Synthesis of NQO1-activatable Optoacoustic Probe and Its Imaging of Breast Cancer
Received date: 2020-10-06
Online published: 2020-11-17
Supported by
National Natural Science Foundation of China(21875069); Fund of Guangdong Provincial Key Laboratory of Luminescence from Molecular Aggregates(2019B030301003); and the Natural Science Foundation of Guangdong Province(2016A030312002)
NAD(P)H:quinone oxidoreductase-1 (NQO1) is a cytosolic two-electron-specific reductase whose abnormal expression is associated with breast cancer, and NQO1 has been regarded as an important biomarker for monitoring the occurrence and development of breast tumors. Although there are some research reports involving fluorescent probes for imaging NQO1 in vivo, they generally suffer from the strong light scattering by tissues which would cause the spatial resolution of fluorescent signals degrade rapidly with imaging depth. On the other hand, as an emerging detection and imaging modality, optoacoustic tomography (OAT) is capable of providing more detailed information in deep biological tissues than fluorescent imaging, since in OAT ultrasound signals are the reporting signals. To overcome the inherent defects of fluorescent imaging, in this work, we developed a novel near-infrared (NIR) NQO1-activatable optoacoustic (OA) probe TPA-X-Q based on the push-pull internal charge transfer (ICT) scaffold. TPA-X-Q consists of a NQO1-responsive moiety, quinone propionate group and a NIR chromophore TPA-X-OH. In the absence of the enzyme NQO1, the probe displays nearly no noticeable OA signal upon NIR excitation. Whereas in the presence of NQO1, the quinone propionate group of TPA-X-Q is reduced and cleaved by the enzymatic reaction triggered by NQO1, and thus TPA-X-Q is transformed into TPA-X-OH, consequently evident OA signal is generated, thereby realizing the detection and imaging of NQO1. As for the probe, the limit of detection (LOD) is determined to be 0.193 μg·mL –1. Furthermore, the probe TPA-X-Q displays several advantages, such as quite good selectivity towards NQO1, low cytotoxicity and excellent photostability. Moreover, the probe has been successfully utilized to detect and image the overexpressed NQO1 in the breast cancer-bearing mouse model. Orthogonal-view three-dimensional (3D) images can also be obtained by using multispectral optoacoustic tomography (MSOT), and thus precise localization of the breast cancer tumors can be achieved. This probe holds great potential for being employed as an efficacious tool for diagnosing breast cancer via responding to NQO1.
Key words： NQO1; optoacoustic probe; near-infrared; breast cancer; MSOT
Jing Huang , Chao Wang , Mingang Lin , Fang Zeng , Shuizhu Wu . Synthesis of NQO1-activatable Optoacoustic Probe and Its Imaging of Breast Cancer[J]. Acta Chimica Sinica, 2021 , 79(3) : 331 -337 . DOI: 10.6023/A20100459
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