Gao Tingting, Gao Siqi, Qiao Maolin, Lu Chuanlong, Wang Heng, Zhang Hongjiu, Li Lizheng, Wang Shule, Zhang Ruijing, Dong Honglin
The Second Clinical Medical College, Shanxi Medical University, Taiyuan 030000, China.
Centre for Transplant and Renal Research, Westmead Institute for Medical Research, The University of Sydney, Sydney 201101, Australia.
Pharmaceutics. 2025 Mar 30;17(4):444. doi: 10.3390/pharmaceutics17040444.
Atherosclerotic diseases, including coronary heart disease and cerebrovascular disease, are leading causes of morbidity and mortality worldwide. Atherosclerosis is a chronic vascular condition marked by the accumulation of lipid plaque within arterial walls. These plaques can become unstable and rupture, leading to thrombosis and subsequent cardiovascular events. Therefore, early identification of vulnerable plaque is critical for preventing such events. This study aims to develop a novel imaging platform for atherosclerotic plaque by designing a molecular imaging probe based on fluorescent molecules that target lipid necrotic cores. The goal is to specifically detect high-risk plaque, enabling early diagnosis and intervention. Bioinformatic analysis and immunofluorescence were used to detect CD36 expression in human carotid plaque. CD36pep-ICG was synthesized using the Fmoc solid-phase peptide method. A series of experiments was conducted to characterize the probe's properties. To assess imaging performance, probe concentration gradients were tested using FLI equipment. Ex vivo imaging was performed on atherosclerotic mice and treatment models to evaluate the probe's targeting ability and effectiveness in monitoring disease progression. The CD36 expression was significantly elevated in the core of plaque compared to distal regions. The CD36pep-ICG probe, specifically designed to target lipids, was successfully synthesized and exhibited excellent fluorescence properties. In animal models, FLI imaging demonstrated that the CD36pep-ICG probe selectively accumulated in atherosclerotic plaque, enabling precise plaque detection. Moreover, the probe was used to monitor the therapeutic efficacy of anti-atherosclerotic drugs. The CD36pep-ICG probe developed in this study is an effective molecular imaging tool for the specific identification of vulnerable atherosclerotic plaque, offering a novel approach for early diagnosis and treatment. Additionally, the probe shows promise in tracking the therapeutic effects of the drug, potentially advancing the precision treatment of cardiovascular diseases.
动脉粥样硬化疾病，包括冠心病和脑血管疾病，是全球发病和死亡的主要原因。动脉粥样硬化是一种慢性血管疾病，其特征是动脉壁内脂质斑块的积累。这些斑块可能会变得不稳定并破裂，导致血栓形成和随后的心血管事件。因此，早期识别易损斑块对于预防此类事件至关重要。本研究旨在通过设计一种基于靶向脂质坏死核心的荧光分子的分子成像探针，开发一种用于动脉粥样硬化斑块的新型成像平台。目标是特异性检测高危斑块，实现早期诊断和干预。使用生物信息学分析和免疫荧光检测人颈动脉斑块中CD36的表达。采用Fmoc固相肽法合成CD36pep-ICG。进行了一系列实验来表征该探针的特性。为了评估成像性能，使用FLI设备测试了探针浓度梯度。在动脉粥样硬化小鼠和治疗模型上进行离体成像，以评估该探针的靶向能力和监测疾病进展的有效性。与远端区域相比，斑块核心的CD36表达显著升高。专门设计用于靶向脂质的CD36pep-ICG探针成功合成，并表现出优异的荧光特性。在动物模型中，FLI成像表明CD36pep-ICG探针选择性地积聚在动脉粥样硬化斑块中，能够精确检测斑块。此外，该探针还用于监测抗动脉粥样硬化药物的治疗效果。本研究中开发的CD36pep-ICG探针是一种有效的分子成像工具，用于特异性识别易损动脉粥样硬化斑块，为早期诊断和治疗提供了一种新方法。此外，该探针在跟踪药物治疗效果方面显示出前景，可能推动心血管疾病的精准治疗。
