Biologia"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Zhao, Y., Zheng, Y., Wang, J., Ma, S., Yu, Y., White, W.L., Yang, S., Yang, F., and Lu, J. (2018). Fucoidan Extracted from Undaria pinnatifida: Source for Nutraceuticals\/Functional Foods. Mar. Drugs, 16.","DOI":"10.3390\/md16090321"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1016\/j.ijbiomac.2010.05.010","article-title":"Structural studies on a novel fucogalactan sulfate extracted from the brown seaweed Laminaria japonica","volume":"47","author":"Wang","year":"2010","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1421","DOI":"10.1016\/j.ijbiomac.2017.07.148","article-title":"The structure property and endothelial protective activity of fucoidan from Laminaria japonica","volume":"105","author":"Chen","year":"2017","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"2106","DOI":"10.3390\/md9102106","article-title":"Important Determinants for Fucoidan Bioactivity: A Critical Review of Structure-Function Relations and Extraction Methods for Fucose-Containing Sulfated Polysaccharides from Brown Seaweeds","volume":"9","author":"Ale","year":"2011","journal-title":"Mar. Drugs"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s00253-008-1790-x","article-title":"Fucoidans and fucoidanases\u2014Focus on techniques for molecular structure elucidation and modification of marine polysaccharides","volume":"82","author":"Holtkamp","year":"2009","journal-title":"Appl. Microbiol. Biotechnol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1016\/j.algal.2016.10.015","article-title":"The seasonal variation of fucoidan within three species of brown macroalgae","volume":"22","author":"Fletcher","year":"2017","journal-title":"Algal Res."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1600340","DOI":"10.1002\/mabi.201600340","article-title":"The Key Role of Sulfation and Branching on Fucoidan Antitumor Activity","volume":"17","author":"Oliveira","year":"2017","journal-title":"Macromol. Biosci."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1271\/bbb.120631","article-title":"Induction of apoptosis by low-molecular-weight fucoidan through calcium- and caspase-dependent mitochondrial pathways in MDA-MB-231 breast cancer cells","volume":"77","author":"Zhang","year":"2013","journal-title":"Biosci. Biotechnol. Biochem."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1093\/glycob\/cwm014","article-title":"A comparative study of the anti-inflammatory, anticoagulant, antiangiogenic, and antiadhesive activities of nine different fucoidans from brown seaweeds","volume":"17","author":"Cumashi","year":"2007","journal-title":"Glycobiology"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Liu, L., Yang, X., Yuan, P., Cai, S., Bao, J., Zhao, Y., Aimaier, A., Aipire, A., Lu, J., and Li, J. (2022). In Vitro and In Vivo Dendritic Cell Immune Stimulation Effect of Low Molecular Weight Fucoidan from New Zealand Undaria pinnatifida. Mar. Drugs, 20.","DOI":"10.3390\/md20030197"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"562","DOI":"10.1016\/j.ijbiomac.2022.09.201","article-title":"Fucoidan, as an immunostimulator promotes M1 macrophage differentiation and enhances the chemotherapeutic sensitivity of capecitabine in colon cancer","volume":"222","author":"Deng","year":"2022","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"21770","DOI":"10.1016\/S0021-9258(20)80609-7","article-title":"A revised structure for fucoidan may explain some of its biological activities","volume":"268","author":"Patankar","year":"1993","journal-title":"J. Biol. Chem."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Chollet, L., Saboural, P., Chauvierre, C., Villemin, J.N., Letourneur, D., and Chaubet, F. (2016). Fucoidans in Nanomedicine. Mar. Drugs, 14.","DOI":"10.3390\/md14080145"},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Zayed, A., El-Aasr, M., Ibrahim, A.S., and Ulber, R. (2020). Fucoidan Characterization: Determination of Purity and Physicochemical and Chemical Properties. Mar. Drugs, 18.","DOI":"10.3390\/md18110571"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1016\/S0008-6215(99)00127-5","article-title":"Further data on the structure of brown seaweed fucans: Relationships with anticoagulant activity","volume":"319","author":"Chevolot","year":"1999","journal-title":"Carbohydr. Res."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Luthuli, S., Wu, S., Cheng, Y., Zheng, X., Wu, M., and Tong, H. (2019). Therapeutic Effects of Fucoidan: A Review on Recent Studies. Mar. Drugs, 17.","DOI":"10.3390\/md17090487"},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Citkowska, A., Szekalska, M., and Winnicka, K. (2019). Possibilities of Fucoidan Utilization in the Development of Pharmaceutical Dosage Forms. Mar. Drugs, 17.","DOI":"10.3390\/md17080458"},{"key":"ref_43","unstructured":"Qin, Y. (2018). Bioactive Seaweeds for Food Applications, Academic Press."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1016\/S0008-6215(00)90980-7","article-title":"Isolation and partial characterization of a noval amino sugar-containing fucan sulfate from commercial Fucus vesiculosus fucoidan","volume":"255","author":"Nishino","year":"1994","journal-title":"Carbohydr. Res."