School of Medical Technology, Beijing Institute of Technology, Beijing 100081, P. R. China.
State Key Laboratory of Medicinal Chemical Biology, Tianjin Key Laboratory of Biosensing and Molecular Recognition, Frontiers Science Center for New Organic Matter, Research Center for Analytical Sciences, College of Chemistry, Nankai University, Tianjin 300071, P. R. China.
J Am Chem Soc. 2024 Nov 20;146(46):31873-31884. doi: 10.1021/jacs.4c11072. Epub 2024 Nov 6.
Simultaneous detection of different biomarkers related to the spatiotemporally dynamic immune events is of particular importance for the accurate evaluation of antitumor immune effects. Here, we have developed an AND-gate logic dual resonance energy transfer nanoprobe (named DRET) for dynamic monitoring of programmed CD8 T cell activation and tumor cell apoptosis. Immunotherapy-induced granzyme B secretion from CD8 T cells and the subsequent caspase-3 release from apoptotic tumor cells individually activate one of the tiers of the "AND-gate" logic DRET. The resulting fluorescence recovery and magnetic resonance T1 enhancement can be used for precise immunomodulatory drug screening, early efficacy prediction, and immune stratification. Particularly, not only "Responders" can be distinguished from "Non-responders", but also "Acquired resistance" can be identified from "Maintain responders", providing a novel approach to put forward the accurate evaluation of antitumor immunity.
同时检测与时空动态免疫事件相关的不同生物标志物对于准确评估抗肿瘤免疫效果尤为重要。在这里，我们开发了一种与门逻辑双共振能量转移纳米探针（命名为 DRET），用于动态监测程序性 CD8 T 细胞激活和肿瘤细胞凋亡。免疫治疗诱导的 CD8 T 细胞中颗粒酶 B 的分泌和随后凋亡肿瘤细胞中 caspase-3 的释放分别激活“与门”逻辑 DRET 的一个层次。由此产生的荧光恢复和磁共振 T1 增强可用于精确的免疫调节药物筛选、早期疗效预测和免疫分层。特别地，不仅可以将“应答者”与“无应答者”区分开来，而且可以将“获得性耐药”与“维持应答者”区分开来，为提出准确的抗肿瘤免疫评估提供了一种新方法。
