State Key Laboratory for Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, Hunan University, Changsha 410082, China.
Department of Cardiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China.
Sci Adv. 2023 Oct 13;9(41):eadh1037. doi: 10.1126/sciadv.adh1037.
Oxidative stress is integral in the development of atherosclerosis, but knowledge of how oxidative stress affects atherosclerosis remains insufficient. Here, we design a multiplexed diagnostic tool that includes two functions (photoacoustic imaging and urinalysis), for assessing intraplaque and urinary malondialdehyde (MDA), a well-recognized end-product of oxidative stress. Molecular design is conducted to develop the first near-infrared MDA-responsive molecule (MRM). Acid-unlocked ratiometric photoacoustic nanoprobe is designed to report intraplaque MDA, enabling it to reflect plaque burden. Furthermore, MRM is tailored for urinary MDA detection with excellent specificity in a blind study. Moreover, we found a significant difference in urinary MDA between healthy adults and atherosclerotic patients (more than 600 participants). Combining these two functions, such a multiplexed diagnostic tool can dynamically report intraplaque and systemic oxidative stress levels during atherosclerosis progression, pneumonia infection, and drug treatment in atherosclerotic mice, which is promising for the auxiliary diagnosis of atherosclerosis.
氧化应激是动脉粥样硬化发展过程中的一个重要因素，但目前对于氧化应激如何影响动脉粥样硬化的认识仍然不足。在这里，我们设计了一种多重诊断工具，包括两个功能（光声成像和尿液分析），用于评估斑块内和尿液中的丙二醛（MDA），MDA 是氧化应激的公认终产物。通过分子设计，我们开发了第一个近红外 MDA 响应分子（MRM）。设计了酸解锁的比率型光声纳米探针来报告斑块内 MDA，使其能够反映斑块负担。此外，MRM 经过精心设计，可用于尿液 MDA 的检测，在盲法研究中具有优异的特异性。此外，我们在健康成年人和动脉粥样硬化患者（超过 600 名参与者）之间的尿液 MDA 中发现了显著差异。结合这两种功能，这种多重诊断工具可以在动脉粥样硬化小鼠的动脉粥样硬化进展、肺炎感染和药物治疗期间动态报告斑块内和系统性氧化应激水平，这对于动脉粥样硬化的辅助诊断具有很大的应用前景。
