Ma Bailing, Lu Mi, Yu Bo-Yang, Tian Jiangwei
State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of TCM Evaluation and Translational Research, School of Traditional Chinese Pharmacy, China Pharmaceutical University Nanjing 211198 P. R. China
RSC Adv. 2018 Jun 15;8(39):22062-22068. doi: 10.1039/c8ra01424h. eCollection 2018 Jun 13.
Drug-induced liver injury (DILI) is a serious concern in modern medicine due to its unpredictability. Currently, biochemical serum markers are being used in DILI detection. However, these biomarker-based methods lack sensitivity and specificity. A high intracellular level of hydroxyl radicals (˙OH) has been regarded as an early indicator of DILI. Therefore, we proposed an ˙OH-responsive and hepatocyte-targeted nanoprobe conjugation of carboxyfluorescein-labeled DNA and pegylated galactose on the surface of gold nanoparticles. The nanoprobe could bind to a hepatocyte-specific asialoglycoprotein receptor through galactose, and it could be internalized into liver cells. In the presence of high levels of ˙OH in DILI, the DNA could be cleaved to release carboxyfluorescein, leading to remarkable fluorescence enhancement for ˙OH detection. Confocal fluorescence imaging demonstrated that the nanoprobe could be successfully applied in monitoring high ˙OH levels resulting from acetaminophen or triptolide-induced liver injury, which may provide a simple but powerful protocol for the prediction of DILI.
药物性肝损伤（DILI）因其不可预测性而成为现代医学中一个严重问题。目前，生化血清标志物被用于DILI检测。然而，这些基于生物标志物的方法缺乏敏感性和特异性。细胞内高水平的羟基自由基（˙OH）被视为DILI的早期指标。因此，我们提出了一种˙OH响应性且靶向肝细胞的纳米探针，它是通过将羧基荧光素标记的DNA与聚乙二醇化半乳糖共轭到金纳米颗粒表面而构建的。该纳米探针可通过半乳糖与肝细胞特异性去唾液酸糖蛋白受体结合，并可被内化到肝细胞中。在DILI中存在高水平˙OH的情况下，DNA可被切割以释放羧基荧光素，从而导致用于˙OH检测的荧光显著增强。共聚焦荧光成像表明，该纳米探针可成功应用于监测对乙酰氨基酚或雷公藤内酯醇诱导的肝损伤所导致的高水平˙OH，这可能为DILI的预测提供一种简单而有效的方案。
