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通过生色团缀合的上转换纳米探针实时活体肝毒性监测

Real-Time In Vivo Hepatotoxicity Monitoring through Chromophore-Conjugated Photon-Upconverting Nanoprobes.

机构信息

State Key Laboratory of Natural Medicines, School of Basic Medical Sciences and Clinical Pharmacy, China Pharmaceutical University, Nanjing, Jiangsu, 211198, China.

Singapore Bioimaging Consortium, Agency for Science, Technology and Research (A* STAR), 138667, Singapore, Singapore.

出版信息

Angew Chem Int Ed Engl. 2017 Apr 3;56(15):4165-4169. doi: 10.1002/anie.201612020. Epub 2017 Mar 15.

Abstract

Drug toxicity is a long-standing concern of modern medicine. A typical anti-pain/fever drug paracetamol often causes hepatotoxicity due to peroxynitrite ONOO . Conventional blood tests fail to offer real-time unambiguous visualization of such hepatotoxicity in vivo. Here we report a luminescent approach to evaluate acute hepatotoxicity in vivo by chromophore-conjugated upconversion nanoparticles. Upon injection, these nanoprobes mainly accumulate in the liver and the luminescence of nanoparticles remains suppressed owing to energy transfer to the chromophore. ONOO can readily bleach the chromophore and thus recover the luminescence, the presence of ONOO in the liver leads to fast restoring of the near-infrared emission. Taking advantages of the high tissue-penetration capability of near-infrared excitation/emission, these nanoprobes achieve real-time monitoring of hepatotoxicity in living animals, thereby providing a convenient screening strategy for assessing hepatotoxicity of synthetic drugs.

摘要

药物毒性是现代医学长期关注的问题。一种典型的止痛/退热药物对乙酰氨基酚(acetaminophen),由于过氧亚硝酸盐(ONOO-)的存在,常常导致肝毒性。传统的血液检测无法实时明确地观察到体内的这种肝毒性。在这里,我们报告了一种通过发色团偶联上转换纳米粒子来评估体内急性肝毒性的发光方法。注射后,这些纳米探针主要在肝脏中积累,由于能量转移到发色团,纳米粒子的发光仍然受到抑制。ONOO-可以轻易地漂白发色团,从而恢复发光,在肝脏中存在 ONOO-会导致近红外发射的快速恢复。利用近红外激发/发射的高组织穿透能力,这些纳米探针实现了对活体动物肝毒性的实时监测,从而为评估合成药物的肝毒性提供了一种方便的筛选策略。

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