Zhu Zhirong, Liu Shichang, Wu Xupeng, Yu Qianqian, Duan Yi, Hu Shanshan, Zhu Wei-Hong, Wang Qi
School of Chemistry and Molecular Engineering Shanghai Key Laboratory of Functional Materials Chemistry Key Laboratory for Advanced Materials and Institute of Fine Chemicals Joint International Research Laboratory of Precision Chemistry and Molecular Engineering Feringa Nobel Prize Scientist Joint Research Center Frontiers Science Center for Materiobiology and Dynamic Chemistry East China University of Science and Technology Shanghai China.
School of Biomedical Engineering State Key Laboratory of Oncogenes and Related Genes Renji Hospital Shanghai Jiao Tong University Shanghai China.
Smart Mol. 2024 Sep 4;3(2):e20240028. doi: 10.1002/smo.20240028. eCollection 2025 Jun.
The development of efficient aggregation-induced emission (AIE) active probes is crucial for disease diagnosis, particularly for tumors and cardiovascular diseases. Current AIE-active probes primarily focus on improving their water solubility to resist aggregation, thereby achieving an initial fluorescence-off state. However, the complex biological environment can cause undesirable aggregation, resulting in false signals. To address this issue, we have ingeniously introduced an azo group into the AIE luminogen (AIEgen), developing a reductase-activated AIE probe, Azo-quinoline-malononitrile (QM)-PN, for imaging hypoxic environments. In this probe, the azo group promotes intramolecular motion through rapid / isomerization, causing the excited state energy to dissipate via non-radiative decay, thus turning off the initial fluorescence. In the presence of reductase, Azo-QM-PN is reduced and cleaved to produce the hydrophobic AIEgen NH-QM-PN, which subsequently aggregates and generates an in situ AIE signal, thereby imaging the hypoxic environment with reductase. Encapsulation of Azo-QM-PN with DSPE-PEG results in the formation of the nanoprobe Azo-QM-PN NPs, which can effectively penetrate cell membranes, specifically illuminate tumor cells, monitor fluctuations in azo reductase levels, and deeply penetrate and image multicellular tumor spheroids, demonstrating potential for hypoxic tumor imaging. Additionally, the nanoprobe Azo-QM-PN NPs can selectively image hypoxic atherosclerotic plaque tissues, showing potential for detecting atherosclerosis. Therefore, in this study, we successfully developed an enzyme-activated AIE probe for imaging hypoxic environments, laying the foundation for further clinical applications.
高效聚集诱导发光（AIE）活性探针的开发对于疾病诊断至关重要，尤其是对于肿瘤和心血管疾病。当前的AIE活性探针主要致力于提高其水溶性以抵抗聚集，从而实现初始荧光关闭状态。然而，复杂的生物环境可能导致不良聚集，产生假信号。为了解决这个问题，我们巧妙地将一个偶氮基团引入AIE发光体（AIEgen）中，开发了一种用于低氧环境成像的还原酶激活AIE探针，即偶氮喹啉-丙二腈（QM）-PN。在该探针中，偶氮基团通过快速顺反异构化促进分子内运动，使激发态能量通过非辐射衰变耗散，从而关闭初始荧光。在还原酶存在的情况下，Azo-QM-PN被还原并裂解产生疏水性AIEgen NH-QM-PN，随后其聚集并产生原位AIE信号，从而利用还原酶对低氧环境进行成像。用DSPE-PEG包裹Azo-QM-PN可形成纳米探针Azo-QM-PN NPs，其能够有效穿透细胞膜，特异性照亮肿瘤细胞，监测偶氮还原酶水平的波动，并深入穿透多细胞肿瘤球体并成像，显示出低氧肿瘤成像的潜力。此外，纳米探针Azo-QM-PN NPs能够选择性地对低氧动脉粥样硬化斑块组织进行成像，显示出检测动脉粥样硬化的潜力。因此，在本研究中，我们成功开发了一种用于低氧环境成像的酶激活AIE探针，为进一步的临床应用奠定了基础。
