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一种用于衰老、癌症及荧光引导癌症手术中实时极性传感和靶向脂滴成像的近红外荧光探针。

An NIR Fluorescent Probe for Real-Time Polarity Sensing and Targeted Lipid Droplet Imaging in Aging, Cancer, and Fluorescence-Guided Cancer Surgery.

作者信息

Du Longjie, Li Xingyue, Li Bingxue, Ding Ru, Zhang Qisheng, Guo Yuxin, Zhang Quan, Wang Ying, Chen Juan, Zhou Xucong, Qian Zhaosheng, Zhou Jin

机构信息

Affiliated Hospital of Shandong Second Medical University (261031, School of Clinical Medicine), School of Pharmacy, School of Basic Medical Sciences, Shandong Second Medical University, Weifang 261053, China.

Weifang People's Hospital, Shandong Second Medical University, Weifang 261000, China.

出版信息

Anal Chem. 2025 Aug 12;97(31):16896-16905. doi: 10.1021/acs.analchem.5c02124. Epub 2025 Jun 26.

DOI:10.1021/acs.analchem.5c02124
PMID:40569287
Abstract

Lipid droplets (LDs) are dynamic organelles that store energy and regulate lipid metabolism and cell signaling. Their dynamic changes are closely associated with pathological conditions such as aging and cancer, making them promising biomarkers and therapeutic targets. Notably, aging and cancer are closely interconnected; however, few molecular probes can simultaneously monitor both processes. In particular, challenges remain in achieving real-time imaging of LDs dynamics under complex pathological conditions, especially in deep tissues. To address these issues, we developed a novel near-infrared (NIR) fluorescent probe, , featuring a donor-π-acceptor structure with strong intramolecular charge transfer (ICT) characteristics. demonstrates ultrahigh selectivity for LDs, high sensitivity to environmental polarity, superior photostability, and low cytotoxicity. Its NIR emission (≥650 nm) significantly reduces biological autofluorescence and enhances the tissue penetration. The detection limit of for LDs reaches 0.276 μg/mL, indicating its high analytical sensitivity. By combining imaging with commercial senescence detection kits, we achieved enhanced accuracy in assessing cellular senescence and the efficacy of antiaging drugs. Furthermore, differentiates tumors from normal tissues based on polarity variations. These features empower to serve as a multifunctional probe for both the diagnosis of aging-related diseases and fluorescence-guided tumor surgery, offering broad potential for applications in disease research, diagnostics, and therapeutics.

摘要

脂滴(LDs)是储存能量、调节脂质代谢和细胞信号传导的动态细胞器。它们的动态变化与衰老和癌症等病理状况密切相关,使其成为有前景的生物标志物和治疗靶点。值得注意的是,衰老和癌症紧密相连;然而,很少有分子探针能够同时监测这两个过程。特别是,在复杂病理条件下,尤其是在深部组织中实现脂滴动态的实时成像仍存在挑战。为了解决这些问题,我们开发了一种新型近红外(NIR)荧光探针,其具有供体-π-受体结构,具有强分子内电荷转移(ICT)特性。该探针显示出对脂滴的超高选择性、对环境极性的高敏感性、优异的光稳定性和低细胞毒性。其近红外发射(≥650 nm)显著降低生物自发荧光并增强组织穿透性。该探针检测脂滴的检测限达到0.276μg/mL,表明其具有高分析灵敏度。通过将该探针成像与商业衰老检测试剂盒相结合,我们在评估细胞衰老和抗衰老药物疗效方面实现了更高的准确性。此外,该探针基于极性变化区分肿瘤组织和正常组织。这些特性使该探针能够作为一种多功能探针,用于衰老相关疾病的诊断和荧光引导肿瘤手术,在疾病研究、诊断和治疗方面具有广阔的应用潜力。

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