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1880","DOI":"10.1021\/acsabm.8b00436","article-title":"Structural Characterization of Fucoidan from Laminaria hyperborea: Assessment of Coagulation and Inflammatory Properties and Their Structure\u2013Function Relationship","volume":"1","author":"Kopplin","year":"2018","journal-title":"ACS Appl. Bio Mater."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1265","DOI":"10.1093\/glycob\/cwu063","article-title":"Fucoidans: Pro- or antiangiogenic agents?","volume":"24","author":"Ustyuzhanina","year":"2014","journal-title":"Glycobiology"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"994","DOI":"10.1016\/j.ijbiomac.2021.06.182","article-title":"Influence of molecular weight fractionation on the antimicrobial and anticancer properties of a fucoidan rich-extract from the macroalgae Fucus vesiculosus","volume":"186","author":"Cabral","year":"2021","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Yang, X., Wang, S., Trangle, S.S., Li, Y., White, W.L., Li, J., Ying, T., Kong, Q., Zhao, Y., and Lu, J. (2018). Investigation of Different Molecular Weight Fucoidan Fractions Derived from New Zealand Undaria pinnatifida in Combination with GroA Therapy in Prostate Cancer Cell Lines. Mar. Drugs, 16.","DOI":"10.3390\/md16110454"},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Yoo, H.J., You, D.J., and Lee, K.W. (2019). Characterization and Immunomodulatory Effects of High Molecular Weight Fucoidan Fraction from the Sporophyll of Undaria pinnatifida in Cyclophosphamide-Induced Immunosuppressed Mice. Mar. Drugs, 17.","DOI":"10.3390\/md17080447"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1016\/S0008-6215(00)00314-1","article-title":"A disaccharide repeat unit is the major structure in fucoidans from two species of brown algae","volume":"330","author":"Chevolot","year":"2001","journal-title":"Carbohydr. Res."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"719","DOI":"10.1016\/S0008-6215(02)00053-8","article-title":"Structure of a fucoidan from the brown seaweed Fucus evanescens C.Ag","volume":"337","author":"Bilan","year":"2002","journal-title":"Carbohydr. Res."},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Lu, J., Shi, K.K., Chen, S., Wang, J., Hassouna, A., White, L.N., Merien, F., Xie, M., Kong, Q., and Li, J. (2018). Fucoidan Extracted from the New Zealand Undaria pinnatifida-Physicochemical Comparison against Five Other Fucoidans: Unique Low Molecular Weight Fraction Bioactivity in Breast Cancer Cell Lines. Mar. Drugs, 16.","DOI":"10.3390\/md16120461"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"9","DOI":"10.3389\/fnut.2014.00009","article-title":"Anti-Proliferation Potential and Content of Fucoidan Extracted from Sporophyll of New Zealand Undaria pinnatifida","volume":"1","author":"Mak","year":"2014","journal-title":"Front. Nutr."},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"van Weelden, G., Bobinski, M., Okla, K., van Weelden, W.J., Romano, A., and Pijnenborg, J.M.A. (2019). Fucoidan Structure and Activity in Relation to Anti-Cancer Mechanisms. Mar. Drugs, 17.","DOI":"10.3390\/md17010032"},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Jin, J.O., Chauhan, P.S., Arukha, A.P., Chavda, V., Dubey, A., and Yadav, D. (2021). The Therapeutic Potential of the Anticancer Activity of Fucoidan: Current Advances and Hurdles. Mar. Drugs, 19.","DOI":"10.3390\/md19050265"},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Jin, J.O., Yadav, D., Madhwani, K., Puranik, N., Chavda, V., and Song, M. (2022). Seaweeds in the Oncology Arena: Anti-Cancer Potential of Fucoidan as a Drug-A Review. Molecules, 27.","DOI":"10.3390\/molecules27186032"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1016\/j.apsb.2021.05.012","article-title":"Fucoidan-functionalized activated platelet-hitchhiking micelles simultaneously track tumor cells and remodel the immunosuppressive microenvironment for efficient metastatic cancer treatment","volume":"12","author":"Guo","year":"2022","journal-title":"Acta Pharm. Sin. B"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"101884","DOI":"10.1016\/j.algal.2020.101884","article-title":"Antitumoral effects of fucoidan on bladder cancer","volume":"47","author":"Pacheco","year":"2020","journal-title":"Algal Res."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1160\/TH13-08-0635","article-title":"Structure-activity relationship of the pro- and anticoagulant effects of Fucus vesiculosus fucoidan","volume":"111","author":"Zhang","year":"2014","journal-title":"Thromb. Haemost."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1145","DOI":"10.1016\/j.ijbiomac.2018.10.129","article-title":"Primary structure and anticoagulant activity of fucoidan from the sea cucumber Holothuria polii","volume":"121","author":"Mansour","year":"2019","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1016\/j.ijbiomac.2007.10.023","article-title":"Characterization of a fucoidan from Lessonia vadosa (Phaeophyta) and its anticoagulant and elicitor properties","volume":"42","author":"Matsuhiro","year":"2008","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.carbpol.2012.07.067","article-title":"A comparative study of the anticoagulant activities of eleven fucoidans","volume":"91","author":"Jin","year":"2013","journal-title":"Carbohydr. Polym."