Department of Radiology, Tongji Hospital, School of Medicine, Tongji University, Shanghai, 200065, P. R. China.
Institute for Translational Medicine, Shanghai East Hospital, Institute for biomedical Engineering and Nanoscience, School of Medicine, Tongji University, Shanghai, 200092, P. R. China.
Adv Healthc Mater. 2023 Sep;12(24):e2300602. doi: 10.1002/adhm.202300602. Epub 2023 May 25.
Accurately evaluating tumor responses to immunotherapy is clinically relevant. However, non-invasive, real-time visualization techniques to evaluate tumor immunotherapy are still lacking. Herein, a smart responsive fluorescence-MR dual-modal nanoprobe, QM(GP)-MZF(CP), is reported that can be targeted for cleavage by the cytotoxic T cell activation marker granzyme B and the apoptosis-related marker cysteine-aspartic acid-specific protease 3 (Caspase-3). The probe uses quinoline-malononitrile (QM), an aggregation-induced emission luminogen, and Mn-Zn ferrite magnetic nanoparticles (MZF-MNPs), a T2-weighted imaging (T2WI) contrast agent, as imaging molecules that are linked with the substrate peptides specific to granzyme B and Caspase-3. Therefore, both granzyme B and Caspase-3 can target and cleave the substrate peptides in QM(GP)-MZF(CP). Via aggregation-induced fluorescence imaging of QM and the aggregation-induced T2WI-enhanced imaging effect of MZF-MNPs, the status of T cells after tumor immunotherapy and the subsequent triggering of tumor cell apoptosis can be determined to identify tumor responsiveness to immunotherapy and thereby evaluate the effectiveness of this therapy in the early stages of treatment.
准确评估肿瘤对免疫治疗的反应具有临床相关性。然而，目前仍缺乏用于评估肿瘤免疫治疗的非侵入性、实时可视化技术。在此，我们报道了一种智能响应荧光-MR 双模纳米探针 QM(GP)-MZF(CP)，它可以被细胞毒性 T 细胞激活标志物颗粒酶 B 和凋亡相关标志物半胱氨酸天冬氨酸特异性蛋白酶 3 (Caspase-3) 靶向切割。该探针使用具有聚集诱导发光特性的喹啉-马来二腈 (QM) 和锰锌铁氧体磁性纳米粒子 (MZF-MNPs) 作为 T2 加权成像 (T2WI) 造影剂的成像分子，与颗粒酶 B 和 Caspase-3 的特异性底物肽相连。因此，颗粒酶 B 和 Caspase-3 都可以靶向和切割 QM(GP)-MZF(CP)中的底物肽。通过 QM 的聚集诱导荧光成像和 MZF-MNPs 的聚集诱导 T2WI 增强成像效应，可以确定肿瘤免疫治疗后 T 细胞的状态以及随后肿瘤细胞的凋亡触发情况，从而确定肿瘤对免疫治疗的反应性，从而在治疗早期评估该治疗的有效性。
