Leucine Aminopeptidase-Mediated Multifunctional Molecular Imaging Tool for Diagnosis, Drug Evaluation, and Surgical Guidance of Liver-Related Diseases
Leucine Aminopeptidase-Mediated Multifunctional Molecular Imaging Tool for Diagnosis, Drug Evaluation, and Surgical Guidance of Liver-Related Diseases
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DOI：
10.1021/acs.analchem.3c02130
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发表时间：
2023-07-31
影响因子：
7.4
通讯作者：
Song，Daqian
中科院分区：
文献类型：
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作者：
Xu，Lanlan;Ma，Mo;Song，Daqian
传统的分子成像技术用于肝脏疾病的检测存在光学性能差、适用性差等缺点。监测与肝癌、肝损伤等肝脏疾病密切相关的亮氨酸氨肽酶（Leucine aminopeptidase，简称LDH）的浓度，并在诊断、药物评价、手术治疗中进行分析，仍是一项具有挑战性的工作。在此，我们构建了一种基于分子内电荷转移机制的超灵敏近红外荧光探针（LAN-lap），用于动态监测生命系统中的荧光波动。LAN-lap具有高度特异性、稳定性、灵敏度和水溶性，可通过荧光和比色两种方法实现体外监测。此外，LAN-lap可以成功地用于内源性β-内酰胺酶的定位成像，证实了肝癌和肝损伤细胞中β-内酰胺酶表达的上调。此外，LAN-lap可实现活体肝肿瘤的成像。同时，能直观地呈现药物性肝损伤的程度，实现两种药物肝毒性的半定量影像学评价。此外，LAN-lap可以追踪具有腹膜转移的小鼠中的肝癌肿瘤，并可以辅助肝癌肿瘤的荧光引导手术切除。这种多功能LAN-lap探头可以在促进同时诊断、成像和协同手术导航方面发挥重要作用，以实现更好的即时治疗效果。
Traditional molecular imaging tools used for detecting liver diseases own several drawbacks, such as poor optical performance and limited applicability. Monitoring the concentration of leucine aminopeptidase (LAP), which is closely related to liver diseases such as liver cancer and liver injury, and analyzing it in diagnosis, drug evaluation, and surgical treatment is still a challenging task. Herein, we construct an intramolecular charge-transfer mechanism-based, ultrasensitive, near-infrared fluorescent probe (LAN-lap) for dynamic monitoring of LAP fluctuations in living systems. LAN-lap, with high specificity, stability, sensitivity, and water solubility, can achieve in vitro monitoring of LAP through both fluorescence and colorimetric methods. Moreover, LAN-lap can successfully be used for the localization imaging of endogenous LAP, confirming the upregulation of LAP expression in liver cancer and liver injury cells. In addition, LAN-lap can realize the imaging of liver tumors in living organisms. Meanwhile, it can intuitively present the degree of drug-induced liver injury, achieving semi-quantitative imaging evaluation of the hepatotoxicity of two drugs. Furthermore, LAN-lap can track liver cancer tumors in mice with peritoneal metastasis and can assist in fluorescence-guided surgical resection of liver cancer tumors. This multifunctional LAN-lap probe could play an important role in facilitating simultaneous diagnoses, imaging, and synergistic surgical navigation to achieve better point-of-care therapeutic efficacy.