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"3618","DOI":"10.1016\/S0021-9258(18)94111-6","article-title":"Antithrombin Activity of Fucoidan: The interaction of fucoidan with heparin cofactor II, antithrombin III, and thrombin","volume":"264","author":"Church","year":"1989","journal-title":"J. Biol. Chem."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1016\/S0167-4838(98)00120-4","article-title":"Mechanism of factor IXa inhibition by antithrombin in the presence of unfractionated and low molecular weight heparins and fucoidan","volume":"1387","author":"Mauray","year":"1998","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1333","DOI":"10.1016\/j.bbrc.2014.06.137","article-title":"Fucoidan\/FGF-2 induces angiogenesis through JNK- and p38-mediated activation of AKT\/MMP-2 signalling","volume":"450","author":"Kim","year":"2014","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"899","DOI":"10.1016\/j.carbpol.2015.09.087","article-title":"Structural characterization and effect on anti-angiogenic activity of a fucoidan from Sargassum fusiforme","volume":"136","author":"Cong","year":"2016","journal-title":"Carbohydr. Polym."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1016\/S0049-3848(02)00136-6","article-title":"Effect of fucoidan on fibroblast growth factor-2-induced angiogenesis in vitro","volume":"106","author":"Matou","year":"2002","journal-title":"Thromb. Res."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1016\/j.thromres.2004.01.013","article-title":"Low molecular weight fucoidan promotes FGF-2-induced vascular tube formation by human endothelial cells, with decreased PAI-1 release and ICAM-1 downregulation","volume":"113","author":"Chabut","year":"2004","journal-title":"Thromb. Res."},{"key":"ref_69","first-page":"695","article-title":"Effects of middle molecular weight fucoidans on in vitro and ex vivo angiogenesis of endothelial cells","volume":"15","author":"Matsubara","year":"2005","journal-title":"Int. J. Mol. Med."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/j.ijbiomac.2015.09.078","article-title":"In vitro anti-HIV-1 activity of fucoidan from Sargassum swartzii","volume":"82","author":"Dinesh","year":"2016","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"1016","DOI":"10.1093\/glycob\/cwn085","article-title":"Structure, biology, evolution, and medical importance of sulfated fucans and galactans","volume":"18","author":"Pomin","year":"2008","journal-title":"Glycobiology"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1016\/j.intimp.2007.10.017","article-title":"Defensive effects of a fucoidan from brown alga Undaria pinnatifida against herpes simplex virus infection","volume":"8","author":"Hayashi","year":"2008","journal-title":"Int. Immunopharmacol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"705","DOI":"10.1007\/s11802-018-3794-1","article-title":"Studies on Antiviral and Immuno-Regulation Activity of Low Molecular Weight Fucoidan from Laminaria japonica","volume":"17","author":"Sun","year":"2018","journal-title":"J. Ocean Univ. China"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"7415","DOI":"10.1039\/D0FO02017F","article-title":"Inhibitory activities of marine sulfated polysaccharides against SARS-CoV-2","volume":"11","author":"Song","year":"2020","journal-title":"Food Funct."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"1885","DOI":"10.1016\/j.ijbiomac.2021.11.020","article-title":"Nanoparticular CpG-adjuvanted SARS-CoV-2 S1 protein elicits broadly neutralizing and Th1-biased immunoreactivity in mice","volume":"193","author":"Lin","year":"2021","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"2327","DOI":"10.3390\/md13042327","article-title":"Fucoidan and cancer: A multifunctional molecule with anti-tumor potential","volume":"13","author":"Atashrazm","year":"2015","journal-title":"Mar. Drugs"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"851","DOI":"10.3390\/md12020851","article-title":"Fucoidan as a Marine Anticancer Agent in Preclinical Development","volume":"12","author":"Kwak","year":"2014","journal-title":"Mar. Drugs"},{"key":"ref_78","first-page":"143","article-title":"Antitumor effect of seaweeds. IV. Enhancement of antitumor activity by sulfation of a crude fucoidan fraction from Sargassum kjellmanianum","volume":"54","author":"Yamamoto","year":"1984","journal-title":"Jpn. J. Exp. Med."},{"key":"ref_79","doi-asserted-by":"crossref","unstructured":"Zhang, Z., Teruya, K., Eto, H., and Shirahata, S. (2011). Fucoidan Extract Induces Apoptosis in MCF-7 Cells via a Mechanism Involving the ROS-Dependent JNK Activation and Mitochondria-Mediated Pathways. