Imaging lipid deposition induced by local hypoxia in degenerative aortic valve disease using a twisted intramolecular charge transfer (TICT)-based lipid droplet-targeting probe

IF 5.3 2区化学 Q1 CHEMISTRY, ANALYTICAL

Microchimica Acta Pub Date : 2025-10-18 DOI:10.1007/s00604-025-07613-z

Zheng Chai, Ming Chen, Tianyi Qu, Ying Zhang, Yunfei Ling, Shufen Li, Weihua Zhuang, Yao Wu, Wenchuang Hu, Mao Chen

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Abstract

A novel twisted intramolecular charge transfer (TICT)-based fluorescent probe, NMCTI, specifically engineered for selective visualization of lipid droplets (LDs) under hypoxic pathological conditions was developed. NMCTI exhibited an impressive Stokes shift of 112 nm, substantial solvatochromic fluorescence properties, and minimal cytotoxic effects. In cellular experiments, NMCTI demonstrated selective targeting and accumulation within LDs in HeLa cells, HUVECs and HL-1 mouse cardiomyocytes (HL-1 cells), accompanied by outstanding photostability, enabling clear and robust visualization of LDs under hypoxic conditions. Additionally, ex vivo imaging experiments on human valve tissues confirmed NMCTI's capability to clearly highlight lipid deposits in stenotic aortic valves. The imaging results were consistent with traditional histological staining, effectively differentiating pathological valves from healthy controls. These findings indicate that NMCTI can serve as a highly effective fluorescent imaging tool, significantly enhancing the detection and understanding of lipid accumulation in cardiovascular diseases, thereby contributing to improved diagnostic accuracy and therapeutic approaches for degenerative aortic valve disease (DAD).

Graphical Abstract

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基于扭曲分子内电荷转移（TICT）的脂滴靶向探针成像退行性主动脉瓣疾病局部缺氧诱导的脂质沉积

一种新型的基于扭曲分子内电荷转移（TICT）的荧光探针，NMCTI，专门用于在缺氧病理条件下脂滴（ld）的选择性可视化。NMCTI表现出令人印象深刻的112 nm的Stokes位移，实质性的溶剂致变色荧光特性和最小的细胞毒性作用。在细胞实验中，NMCTI在HeLa细胞、huvec细胞和HL-1小鼠心肌细胞（HL-1细胞）的ld内表现出选择性靶向和积累，同时具有出色的光稳定性，能够在缺氧条件下清晰而稳健地显示ld。此外，人类瓣膜组织的离体成像实验证实了NMCTI能够清晰地显示狭窄主动脉瓣内的脂质沉积。影像学结果与传统的组织学染色一致，有效地将病理瓣膜与健康对照组区分开来。这些结果表明，NMCTI可以作为一种高效的荧光成像工具，显著增强心血管疾病中脂质积累的检测和理解，从而有助于提高退行性主动脉瓣疾病（DAD）的诊断准确性和治疗方法。

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来源期刊

Microchimica Acta 化学-分析化学

CiteScore

9.80

自引率

5.30%

发文量

410

审稿时长

2.7 months

期刊介绍： As a peer-reviewed journal for analytical sciences and technologies on the micro- and nanoscale, Microchimica Acta has established itself as a premier forum for truly novel approaches in chemical and biochemical analysis. Coverage includes methods and devices that provide expedient solutions to the most contemporary demands in this area. Examples are point-of-care technologies, wearable (bio)sensors, in-vivo-monitoring, micro/nanomotors and materials based on synthetic biology as well as biomedical imaging and targeting.