Acta Chimica Sinica ›› 2021, Vol. 79 ›› Issue (3): 331-337.DOI: 10.6023/A20100459 Previous Articles     Next Articles



黄靖1, 王超1, 林敏刚1, 曾钫1,*(), 吴水珠1,*()   

  1. 1 华南理工大学发光材料与器件国家重点实验室 广东省分子聚集发光重点实验室 华南理工大学材料科学与工程学院 广州 510640
  • 投稿日期:2020-10-06 发布日期:2020-11-17
  • 通讯作者: 曾钫, 吴水珠
  • 作者简介:
    * E-mail: ; Tel.: 020-22236262; Fax: 020-22236363
    † 作者贡献相同.
  • 基金资助:
    项目受国家自然科学基金(21875069); 广东省分子聚集发光重点实验室课题(2019B030301003); 广东省自然科学基金(2016A030312002)

Synthesis of NQO1-activatable Optoacoustic Probe and Its Imaging of Breast Cancer

Jing Huang1, Chao Wang1, Mingang Lin1, Fang Zeng1,*(), Shuizhu Wu1,*()   

  1. 1 South China University of Technology, State Key Laboratory of Luminescent Materials & Devices, College of Materials Science and Engineering, GuangZhou 510640, China
  • Received:2020-10-06 Published:2020-11-17
  • Contact: Fang Zeng, Shuizhu Wu
  • 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