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bioRxiv · 10.1101/2025.03.02.641066

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

Wu, H.·Zhong, D.·Gu, Z.
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Abstract

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 {beta}-glucan-empowered nano-neoadjuvant agents (NNAs) engineered through topology-guided supramolecular assembly of pathogen-mimetic {beta}-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.

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Wu, H., Zhong, D., Gu, Z.. 2025-03-10. Supramolecular Biomimetic Topology: Macrophage-Engaged Neoadjuvant Platform for Preoperative Immunotherapy. https://doi.org/10.1101/2025.03.02.641066

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