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0027441"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"8677","DOI":"10.1021\/jf9010406","article-title":"Fucoidan induces apoptosis through activation of caspase-8 on human breast cancer MCF-7 cells","volume":"57","author":"Yamasaki","year":"2009","journal-title":"J. Agric. Food Chem."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"748","DOI":"10.2174\/1389201018666171115115112","article-title":"Effects of Fucoidan and Chemotherapeutic Agent Combinations on Malignant and Non-malignant Breast Cell Lines","volume":"18","author":"Abudabbus","year":"2017","journal-title":"Curr. Pharm. Biotechnol."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"987","DOI":"10.1007\/s12272-021-01355-1","article-title":"Advances in plant-derived natural products for antitumor immunotherapy","volume":"44","author":"Yang","year":"2021","journal-title":"Arch. Pharm. Res."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"717","DOI":"10.1007\/s11596-013-1186-8","article-title":"Fucoidan induces G1 phase arrest and apoptosis through caspases-dependent pathway and ROS induction in human breast cancer MCF-7 cells","volume":"33","author":"Banafa","year":"2013","journal-title":"J. Huazhong Univ. Sci. Technol. Med. Sci."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"1082","DOI":"10.1002\/ptr.3489","article-title":"Fucoidan from Undaria pinnatifida induces apoptosis in A549 human lung carcinoma cells","volume":"25","author":"Boo","year":"2011","journal-title":"Phytother. Res."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1016\/j.canlet.2018.05.006","article-title":"Fucoidan upregulates TLR4\/CHOP-mediated caspase-3 and PARP activation to enhance cisplatin-induced cytotoxicity in human lung cancer cells","volume":"432","author":"Hsu","year":"2018","journal-title":"Cancer Lett."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"44990","DOI":"10.1038\/srep44990","article-title":"Fucoidan induces Toll-like receptor 4-regulated reactive oxygen species and promotes endoplasmic reticulum stress-mediated apoptosis in lung cancer","volume":"7","author":"Hsu","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_87","doi-asserted-by":"crossref","unstructured":"(2021). Chen, X.; Sun, L.; Wei, X.; Lu, H.; Tan, Y.; Sun, Z.; Jiang, J. Antitumor effect and molecular mechanism of fucoidan in NSCLC. BMC Complement Med., 21.","DOI":"10.1186\/s12906-020-03191-0"},{"key":"ref_88","doi-asserted-by":"crossref","unstructured":"Lee, H., Kim, J.S., and Kim, E. (2012). Fucoidan from seaweed Fucus vesiculosus inhibits migration and invasion of human lung cancer cell via PI3K-Akt-mTOR pathways. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0050624"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"81","DOI":"10.3390\/md11010081","article-title":"Fucoidan extract enhances the anti-cancer activity of chemotherapeutic agents in MDA-MB-231 and MCF-7 breast cancer cells","volume":"11","author":"Zhang","year":"2013","journal-title":"Mar. Drugs"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1016\/j.canlet.2016.08.020","article-title":"Sulfated fucoidan FP08S2 inhibits lung cancer cell growth in vivo by disrupting angiogenesis via targeting VEGFR2\/VEGF and blocking VEGFR2\/Erk\/VEGF signaling","volume":"382","author":"Chen","year":"2016","journal-title":"Cancer Lett."},{"key":"ref_91","doi-asserted-by":"crossref","unstructured":"Danforth, D.N. (2021). The Role of Chronic Inflammation in the Development of Breast Cancer. Cancers, 13.","DOI":"10.3390\/cancers13153918"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.mrrev.2008.03.002","article-title":"Inflammation: Gearing the journey to cancer","volume":"659","author":"Kundu","year":"2008","journal-title":"Mutat. Res.\/Rev. Mutat. Res."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1016\/j.bbrc.2010.01.018","article-title":"Fucoidin enhances dendritic cell-mediated T-cell cytotoxicity against NY-ESO-1 expressing human cancer cells","volume":"392","author":"Hu","year":"2010","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_94","doi-asserted-by":"crossref","unstructured":"Jin, J.O., Zhang, W., Du, J.Y., Wong, K.W., Oda, T., and Yu, Q. (2014). Fucoidan can function as an adjuvant in vivo to enhance dendritic cell maturation and function and promote antigen-specific T cell immune responses. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0099396"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"10721","DOI":"10.1021\/acs.jafc.8b03698","article-title":"Immune Activation of RAW264.7 Macrophages by Low Molecular Weight Fucoidan Extracted from New Zealand Undaria pinnatifida","volume":"66","author":"Bi","year":"2018","journal-title":"J. Agric. Food Chem."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1007\/s13273-017-0045-2","article-title":"Fucoidan inhibits lipopolysaccharide-induced inflammatory responses in RAW 264.7 macrophages and zebrafish larvae","volume":"13","author":"Jeong","year":"2017","journal-title":"Mol. Cell. Toxicol."