Laboratory of Chemical Biology and State Key Laboratory of Rare Earth Resource Utilization, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, Jilin, 130022, P. R. China.
University of Chinese Academy of Sciences, Beijing, 100039, P. R. China.
Angew Chem Int Ed Engl. 2021 Jul 5;60(28):15436-15444. doi: 10.1002/anie.202102286. Epub 2021 Jun 9.
Metabolic glycan labeling (MGL) followed by bioorthogonal chemistry provides a powerful tool for tumor imaging and therapy. However, selectively metabolic labeling of cells or tissues of interest remains a challenge. Particularly, owing to tumor heterogeneity including tumor subtypes and interpatient heterogeneity, it is far more difficult to realize tumor-cell-selective metabolic labeling for precise diagnosis. Inspired by nature, we designed azidosugar-functionalized metal-organic frameworks camouflaged with cancer cell membranes to accomplish cancer-cell-selective MGL in vivo. With abundant receptors, this biomimetic platform not only selectively targets homotypic cells but also realizes different breast cancer subtype-selective MGL. Moreover, the endo/lysosomal-escaped ZIF-8 can make azidosugar escape from lysosomes and accelerate its metabolic incorporation. This strategy also takes advantage of cancer-tissue-derived cell membranes, which may have huge potential for personalized diagnosis and therapy.
代谢糖基化标记 (MGL) 结合生物正交化学为肿瘤成像和治疗提供了强大的工具。然而，对感兴趣的细胞或组织进行选择性代谢标记仍然是一个挑战。特别是由于肿瘤异质性包括肿瘤亚型和个体间异质性，因此更难以实现肿瘤细胞选择性代谢标记以进行精确诊断。受自然启发，我们设计了带有叠氮糖功能化的金属-有机骨架，并用癌细胞膜伪装，以在体内实现肿瘤细胞选择性 MGL。由于有丰富的受体，这个仿生平台不仅可以选择性地靶向同型细胞，还可以实现不同乳腺癌亚型的选择性 MGL。此外，内体/溶酶体逃逸的 ZIF-8 可以使叠氮糖从溶酶体中逃逸，并加速其代谢掺入。该策略还利用了源自肿瘤组织的细胞膜，这对于个性化诊断和治疗可能具有巨大的潜力。
