Supramolecular Biomimetic Topology: Macrophage-Engaged Neoadjuvant Platform for Preoperative Immunotherapy

The persistent immunosuppression and spatial heterogeneity of advanced solid tumors necessitate next-generation neoadjuvant platforms capable of reprogramming tumor microenvironments while overcoming resistance to immune checkpoint blockade. Addressing this unmet clinical challenge, we report a β-glucan-empowered nano-neoadjuvant agents (NNAs) engineered through topology-guided supramolecular assembly of pathogen-mimetic β-glucan motifs onto photoresponsive single-wall carbon nanotubes. This biomimetic architecture capitalizes on three synergistic mechanisms: (1) Dectin-1-mediated pathogen-associated molecular pattern recognition to rewire myeloid cell functionality, (2) endogenous leukocyte-hitchhiking delivery paradigm, and (3) spatiotemporally controlled photothermal ablation via near-infrared transducing SWNT cores. NNAs also orchestrates a proinflammatory cascade involving IL-12-dependent Th1 polarization and activation, effectively converting “cold” tumors into immunogenic niches. This strategy redefines preoperative therapeutic paradigms, offering a multimodal platform to harness the proinflammatory adjuvant effect of SWNTs for preoperative immunomodulation in advanced-stage malignancies. By bridging innate immune recognition with nanotechnology-enabled precision, this paradigm establishes a new roadmap for preoperative conditioning of advanced malignancies, offering a theranostic framework to transform surgical outcomes through immunologically informed nanomedicine design.