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Figure 2. Schematic illustration of the metastatic cascade and nanomaterial-driven combinatorial immunotherapeutic strategies targeting organ-specific metastasis. This diagram depicts the multistep metastatic process including intravasation, dissemination, extravasation, and colonization at distant organs (lung, liver, bone, brain). Smart nanomaterials interrupt the metastatic cascade by remodeling the immunosuppressive TME, inhibiting ECM remodeling and CAF activity, blocking key oncogenic signaling pathways, and suppressing the formation of metastatic niches. Meanwhile, nanoplatforms trigger ICD, promote CTL infiltration, reduce Treg abundance, and reactivate systemic antitumor immune responses to inhibit tumor invasion and distant metastasis. CAF: Cancer-associated fibroblast; CTL: cytotoxic T-lymphocyte; ECM: extracellular matrix; ICD: immunogenic cell death; MMP: matrix metalloproteinase; MUC1: Mucin-1; OPG: osteoprotegerin; PTHrP: parathyroid hormone related protein; RANKL: receptor activator of nuclear factor-κB ligand; S1PR3: sphingosine-1-phosphate receptor 3; STC1: stanniocalcin 1; STING: stimulator of interferon gene; Treg: T regulatory cell; VEGF: vascular endothelial growth factor; TME: tumor microenvironment; ROS: reactive oxygen species; AI: artificial intelligence; STAT3: signal transducer and activator of transcription 3; CSF-1: colony-stimulating factor 1; NF-κB: nuclear factor kappa B; CCL5/7: chemokine ligand 5/7; VCAM1: vascular cell adhesion molecule-1; VLA-4: very late appearing antigen-4; SPARC: secreted protein acidic and rich in cysteine; CXCL8/12: C-X-C motif chemokine ligand 8/12; TGF-β: transforming growth factor beta; GDF15: growth differentiation factor 15; CCL2: chemokine ligand 2; PANKL: primary adrenal NK/T cell lymphoma; CXCR4: Chemokine receptor 4; IL-1β: interleukin-1 beta; IL-6: interleukin-6; TNF-α: tumor necrosis factor-α; GSH: glutathione. Drawn by Figdraw (ID: UPRTY104f0).