Abstract Cells possess inherent advantages to facilitate targeted payload delivery. Current strategies to conjugate payload carriers to the surface of cells are either via covalent bonds that not only involve complicated synthetic process but also often impair cellular functions, or via biological ligand-receptor interactions that are only specific to particular types of cells. Herein, we report a facile, bioorthogonal supramolecular conjugation strategy to prepare targeted cell-hitchhiking delivery systems, mediated via artificial host–guest interactions between β-cyclodextrin and adamantane, respectively anchored (via insertion) on the surfaces of live cells and payload carriers. In a paw swelling inflammation mouse model, supramolecularly conjugated macrophage-carriers (either cell–cell or cell-nanoparticle systems) were efficiently delivered hand-in-hand to the swelling paw, driven by the inflammatory tropism of macrophage. Furthermore, in an acute lung inflammation model of mouse, supramolecular conjugation of peritoneal macrophage and quercetin-loaded liposomes significantly improved targeting efficiency of the liposomes, and effectively alleviated the lung inflammation through the anti-inflammatory and anti-oxidative effects of quercetin. The cell-friendly, facile, host–guest interactions mediated cellular conjugation may provide the very first general strategy for preparing various cell-hitchhiking delivery systems to meet the needs of diverse biomedical applications.

中文翻译：

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用于靶向搭便车药物递送的生物正交超分子细胞偶联

摘要 细胞具有促进靶向有效载荷传递的固有优势。目前将有效载荷载体结合到细胞表面的策略要么是通过共价键，这不仅涉及复杂的合成过程，而且通常会损害细胞功能，或者通过仅特定于特定类型细胞的生物配体 - 受体相互作用。在此，我们报告了一种简便的生物正交超分子缀合策略，以制备靶向细胞搭便车递送系统，通过分别锚定（通过插入）在活细胞和有效载荷载体表面上的 β-环糊精和金刚烷之间的人工宿主 - 客体相互作用介导。在爪肿胀炎症小鼠模型中，在巨噬细胞的炎症趋向性的驱动下，超分子结合的巨噬细胞载体（细胞-细胞或细胞-纳米颗粒系统）被有效地手拉手输送到肿胀的爪子。此外，在小鼠急性肺部炎症模型中，腹腔巨噬细胞与槲皮素脂质体的超分子结合显着提高了脂质体的靶向效率，并通过槲皮素的抗炎和抗氧化作用有效缓解肺部炎症。细胞友好、简便、宿主-客体相互作用介导的细胞偶联可能为制备各种细胞搭便车递送系统以满足不同生物医学应用的需求提供了第一个通用策略。在小鼠急性肺部炎症模型中，腹腔巨噬细胞与槲皮素脂质体的超分子偶联显着提高脂质体的靶向效率，并通过槲皮素的抗炎和抗氧化作用有效缓解肺部炎症。细胞友好、简便、宿主-客体相互作用介导的细胞偶联可能为制备各种细胞搭便车递送系统以满足不同生物医学应用的需求提供了第一个通用策略。在小鼠急性肺部炎症模型中，腹腔巨噬细胞与槲皮素脂质体的超分子偶联显着提高脂质体的靶向效率，并通过槲皮素的抗炎和抗氧化作用有效缓解肺部炎症。细胞友好、简便、宿主-客体相互作用介导的细胞偶联可能为制备各种细胞搭便车递送系统以满足不同生物医学应用的需求提供了第一个通用策略。