Qiao Zhen, Zhang Hongyi, Zhang Yanru, Wang KeWei
Department of Medicinal Chemistry, Qingdao University School of Pharmacy, 308 Ningxia Road, Qingdao 266071, China.
Department of Medicinal Chemistry, Qingdao University School of Pharmacy, 308 Ningxia Road, Qingdao 266071, China; Institue of Innovative Drug Discovery, Qingdao University, 38 Dengzhou Road, Qingdao 266021, China.
iScience. 2020 Jul 24;23(7):101294. doi: 10.1016/j.isci.2020.101294. Epub 2020 Jun 20.
Reliable and sensitive detection of lipase activity is essential for the early diagnosis and monitoring of acute pancreatitis or progression of digestive diseases. However, the available fluorescent probes for detection of lipase activity are only implemented in a hexane-water two-phase system due to the nature of heterogeneous catalysis of lipase, thus limiting their applications in direct imaging of lipase activity in living cells and tissues. Here we designed and synthesized a "turn on" fluorescent probe CPP based on self-assembled micelles for hydrolysis of lipase. The CPP probe exhibits high selectivity and excellent sensitivity for the detection of lipase in such a homogeneous system and is successfully applied for monitoring lipase activity in pancreatic AR42J cells, tissues, and serums. Taken together, the fluorescent CPP probe not only provides a tool for diagnostic potential in pancreatic disease but also demonstrates an application potential for micelle self-assembly-based development of biological probes.
可靠且灵敏地检测脂肪酶活性对于急性胰腺炎的早期诊断和监测或消化系统疾病的进展至关重要。然而,由于脂肪酶的非均相催化性质,现有的用于检测脂肪酶活性的荧光探针仅在正己烷 - 水两相体系中实现,从而限制了它们在活细胞和组织中脂肪酶活性直接成像的应用。在此,我们设计并合成了一种基于自组装胶束用于脂肪酶水解的“开启型”荧光探针CPP。CPP探针在这种均相体系中对脂肪酶的检测表现出高选择性和优异的灵敏度,并成功应用于监测胰腺AR42J细胞、组织和血清中的脂肪酶活性。综上所述,荧光CPP探针不仅为胰腺疾病的诊断潜力提供了一种工具,还展示了基于胶束自组装开发生物探针的应用潜力。