Supramolecular Macrophage-Liposome Marriage for Cell-Hitchhiking Delivery and Immunotherapy of Acute Pneumonia and Melanoma
Supramolecular Macrophage-Liposome Marriage for Cell-Hitchhiking Delivery and Immunotherapy of Acute Pneumonia and Melanoma
复制标题
超分子巨噬细胞-脂质体结合用于急性肺炎和黑色素瘤的细胞搭便车递送和免疫治疗
DOI：
10.1002/adfm.202102440
复制
发表时间：
2021-06-26
影响因子：
19
通讯作者：
Wang, Ruibing
中科院分区：
文献类型：
--
作者：
Gao, Cheng;Cheng, Qian;Wang, Ruibing
由于许多疾病都与炎症有关，免疫细胞的炎症取向可能会以高度靶向性的方式将细胞搭便车直接带到疾病组织中。目前的细胞搭便车策略要么依赖于细胞内化，要么依赖于共价表面结合，这往往会影响细胞运输的生理功能。因此，开发了一种细胞友好、主客体化学介导的巨噬细胞-脂质体结合物(M-L)，以实现极其稳定的细胞搭便车药物输送。M-L是通过简单的超分子“牵手”和葫芦巴[7]脲(CB[7])与金刚烷的结合而制备的，分别锚定在巨噬细胞和脂质体的表面，显示了在炎症肺中的靶向蓄积和对小鼠急性肺炎的有效治疗。在装载毒性化疗药物(如阿霉素和奥沙利铂)后，M-L将有效载荷携带到炎性癌症组织，并显著增强小鼠黑色素瘤的化学免疫治疗。基本上，这种基于CB[7]的超分子M-L共轭策略对巨噬细胞的迁移和侵袭行为的影响可以忽略不计。M-L治疗后小鼠炎症组织的体内病理分析进一步表明，巨噬细胞和脂质体携手递送。这种基于CB[7]的超分子细胞共轭策略潜在地解决了当前基于细胞的递送系统所面临的关键挑战。
As many diseases are related to inflammation, the inflammatory tropism of immune cells may bring cell-hitchhikers directly to the disease tissues in a highly targeted manner. The current cell-hitchhiking strategies rely on either cellular internalization or covalent surface conjugation, which often affects the physiological function of transporting cells. Herein, a cell-friendly, host-guest chemistry mediated macrophage-liposome conjugate (M-L) is developed for extremely stable cell-hitchhiking drug delivery. M-L is prepared via simple supramolecular "hand-holding" and marriage between cucurbit[7]uril (CB[7]) and adamantane, respectively anchored on the surface of the macrophage and liposome, which demonstrates targeted accumulation in the inflamed lung and effective therapy of acute pneumonia in mice when loaded with quercetin. Upon loading toxic chemotherapeutic agents (such as doxorubicin and oxaliplatin), M-L carries the payloads to the inflammatory cancer tissue and significantly enhances the chemoimmunotherapy of melanoma in mice. Fundamentally, this CB[7]-based supramolecular M-L conjugation strategy shows negligible effects on the migratory and invasive behaviors of macrophages. In vivo pathological analysis of the inflammatory tissues in mice after treatment with M-L further suggests that macrophage and liposomes are delivered together hand in hand. This CB[7]-based, supramolecular cell-conjugation strategy potentially addresses the key challenges faced by the current cell-based delivery systems.