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"717","DOI":"10.1016\/j.ijbiomac.2020.04.012","article-title":"In vitro and in vivo anti-inflammatory activities of a fucose-rich fucoidan isolated from Saccharina japonica","volume":"156","author":"Ni","year":"2020","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"98","DOI":"10.3389\/fimmu.2011.00098","article-title":"Chronic inflammation in cancer development","volume":"2","author":"Multhoff","year":"2012","journal-title":"Front. Immunol."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1016\/j.carbpol.2012.03.056","article-title":"Molecular characteristics and anti-inflammatory activity of the fucoidan extracted from Ecklonia cava","volume":"89","author":"Lee","year":"2012","journal-title":"Carbohydr. Polym."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"1185","DOI":"10.1016\/j.ijbiomac.2017.07.031","article-title":"A fucoidan fraction purified from Chnoospora minima; a potential inhibitor of LPS-induced inflammatory responses","volume":"104","author":"Fernando","year":"2017","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"803","DOI":"10.1016\/j.ijbiomac.2017.09.050","article-title":"In vitro and in vivo anti-inflammatory activities of high molecular weight sulfated polysaccharide; containing fucose separated from Sargassum horneri: Short communication","volume":"107","author":"Sanjeewa","year":"2018","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"3","DOI":"10.4162\/nrp.2017.11.1.3","article-title":"Anti-inflammatory activity of a sulfated polysaccharide isolated from an enzymatic digest of brown seaweed Sargassum horneri in RAW 264.7 cells","volume":"11","author":"Sanjeewa","year":"2017","journal-title":"Nutr. Res. Pract."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1016\/j.yjmcc.2016.05.011","article-title":"Fucoidan improves bioactivity and vasculogenic potential of mesenchymal stem cells in murine hind limb ischemia associated with chronic kidney disease","volume":"97","author":"Lee","year":"2016","journal-title":"J. Mol. Cell. Cardiol."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"1115","DOI":"10.1016\/j.ijbiomac.2018.12.014","article-title":"Development of methotrexate loaded fucoidan\/chitosan nanoparticles with anti-inflammatory potential and enhanced skin permeation","volume":"124","author":"Barbosa","year":"2019","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_105","doi-asserted-by":"crossref","unstructured":"Ahmad, T., Eapen, M.S., Ishaq, M., Park, A.Y., Karpiniec, S.S., Stringer, D.N., Sohal, S.S., Fitton, J.H., Guven, N., and Caruso, V. (2021). Anti-Inflammatory Activity of Fucoidan Extracts In Vitro. Mar. Drugs, 19.","DOI":"10.3390\/md19120702"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1016\/j.rvsc.2018.04.007","article-title":"Fucoidan suppresses excessive phagocytic capacity of porcine peripheral blood polymorphonuclear cells by modulating production of tumor necrosis factor-alpha by lipopolysaccharide-stimulated peripheral blood mononuclear cells","volume":"118","author":"Kim","year":"2018","journal-title":"Res. Vet. Sci."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"32033","DOI":"10.3402\/fnr.v60.32033","article-title":"Low-molecular-weight fucoidan and high-stability fucoxanthin from brown seaweed exert prebiotics and anti-inflammatory activities in Caco-2 cells","volume":"60","author":"Hwang","year":"2016","journal-title":"Food Nutr. Res."},{"key":"ref_108","doi-asserted-by":"crossref","unstructured":"Fernando, I.P.S., Sanjeewa, K.K.A., Lee, H.G., Kim, H.S., Vaas, A., De Silva, H.I.C., Nanayakkara, C.M., Abeytunga, D.T.U., Lee, D.S., and Lee, J.S. (2020). Fucoidan Purified from Sargassum polycystum Induces Apoptosis through Mitochondria-Mediated Pathway in HL-60 and MCF-7 Cells. Mar Drugs, 18.","DOI":"10.3390\/md18040196"},{"key":"ref_109","doi-asserted-by":"crossref","unstructured":"Wang, Y., Xing, M., Cao, Q., Ji, A., Liang, H., and Song, S. (2019). Biological Activities of Fucoidan and the Factors Mediating Its Therapeutic Effects: A Review of Recent Studies. Mar. Drugs, 17.","DOI":"10.3390\/md17030183"},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1016\/j.carbpol.2019.02.040","article-title":"Structure characterization and antioxidant activity of fucoidan isolated from Undaria pinnatifida grown in New Zealand","volume":"212","author":"Koh","year":"2019","journal-title":"Carbohydr. Polym."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"552","DOI":"10.1039\/C7FO00662D","article-title":"Fucoidan inhibits amyloid-\u03b2-induced toxicity in transgenic Caenorhabditis elegans by reducing the accumulation of amyloid-\u03b2 and decreasing the production of reactive oxygen species","volume":"9","author":"Wang","year":"2018","journal-title":"Food Funct."},{"key":"ref_112","doi-asserted-by":"crossref","unstructured":"Pozharitskaya, O.N., Shikov, A.N., Faustova, N.M., Obluchinskaya, E.D., Kosman, V.M., Vuorela, H., and Makarov, V.G. (2018). Pharmacokinetic and Tissue Distribution of Fucoidan from Fucus vesiculosus after Oral Administration to Rats. Mar. Drugs, 16.","DOI":"10.3390\/md16040132"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1016\/j.thromres.2016.03.008","article-title":"Antithrombotic activity of oral administered low molecular weight fucoidan from Laminaria Japonica","volume":"144","author":"Zhao","year":"2016","journal-title":"Thromb. Res."