Yu Bo, Pang Ziwei, Zhao Jing, Xue Jingyi, Lo Hsuan, Gu Tiancheng, Zhang Ping, Tian Jiawei, Du Guo-Qing
Department of Ultrasound, The Second Affiliated Hospital of Harbin Medical University, Harbin, 150086, China.
Department of Ultrasound, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, 510120, China.
Adv Healthc Mater. 2025 May;14(13):e2404477. doi: 10.1002/adhm.202404477. Epub 2025 Jan 24.
Coronary microvascular dysfunction (CMD) refers to clinical symptoms caused by structural and functional damage to coronary microcirculation. The timely and precise diagnosis of CMD-related myocardial ischemia is essential for improving patient prognosis. This study describes a method for the multimodal (fluorescence, ultrasonic, and photoacoustic) noninvasive imaging and treatment of CMD based on ischemic myocardium-targeting peptide (IMTP)-guided nanobubbles functionalized with indocyanine green (IMTP/ICG NBs) and characterizes their basic characteristics and in vitro imaging and targeting abilities. The IMTP/ICG NBs enable the accurate location of myocardial ischemia via photoacoustic imaging, and when loaded with tannic acid (TA), can be used to effectively treat myocardial ischemia and fibrosis in CMD mice, achieving an effect superior to that of free TA. The origin of this high therapeutic efficiency is revealed by transcriptomic and proteomic analyses. This investigation lays the groundwork for visual monitoring and the drug-targeted treatment of CMD.
冠状动脉微血管功能障碍(CMD)是指由冠状动脉微循环的结构和功能损伤引起的临床症状。及时、准确地诊断与CMD相关的心肌缺血对于改善患者预后至关重要。本研究描述了一种基于用吲哚菁绿功能化的缺血心肌靶向肽(IMTP)引导的纳米气泡(IMTP/ICG NBs)对CMD进行多模态(荧光、超声和光声)无创成像和治疗的方法,并表征了其基本特性以及体外成像和靶向能力。IMTP/ICG NBs能够通过光声成像准确地定位心肌缺血,并且当负载单宁酸(TA)时,可用于有效治疗CMD小鼠的心肌缺血和纤维化,其效果优于游离TA。转录组学和蛋白质组学分析揭示了这种高治疗效率的来源。本研究为CMD的可视化监测和药物靶向治疗奠定了基础。