Frontiers Science Center for Transformative Molecules, School of Chemistry and Chemical Engineering, School of Biomedical Engineering, National Center for Translational Medicine, Zhangjiang Institute for Advanced Study, Shanghai Jiao Tong University, Shanghai, China.
Songjiang Hospital and Songjiang Research Institute, Shanghai Key Laboratory of Emotions and Affective Disorders, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Nat Nanotechnol. 2024 Nov;19(11):1712-1722. doi: 10.1038/s41565-024-01733-y. Epub 2024 Aug 5.
Metabolic dysregulation constitutes a pivotal feature of cancer progression. Enzymes with multiple metal active sites play a major role in this process. Here we report the first metabolic-enzyme-like FeMoO nanocatalyst, dubbed 'artificial metabzyme'. It showcases dual active centres, namely, Fe and tetrahedral Mo, that mirror the characteristic architecture of the archetypal metabolic enzyme xanthine oxidoreductase. Employing spatially dynamic metabolomics in conjunction with the assessments of tumour-associated metabolites, we demonstrate that FeMoO metabzyme catalyses the metabolic conversion of tumour-abundant xanthine into uric acid. Subsequent metabolic adjustments orchestrate crosstalk with immune cells, suggesting a potential therapeutic pathway for cancer. Our study introduces an innovative paradigm in cancer therapy, where tumour cells are metabolically reprogrammed to autonomously modulate and directly interface with immune cells through the intervention of an artificial metabzyme, for tumour-cell-specific metabolic therapy.
代谢失调是癌症进展的一个关键特征。具有多个金属活性位点的酶在这个过程中起着主要作用。在这里，我们报告了第一个代谢酶样的 FeMoO 纳米催化剂，称为“人工代谢酶”。它展示了两个活性中心，即 Fe 和四面体 Mo，它们反映了典型代谢酶黄嘌呤氧化还原酶的特征结构。我们采用空间动态代谢组学，并结合对肿瘤相关代谢物的评估，证明了 FeMoO 代谢酶能够催化肿瘤中丰富的黄嘌呤转化为尿酸。随后的代谢调整与免疫细胞相互作用，为癌症提供了一种潜在的治疗途径。我们的研究为癌症治疗引入了一个创新的范例，其中肿瘤细胞通过代谢重编程，通过人工代谢酶的干预，自主调节并直接与免疫细胞相互作用，实现肿瘤细胞特异性的代谢治疗。
