Table 3.

Fucoidans in novel dosage form enhance immunotherapy efficacy.

Source of Fucoidan	Brief Description	Dosage Forms	Effects of Fucoidan	Ref.
Fucus vesiculosus	Combined fucoidan-based magnetic nanoparticles and immunomodulators enhance tumor-localized immunotherapy.	Nanoparticles (fucoidan-containing formulations: IO@FuDex1, IO@FuDex2, IO@FuDex3, M-IO@ FuDex1, M-IO@ FuDex3, and M-IO@ FuDex3)	IO@Fu${\mathrm{Dex}}^2$-H: improved targeting efficiency; IO@Fu${\mathrm{Dex}}^2$ and IO@Fu${\mathrm{Dex}}^3$: increased the cell association via a slow elevation of median fluorescence index (MFI) in 4T1 cells; IO@Fu${\mathrm{Dex}}^3$-H: significantly increased the MFI in $\mathrm{CD}{8}^{+}$T cells; targeted PD-L1 receptors and associated with 4T1 cells; inhibited lung metastasis in 4T1 cancer model; M-IOFuDex (magnetic navigation): enhanced tumor selectivity; increased T cell proliferation; decreased Tregs and TAMs in TME; IO@FuDex and IO@Fu${\mathrm{Dex}}^3$: inhibited the CT-26 tumor cell growth and extended the median survival to 62 days; reduced spleen Tregs; IO@Fu${\mathrm{Dex}}^3$ and M-IO@Fu${\mathrm{Dex}}^3$ increased TNF-$\alpha$, VEGF, and TGF-$\beta ;$ IO@Fu${\mathrm{Dex}}^1$, IO@Fu${\mathrm{Dex}}^2$, IO@Fu${\mathrm{Dex}}^3$, and M-IO@Fu${\mathrm{Dex}}^3: \uparrow$ antitumoral effects and median survival.	[126]
Fucus vesiculosus	Enhanced adoptive T cell therapy using fucoidan-based IL-2 delivery microcapsules.	Microcapsules (fucoidan-based coacervate-laden injectable hydrogel (${\mathrm{FPC}}^2-\mathrm{IG}$))	Acted as an IL-2 delivery vehicle for enhancing adoptive T cell therapy (ACT); increased tumor-infiltrating $\mathrm{CD}{8}^{+}$ T cells in CT26-bearing mice with ${\mathrm{FPC}}^2-\mathrm{IG}-\mathrm{IL}-2$ injection than ${\mathrm{FPC}}^2-\mathrm{IG}$ injection; Downregulated CD62L and enriched ${\mathrm{T}}_{\mathrm{EM}}$ and ${\mathrm{T}}_{\mathrm{EFF}}$ cell generation; promoted STAT5 phosphorylation in $\mathrm{CD}{8}^{+}$ T cells; increased Treg, NK, DNT, NKT, B, $\mathrm{CD}{8}^{+}$, and $\mathrm{CD}{4}^{+}$ T cell populations; induced a higher Ki-67 expression in CT26-bearing mice; combination therapy (anti-PD-1 + ${\mathrm{FPC}}^2-\mathrm{IG}-\mathrm{IL}-2$) reduced CT26 tumor cell growth and increased the IFN-$\gamma$ levels in tumor-infiltrating $\mathrm{CD}{8}^{+}$T cells; increased naïve OT-I T and NY-ESO-1 TCR- T cell proliferation; decreased the expression of PD-1, Tim-3, TIGIT, and LAG-3 in tumor-infiltrating NY-ESO-1 TCR T cells.	[154]
Fucus vesiculosus	Cytotoxicity and fabrication of fucoidan-cisplatin nanoparticles for macrophage and tumor cells.	Nanoparticles	Increased the cell viability of RAW264.7 macrophages; non-cytotoxic to RAW264.7 macrophages; reduced the cytotoxicity of cisplatin; inhibited HCT-8 cell growth.	[152]
Laminaria japonica	Fucoidan-based and tumor-activated nanoplatform overcame hypoxia and enhanced photodynamic therapy and antitumor immunity.	Nanoparticles	Significantly increased the VP fluorescent emission in FM@VP-treated MDA-MB-231 cells; MDA-MB-231 cells took up greater FM@VP nanoparticle clusters; inhibited MDA-MB-231 and MDA-MB-468 cell growth; decreased TNBC cell viability, upregulated P-selectin level; overcome tumor hypoxia; decreased pro-angiogenesis generated by hypoxic tumor-elicited pro-angiogenesis; inhibited YAP levels, CTGF, cyclin D1, and EGFR in MDA-MB-231 cells; attenuated the Hippo signaling; downregulated the protein levels of PD-L1; enhanced T cell-mediated cytotoxicity; suppressed orthotopic 4T1 tumor cells growth and metastatic colonization of lung tumor; downregulated Treg cell infiltration; increased the expressions of granzyme B and IFN-$\gamma$; increased CD4 and CD8 T cells but decreased TAMs.	[153]
Cladosiphon okamuranus	Immunomodulatory effects of fucoidan in mice.	Oral gavage	Increased the proliferation of splenocytes that activated by concanavalin A and LPS, and increased macrophage phagocytosis activity and the levels of IL-2, IFN-$\gamma \mathrm{and}$ serum IgM; decreased the levels of IL-4, IL-5 and serum IgE.	[2]
Fucus vesiculosus, Ascophyllu nodosum	Fucoidan-supplemented diet coordinated with ICBs to potentiate its antitumor immunity	Oral	Enhanced the therapeutic efficacy of PD-1 blockade; reduced B16 melanoma cell growth, volumes, and weights. Increased the proliferation of $\mathrm{CD}{8}^{+}$T, NK, and tumor-infiltrating T cells; activated DC maturation; increased the proliferation of $\mathrm{CD}{8}^{+}$T cells via increasing the production of IFN-$\gamma$ and TNF-$\alpha ;$ activated $\mathrm{CD}{8}^{+}$T cells through the JAK/STAT pathway.	[18]