},{"key":"ref_114","first-page":"1","article-title":"Determination of fucoidan in rat plasma by HPLC and its application in pharmacokinetics","volume":"33","author":"Zhan","year":"2020","journal-title":"Pak. J. Pharm. Sci."},{"key":"ref_115","doi-asserted-by":"crossref","unstructured":"Shikov, A.N., Flisyuk, E.V., Obluchinskaya, E.D., and Pozharitskaya, O.N. (2020). Pharmacokinetics of Marine-Derived Drugs. Mar. Drugs, 18.","DOI":"10.3390\/md18110557"},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"350","DOI":"10.1271\/bbb.90705","article-title":"Development of a fucoidan-specific antibody and measurement of fucoidan in serum and urine by sandwich ELISA","volume":"74","author":"Tokita","year":"2010","journal-title":"Biosci. Biotechnol. Biochem."},{"key":"ref_117","doi-asserted-by":"crossref","unstructured":"Kadena, K., Tomori, M., Iha, M., and Nagamine, T. (2018). Absorption Study of Mozuku Fucoidan in Japanese Volunteers. Mar. Drugs, 16.","DOI":"10.3390\/md16080254"},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1007\/s00343-015-4273-9","article-title":"Microanalysis and preliminary pharmacokinetic studies of a sulfated polysaccharide from Laminaria japonica","volume":"34","author":"Zhang","year":"2016","journal-title":"Chin. J. Oceanol. Limnol."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"778","DOI":"10.1016\/j.ijbiomac.2019.10.018","article-title":"Is the transformation of fucoidans in human body possible?","volume":"142","author":"Imbs","year":"2020","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_120","doi-asserted-by":"crossref","unstructured":"Bai, X., Zhang, E., Hu, B., Liang, H., Song, S., and Ji, A. (2020). Study on Absorption Mechanism and Tissue Distribution of Fucoidan. Molecules, 25.","DOI":"10.3390\/molecules25051087"},{"key":"ref_121","unstructured":"Marinova Pty. Ltd. (2016). Determination of the Generally Recognized as Safe (Gras) Status of Fucoidan from Fucus Vesiculosus as a Food Ingredient."},{"key":"ref_122","doi-asserted-by":"crossref","unstructured":"Fitton, H.J., Stringer, D.S., Park, A.Y., and Karpiniec, S.N. (2019). Therapies from Fucoidan: New Developments. Mar. Drugs, 17.","DOI":"10.3390\/md17100571"},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1016\/0008-8749(82)90016-8","article-title":"Polysaccharides with sulfate groups are human T-cell mitogens and murine polyclonal B-cell activators (PBAs). I. Fucoidan and heparin","volume":"74","author":"Sugawara","year":"1982","journal-title":"Cell. Immunol."},{"key":"ref_124","first-page":"9","article-title":"[Antibacterial and immunomodulating activity of fucoidan]","volume":"40","author":"Zapopozhets","year":"1995","journal-title":"Antibiot. Khimioter."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1016\/S0192-0561(97)00016-7","article-title":"B cell stimulating activity of seaweed extracts","volume":"19","author":"Liu","year":"1997","journal-title":"Int. J. Immunopharmacol."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"746","DOI":"10.1038\/s41565-018-0146-7","article-title":"Combination of fucoidan-based magnetic nanoparticles and immunomodulators enhances tumour-localized immunotherapy","volume":"13","author":"Chiang","year":"2018","journal-title":"Nat. Nanotechnol."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"1084","DOI":"10.3390\/md13031084","article-title":"Fucoidan from Macrocystis pyrifera Has Powerful Immune-Modulatory Effects Compared to Three Other Fucoidans","volume":"13","author":"Zhang","year":"2015","journal-title":"Mar. Drugs"},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1016\/j.ijbiomac.2020.01.125","article-title":"The activation of NF-\u03baB and MAPKs signaling pathways of RAW264.7 murine macrophages and natural killer cells by fucoidan from Nizamuddinia zanardinii","volume":"148","author":"Tabarsa","year":"2020","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1016\/j.ijbiomac.2011.05.009","article-title":"Fucoidan from Sargassum sp. and Fucus vesiculosus reduces cell viability of lung carcinoma and melanoma cells in vitro and activates natural killer cells in mice in vivo","volume":"49","author":"Ale","year":"2011","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1016\/j.ijbiomac.2021.06.045","article-title":"Ecklonia cava fucoidan has potential to stimulate natural killer cells in vivo","volume":"185","author":"Zhang","year":"2021","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"1754","DOI":"10.1016\/j.intimp.2008.08.007","article-title":"Fucoidan stimulation induces a functional maturation of human monocyte-derived dendritic cells","volume":"8","author":"Yang","year":"2008","journal-title":"Int. Immunopharmacol."