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NQO-1 酶激活的近红外诊疗剂用于胰腺癌。

NQO-1 Enzyme-Activated NIR Theranostic Agent for Pancreatic Cancer.

机构信息

School of Ophthalmology & Optometry, School of Biomedical Engineering, Wenzhou Medical University, Wenzhou 325035, China.

Wenzhou Institute, University of Chinese Academy of Sciences, Wenzhou 325000, China.

出版信息

Anal Chem. 2022 Aug 16;94(32):11159-11167. doi: 10.1021/acs.analchem.2c01189. Epub 2022 Aug 2.

Abstract

Pancreatic cancer (PC) is one of the most lethal cancers worldwide, which is usually diagnosed in the advanced stage and is highly resistant to traditional chemotherapy, radiotherapy, and immunotherapy. Therefore, there is an urgent need for developing new PC-specific imaging and treatment. In this study, an quinone oxidoreductase 1 (NQO-1)-activated near-infrared (NIR) agent, , was synthesized. is almost nonemissive, while its NIR emission at 705 nm is triggered by NQO-1-induced reduction in the PC cells. In addition, the reduction product, , is specifically enriched in mitochondria and lysosomes and acts as an effective chemotherapeutic agent to selectively induce pancreatic cancer cell death the cell pyroptosis pathway. Further studies have shown that is suitable for imaging of clinical PC sections and solid tumors from patients. We expect this study will be helpful in the future for the design of targeted theranostic agents for PC.

摘要

胰腺癌(PC)是全球最致命的癌症之一,通常在晚期诊断,并且对传统的化疗、放疗和免疫疗法具有高度抗性。因此,迫切需要开发新的 PC 特异性成像和治疗方法。在本研究中,合成了一种醌氧化还原酶 1(NQO-1)激活的近红外(NIR)试剂 。 几乎不发荧光,而其在 705nm 处的 NIR 发射则由 NQO-1 诱导的 PC 细胞还原触发。此外,还原产物 ,特异性地在溶酶体和线粒体中富集,并作为有效的化学治疗剂,通过细胞焦亡途径选择性诱导胰腺癌细胞死亡。进一步的研究表明, 适合对临床 PC 切片和来自患者的实体瘤进行成像。我们期望这项研究将有助于未来设计针对 PC 的靶向治疗药物。

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