A Nitroreductase-Activatable Metabolic Reporter for Covalent Labeling of Pathological Hypoxic Cells in Tumorigenesis

Zhimin Wang*, Jun Wei Lau, Songhan Liu, Ziheng Ren, Zhiyuan Gong, Xiaogang Liu, Bengang Xing*

*此作品的通讯作者

科研成果: 期刊稿件文章同行评审

1 引用 (Scopus)

摘要

Aberrant hypoxic stress will initiate a cascade of pathological consequence observed prominently in tumorigenesis. Understanding of hypoxia's role in tumorigenesis is highly essential for developing effective therapeutics, which necessitates reliable tools to specifically distinguish hypoxic tumor cells (or tissues) and correlate their dynamics with the status of disease in complex living settings for precise theranostics. So far, disparate hypoxia-responsive probe molecules and prodrugs were designed via chemical or enzymatic reactions, yet their capability in real-time reporting pathogenesis development is often compromised due to unrestricted diffusion and less selectivity towards the environmental responsiveness. Herein we present an oxygen-insensitive nitroreductase (NTR)-activatable glycan metabolic reporter (pNB-ManNAz) capable of covalently labeling hypoxic tumor cells and tissues. Under pathophysiological hypoxic environments, the caged non-metabolizable precursor pNB-ManNAz exhibited unique responsiveness to cellular NTR, culminating in structural self-immolation and the resultant ManNAz could incorporate onto cell surface glycoproteins, thereby facilitating fluorescence labeling via bioorthogonal chemistry. This NTR-responsive metabolic reporter demonstrated broad applicability for multicellular hypoxia labeling, particularly in the dynamic monitoring of orthotopic tumorigenesis and targeted tumor phototherapy in vivo. We anticipate that this approach holds promise for investigating hypoxia-related pathological progression, offering valuable insights for accurate diagnosis and treatment.

源语言英语
文章编号e202411636
期刊Angewandte Chemie - International Edition
63
51
DOI
出版状态已出版 - 16 12月 2024

指纹

探究 'A Nitroreductase-Activatable Metabolic Reporter for Covalent Labeling of Pathological Hypoxic Cells in Tumorigenesis' 的科研主题。它们共同构成独一无二的指纹。

引用此