Tandem post-synthetic modification of a zeolitic imidazolate framework for CXCR4-overexpressed esophageal squamous cell cancer imaging and therapy
Tandem post-synthetic modification of a zeolitic imidazolate framework for CXCR4-overexpressed esophageal squamous cell cancer imaging and therapy
复制标题
用于 CXCR4 过表达的食管鳞状细胞癌成像和治疗的沸石咪唑酯框架的串联合成后修饰
DOI：
10.1039/d0nr00895h
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发表时间：
2020-06-28
期刊：
影响因子：
6.7
通讯作者：
Wu, Aiguo
中科院分区：
文献类型：
--
作者：
Cao, Yi;Jiang, Zhenqi;Wu, Aiguo
沸石咪唑酯骨架（ZIF）作为新兴的多孔材料，因其前所未有的孔隙率和酸敏感降解而引起了人们的广泛关注，可实现高载药量和微环境响应的快速有效负载释放。然而，ZIF5的有限功能和缺点，例如早期药物释放、潜在的细胞毒性导致主要器官损伤，甚至导致动物死亡，阻碍了其进一步的生物医学应用。在这项工作中，我们报告了 ZIF-7 与金属离子和有机配体的首次串联合成后修饰。受与ZIF-7有机配体相似的苯并咪唑类抑制剂的启发，趋化因子（C-X-C基序）受体4（CXCR4）抑制剂AMD-070（AMD）和镁离子（Mn2+）成功串联交换至ZIF-7框架，形成了针对CXCR4过表达的食管鳞状细胞癌的主动靶向框架AMD-ZIF-7（Mn）。所得AMD-ZIF-7(Mn)在体外和体内均表现出良好的生物相容性。同时，它表现出优异的T-1加权磁共振成像性能和CXCR4靶向能力。负载5-Fu后，AMD-ZIF-7(Mn)/5-Fu对食管鳞状细胞癌的DNA损伤和CXCR4抑制表现出协同治疗作用。因此，我们提出了一种结构重建方法来有效探索和提高ZIF5在食管鳞状细胞癌治疗诊断中的生物医学应用。
Zeolitic imidazolate frameworks (ZIFs) as emerging porous materials have attracted remarkable attention for their unprecedented porosity and acidic sensitive degradation that enables high drug loading and microenvironment responsive fast payload release. However, the limited functions and disadvantages of ZIF5 such as early drug release, potential cytotoxicity inducing damage to major organs, and even death of animals, impede their further biomedical application. In this work, we report the first tandem post-synthetic modification of ZIF-7 with both metal ions and organic ligands. Inspired by the benzimidazole-like inhibitors that are similar to the organic ligand of ZIF-7, a chemokine (C-X-C motif) receptor 4 (CXCR4) inhibitor AMD-070 (AMD) and magnesium ions (Mn2+) were successfully tandem exchanged to the ZIF-7 framework, forming an active-targeting framework AMD-ZIF-7(Mn) for CXCR4-overexpressed esophageal squamous cell cancer. The obtained AMD-ZIF-7(Mn) showed good biocompatibility in vitro and in vivo. Meanwhile, it exhibited an excellent T-1-weighted magnetic resonance imaging performance and CXCR4 targeting ability. With 5-Fu loading, AMD-ZIF-7(Mn)/5-Fu showed a synergistic therapeutic effect in DNA damage and CXCR4 inhibition of esophageal squamous cell cancer. Therefore, we propose a structural reconstruction method to effectively explore and improve the biomedical application of ZIF5 in esophageal squamous cell cancer theranostics.