Bioorthogonal supramolecular cell-conjugation for targeted hitchhiking drug delivery
Bioorthogonal supramolecular cell-conjugation for targeted hitchhiking drug delivery
复制标题
用于靶向搭便车药物输送的生物正交超分子细胞缀合
DOI：
10.1016/j.mattod.2020.05.023
复制
发表时间：
2020-11-01
期刊：
影响因子：
24.2
通讯作者：
Wang, Ruibing
中科院分区：
文献类型：
--
作者：
Gao, Cheng;Cheng, Qian;Wang, Ruibing
细胞具有促进靶向有效载荷递送的固有优势。目前将有效载荷载体缀合至细胞表面的策略是通过共价键，其不仅涉及复杂的合成过程，而且经常损害细胞功能，或者通过仅特异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，生物正交的超分子缀合策略，以制备靶向细胞搭便车传递系统，通过β-环糊精和金刚烷之间的人工主客体相互作用介导，分别锚定（通过插入）在活细胞和有效载荷载体的表面上。在爪肿胀炎症小鼠模型中，超分子缀合的巨噬细胞-载体（细胞-细胞或细胞-纳米颗粒系统）通过巨噬细胞的炎性嗜性被有效地手拉手递送至肿胀爪。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偶联显著提高了脂质体的靶向性，并通过槲皮素的抗炎和抗氧化作用有效减轻了肺部炎症。细胞友好的，容易的，主-客体相互作用介导的细胞缀合可以提供用于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的第一个通用策略。
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 beta-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 antiinflammatory 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.