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"5839","DOI":"10.1182\/blood-2008-10-184796","article-title":"Ligand of scavenger receptor class A indirectly induces maturation of human blood dendritic cells via production of tumor necrosis factor-alpha","volume":"113","author":"Jin","year":"2009","journal-title":"Blood"},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"35855","DOI":"10.1038\/srep35855","article-title":"Fucoidan inhibits CCL22 production through NF-\u03baB pathway in M2 macrophages: A potential therapeutic strategy for cancer","volume":"6","author":"Sun","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1007\/s10517-012-1922-2","article-title":"Interactions between sulfated polysaccharides from sea brown algae and Toll-like receptors on HEK293 eukaryotic cells in vitro","volume":"154","author":"Makarenkova","year":"2012","journal-title":"Bull. Exp. Biol. Med."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"439","DOI":"10.4014\/jmb.1908.08026","article-title":"Undaria pinnatifida Fucoidan-Rich Extract Recovers Immunity of Immunosuppressed Mice","volume":"30","author":"Lee","year":"2020","journal-title":"J. Microbiol. Biotechnol."},{"key":"ref_136","doi-asserted-by":"crossref","unstructured":"Park, A.Y., Nafia, I., Stringer, D.N., Karpiniec, S.S., and Fitton, J.H. (2022). Fucoidan Independently Enhances Activity in Human Immune Cells and Has a Cytostatic Effect on Prostate Cancer Cells in the Presence of Nivolumab. Mar. Drugs, 20.","DOI":"10.3390\/md20010012"},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"286","DOI":"10.1016\/j.bbrc.2006.02.146","article-title":"Fucoidan induces nitric oxide production via p38 mitogen-activated protein kinase and NF-\u03baB-dependent signaling pathways through macrophage scavenger receptors","volume":"343","author":"Nakamura","year":"2006","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1016\/j.fct.2014.03.024","article-title":"Differential effects of fucoidans with low and high molecular weight on the viability and function of spleen cells","volume":"68","author":"Jang","year":"2014","journal-title":"Food Chem. Toxicol."},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/j.smim.2003.10.004","article-title":"Toll-like receptors and dendritic cells: For whom the bug tolls","volume":"16","year":"2004","journal-title":"Semin. Immunol."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"927","DOI":"10.1016\/S0092-8674(02)01201-1","article-title":"Pattern recognition receptors: Doubling up for the innate immune response","volume":"111","author":"Gordon","year":"2002","journal-title":"Cell"},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1016\/S0167-5699(99)01547-9","article-title":"T-cell priming by type-1and type-2 polarized dendritic cells: The concept of a third signal","volume":"20","author":"Hilkens","year":"1999","journal-title":"Immunol. Today"},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1016\/j.bbrc.2006.05.135","article-title":"Bifunctional effects of fucoidan on the expression of inducible nitric oxide synthase","volume":"346","author":"Yang","year":"2006","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_143","doi-asserted-by":"crossref","unstructured":"Chen, L.M., Tseng, H.Y., Chen, Y.A., Al Haq, A.T., Hwang, P.A., and Hsu, H.L. (2020). Oligo-Fucoidan Prevents M2 Macrophage Differentiation and HCT116 Tumor Progression. Cancers, 12.","DOI":"10.3390\/cancers12020421"},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1016\/j.ijbiomac.2018.12.197","article-title":"In vitro and in vivo immunomodulatory effects of fucoidan compound agents","volume":"127","author":"Peng","year":"2019","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1038\/s41577-018-0061-z","article-title":"Natural killer cells and other innate lymphoid cells in cancer","volume":"18","author":"Chiossone","year":"2018","journal-title":"Nat. Rev. Immunol."},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1016\/j.ijbiomac.2017.11.102","article-title":"Effects of sulfated fucan from the sea cucumber Stichopus japonicus on natural killer cell activation and cytotoxicity","volume":"108","author":"Surayot","year":"2018","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"588","DOI":"10.1038\/s41419-022-05041-y","article-title":"Natural killer cell awakening: Unleash cancer-immunity cycle against glioblastoma","volume":"13","author":"Wang","year":"2022","journal-title":"Cell Death Dis."},{"key":"ref_148","doi-asserted-by":"crossref","unstructured":"Zhang, W., Okimura, T., Oda, T., and Jin, J.-O. (2019). Ascophyllan Induces Activation of Natural Killer Cells in Mice In Vivo and In Vitro. Mar. Drugs, 17.","DOI":"10.3390\/md17040197"},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1016\/j.ijbiomac.2022.03.122","article-title":"Comparison of the immune activation capacities of fucoidan and laminarin extracted from Laminaria japonica","volume":"208","author":"An","year":"2022","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"2337","DOI":"10.3390\/md10102337","article-title":"Effects of oral administration of fucoidan extracted from Cladosiphon okamuranus on tumor growth and survival time in a tumor-bearing mouse model","volume":"10","author":"Azuma","year":"2012","journal-title":"Mar. Drugs"},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"1116","DOI":"10.1177\/1535370216647123","article-title":"Emerging nanotechnologies for cancer