MOE key laboratory for analytical science of food safety and biology Institution, College of Chemistry, Fuzhou University, Fuzhou 350108, China.
Department of Radiation Oncology, Fujian Medical University Cancer Hospital, Fujian Cancer Hospital, Fuzhou 350014, China.
Anal Chem. 2022 Mar 29;94(12):5204-5211. doi: 10.1021/acs.analchem.2c00340. Epub 2022 Mar 21.
Owing to the high sensitivity and high spatial resolution, fluorescence (FL) imaging has been widely applied for visualizing biological processes. To gain insight into molecular events on deeper tissues, photoacoustic (PA) imaging with better deep-tissue imaging capability can be incorporated to provide complementary visualization and quantitative information on the pathological status. However, the development of activatable imaging probes to achieve both FL and PA signal amplification remains challenging because the enhancement of light absorption in PA imaging often caused the quenching of FL signal. Herein, we first developed a caspase-3 enzyme activatable nanoprobe of a nanogapped gold nanoparticle coated with AIE molecule INT20 and DEVD peptides (AuNNP@DEVD-INT20) for tumor FL and PA imaging and subsequent imaging-guided radiotherapy. The nanoprobe could interact with GSH and caspase-3 enzyme to liberate INT20 molecules, leading to AIE. Simultaneously, the self-assembly of AuNPs was achieved through the cross-linking reaction between the sulfhydryl and the maleimide, resulting in ratiometric PA imaging in tumor. Remarkably, the nanoprobe can generate richful ROS for cancer radiotherapy under X-ray irradiation. The platform not only achieves the aggregation-induced FL and PA signal enhancement but also provides a general strategy for imaging of various biomarkers, eventually benefiting precise cancer therapy.
由于具有高灵敏度和高空间分辨率，荧光（FL）成像已被广泛应用于可视化生物过程。为了深入了解深层组织中的分子事件，可以结合具有更好的深层组织成像能力的光声（PA）成像，提供有关病理状态的互补可视化和定量信息。然而，开发可激活的成像探针以实现 FL 和 PA 信号放大仍然具有挑战性，因为 PA 成像中光吸收的增强常常导致 FL 信号的猝灭。在此，我们首次开发了一种 caspase-3 酶激活的纳米探针，该探针由涂有 AIE 分子 INT20 和 DEVD 肽的纳米间隙金纳米颗粒（AuNNP@DEVD-INT20）组成，用于肿瘤 FL 和 PA 成像以及随后的成像引导的放射治疗。该纳米探针可以与 GSH 和 caspase-3 酶相互作用，释放出 INT20 分子，从而产生 AIE。同时，通过巯基和马来酰亚胺之间的交联反应实现了 AuNPs 的自组装，从而在肿瘤中实现了比率型 PA 成像。值得注意的是，该纳米探针在 X 射线照射下可产生丰富的 ROS 用于癌症放射治疗。该平台不仅实现了聚集诱导的 FL 和 PA 信号增强，而且为各种生物标志物的成像提供了一种通用策略，最终有益于精确的癌症治疗。
