Abstract：
Atherosclerosis is a primary global health concern due to its high morbidity and mortality. This disease is characterized by a complex interplay of chronic inflammation, oxidative stress, and proteolytic enzymes. Traditional imaging techniques struggle to capture the dynamic biochemical processes within atherosclerotic plaques. Herein, we have developed a novel unimolecular photoacoustic probe (UMAPP) that combines specific recognition sites for neutrophil elastase (NE) and the redox pair O2•‒/GSH into a cohesive molecular platform, allowing in vivo monitoring of oxidative stress and activated neutrophils within plaques. UMAPP features a boron-dipyrromethene (BODIPY) core linked to a hydrophilic NE-cleavable tetrapeptide, and dual oxidative stress-responsive catechol moieties, enabling NE-mediated modulation of photoinduced electron transfer, affecting the photoacoustic intensity at 685 nm (PA685), while oxidation and reduction of the catechol groups by O2•‒ and GSH lead to reversible, ratiometric changes in the photoacoustic spectrum. Preliminary applications of UMAPP have successfully differentiated between atherosclerotic and healthy mice, assessed the impact of pneumonia on plaque composition, and validated the probe\'s efficacy in drug-treatment studies, detecting molecular changes prior to observable histopathological alterations. UMAPP\'s integrated molecular imaging approach holds significant promise for advancing the diagnosis and management of atherosclerosis by enabling earlier and more precise detection of vulnerable plaques.
摘要：
动脉粥样硬化由于其高发病率和死亡率而成为主要的全球健康问题。这种疾病的特征是慢性炎症的复杂相互作用，氧化应激，和蛋白水解酶。传统的成像技术难以捕获动脉粥样硬化斑块内的动态生化过程。在这里，我们开发了一种新型的单分子光声探针（UMAPP），它将中性粒细胞弹性蛋白酶（NE）和氧化还原对O2•-/GSH的特定识别位点结合到一个粘性分子平台中，允许体内监测斑块内的氧化应激和活化的中性粒细胞。UMAPP具有与亲水性NE可裂解四肽连接的硼-二吡咯亚甲基（BODIPY）核心，和双重氧化应激反应性儿茶酚部分，使NE介导的光诱导电子转移调制，影响685nm处的光声强度（PA685），而邻苯二酚基团被O2•-和GSH的氧化和还原导致可逆的，光声光谱的比率变化。UMAPP的初步应用已成功区分了动脉粥样硬化小鼠和健康小鼠，评估肺炎对斑块组成的影响，并验证了探针在药物治疗研究中的功效，在可观察到的组织病理学改变之前检测分子变化。UMAPP的整合分子成像方法通过能够更早、更精确地检测易损斑块，对推进动脉粥样硬化的诊断和管理具有重要的前景。