immunotherapy","volume":"241","author":"Shukla","year":"2016","journal-title":"Exp. Biol. Med. (Maywood)"},{"key":"ref_152","doi-asserted-by":"crossref","unstructured":"Hwang, P.A., Lin, X.Z., Kuo, K.L., and Hsu, F.Y. (2017). Fabrication and Cytotoxicity of Fucoidan-Cisplatin Nanoparticles for Macrophage and Tumor Cells. Materials, 10.","DOI":"10.3390\/ma10030291"},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"120227","DOI":"10.1016\/j.biomaterials.2020.120227","article-title":"Fucoidan-based, tumor-activated nanoplatform for overcoming hypoxia and enhancing photodynamic therapy and antitumor immunity","volume":"257","author":"Chung","year":"2020","journal-title":"Biomaterials"},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"e10362","DOI":"10.1002\/btm2.10362","article-title":"Enhancing adoptive T-cell therapy with fucoidan-based IL-2 delivery microcapsules","volume":"8","author":"Jeon","year":"2023","journal-title":"Bioeng. Transl. Med."},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1016\/bs.acc.2020.06.004","article-title":"Chapter Five\u2014Cytokines and the immune response in obesity-related disorders","volume":"Volume 101","author":"Makowski","year":"2021","journal-title":"Advances in Clinical Chemistry"},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1038\/s41392-021-00506-6","article-title":"Targeting macrophages in cancer immunotherapy","volume":"6","author":"Duan","year":"2021","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"1105","DOI":"10.1080\/21645515.2016.1276682","article-title":"Targeting iNOS to increase efficacy of immunotherapies","volume":"13","author":"Ekmekcioglu","year":"2017","journal-title":"Hum. Vaccin Immunother."},{"key":"ref_158","first-page":"251","article-title":"Anti-tumor activity of fucoidan is mediated by nitric oxide released from macrophages","volume":"40","author":"Takeda","year":"2012","journal-title":"Int. J. Oncol."},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"118353","DOI":"10.1016\/j.carbpol.2021.118353","article-title":"The activation effects of fucoidan from sea cucumber Stichopus chloronotus on RAW264.7 cells via TLR2\/4-NF-\u03baB pathway and its structure-activity relationship","volume":"270","author":"Jiang","year":"2021","journal-title":"Carbohydr. Polym."},{"key":"ref_160","doi-asserted-by":"crossref","unstructured":"Yu, L., Jin, Y., Song, M., Zhao, Y., and Zhang, H. (2022). When Natural Compounds Meet Nanotechnology: Nature-Inspired Nanomedicines for Cancer Immunotherapy. Pharmaceutics, 14.","DOI":"10.3390\/pharmaceutics14081589"},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"909","DOI":"10.1016\/j.semcancer.2022.02.016","article-title":"Cancer immunotherapy by immune checkpoint blockade and its advanced application using bio-nanomaterials","volume":"86","author":"Yadav","year":"2022","journal-title":"Semin. Cancer Biol."},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"103160","DOI":"10.1016\/j.critrevonc.2020.103160","article-title":"The application of nano-medicine to overcome the challenges related to immune checkpoint blockades in cancer immunotherapy: Recent advances and opportunities","volume":"157","author":"Sanaei","year":"2021","journal-title":"Crit. Rev. Oncol. Hematol."},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1038\/s41571-019-0308-z","article-title":"Improving cancer immunotherapy using nanomedicines: Progress, opportunities and challenges","volume":"17","author":"Martin","year":"2020","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"ref_164","doi-asserted-by":"crossref","unstructured":"Tsai, H.L., Tai, C.J., Huang, C.W., Chang, F.R., and Wang, J.Y. (2017). Efficacy of Low-Molecular-Weight Fucoidan as a Supplemental Therapy in Metastatic Colorectal Cancer Patients: A Double-Blind Randomized Controlled Trial. Mar. Drugs, 15.","DOI":"10.3390\/md15040122"},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"319","DOI":"10.3892\/ol.2011.254","article-title":"Fucoidan reduces the toxicities of chemotherapy for patients with unresectable advanced or recurrent colorectal cancer","volume":"2","author":"Ikeguchi","year":"2011","journal-title":"Oncol. Lett."},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"2167","DOI":"10.1080\/1028415X.2021.1926140","article-title":"Fucoxanthin has potential for therapeutic efficacy in neurodegenerative disorders by acting on multiple targets","volume":"25","author":"Yang","year":"2022","journal-title":"Nutr. Neurosci."}],"container-title":["Marine Drugs"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1660-3397\/21\/2\/128\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T18:37:04Z","timestamp":1760121424000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1660-3397\/21\/2\/128"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,2,15]]},"references-count":166,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2023,2]]}},"alternative-id":["md21020128"],"URL":"https:\/\/doi.org\/10.3390\/md21020128","relation":{},"ISSN":["1660-3397"],"issn-type":[{"value":"1660-3397","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,2,15]]}}}