Table 3.

Examples of metal-based nanomaterials for cancer vaccine delivery.

Material	Morphology	Immunogen	Results	Ref.
Aluminum hydroxide	Nanospheres (modified with polyethylenimine)	Ovalbumin	▪Easily internalized into DCs, ensuring antigen release into their cytoplasm ▪Significantly inhibited tumor growth ▪Considerably increased cytokine IL-12 secretion and expression of surface molecules CD80 and CD86 ▪Promoted the activation of tumor-associated T cells	[148]
Iron oxide	Nanospheres	Ovalbumin	▪Considerably promoted activation of immune cells ▪Significantly increased cytokine production ▪Induced potent humoral and cellular immune responses	[149]
Iron oxide	Nanospheres (coated with a lipid bilayer)	Endogenous tumor antigens (ETAs)	▪Able to capture ETAs from tumors and transport them to lymph nodes ▪In combination with anti-PD-L1 checkpoint blockade could eliminate primary tumors, suppress distant tumors, inhibit metastasis, and prolong the survival of model animals	[150]
Zinc oxide	Mesoporous nanocapsules	Ovalbumin	▪Enhanced expression of antigen-specific T-cells ▪Induced IFN-γ producing effector CD4+ and CD8+ T-cells ▪Increased antigen-specific IgG levels	[151]
Zinc oxide	Radially grown nanowires on poly-L-lactide microfibers	Carcinoembryonic antigen	▪Mild cellular toxicity ▪Effective delivery to DCs, stimulating them to express inflammatory cytokines and activation surface markers ▪Induced tumor antigen-specific cellular immunity ▪Significantly inhibited tumor growth ▪Reduced immune suppressive TReg cells ▪Enhanced the infiltration of T cells into tumor tissues	[152]
Magnesium-aluminum-layered double hydroxide	Nanospheres	Tyrosinase-related protein 2	▪Induced strong cytotoxic T-lymphocyte responses ▪Significantly inhibited melanoma tumor growth ▪The NPs allow loading of multi-antigens and immune stimulants, being promising for developing personalized therapeutic cancer vaccines	[153]
Calcium phosphate	Nanospheres (functionalized with lipids)	p-AH1-A5 peptide antigen	▪Reduced primary colon cancer growth rate ▪Arrested liver metastasis ▪Boosted the adaptive CD8+ T-cell population, without inciting increased populations of immune suppressive cell types (e.g., T-regulatory cells and myeloid derived suppressor cells)	[154]