Liu Yongchao, Teng Lili, Xu Chengyan, Liu Hong-Wen, Xu Shuai, Guo Haowei, Yuan Lin, Zhang Xiao-Bing
State Key Laboratory of Chemo/Biosensing and Chemometrics , College of Chemistry and Chemical Engineering , Collaborative Innovation Center for Chemistry and Molecular Medicine , Hunan University , Changsha , 410082 , P. R. China . Email:
Chem Sci. 2019 Oct 16;10(47):10931-10936. doi: 10.1039/c9sc03628h. eCollection 2019 Dec 21.
Molecular probes activated by a single enzyme have been extensively used in bioimaging and disease diagnosis; however, imaging and identification in an accurate manner remains a challenge for such probes. Here, based on the specificity of enzyme recognition, we engineered a "double-locked" and enzyme-activated molecular probe () for accurate bioimaging and hepatopathy differentiation. Triggered by the successive reactions with leucine aminopeptidase (LAP, first "key") and monoamine oxidase (MAO, second "key"), the emissive fluorophore () was released. can be activated only in the presence of both LAP and MAO and can be silenced when either enzyme is inhibited. Benefiting from the "double-locked" strategy, showed higher accuracy for imaging of drug-induced liver injury (DILI) than the "single-locked" probe. With serum testing, showed significant differences in mouse models of both CCl-induced liver cirrhosis and DILI. Significantly, can be applied to accurately distinguish serum samples from clinical patients with different hepatopathies. Our smart molecular probe may hold great potential for hepatopathy diagnosis and clinical transformation.
由单一酶激活的分子探针已广泛应用于生物成像和疾病诊断；然而，以准确的方式进行成像和识别对此类探针而言仍然是一项挑战。在此，基于酶识别的特异性，我们设计了一种用于精确生物成像和肝病鉴别诊断的“双锁”且酶激活的分子探针（）。通过与亮氨酸氨肽酶（LAP，第一把“钥匙”）和单胺氧化酶（MAO，第二把“钥匙”）的连续反应触发，发射荧光团（）被释放。只有在同时存在LAP和MAO时才能被激活，而当任何一种酶被抑制时则会沉默。受益于“双锁”策略，与“单锁”探针相比，在药物性肝损伤（DILI）成像方面显示出更高的准确性。通过血清检测，在四氯化碳诱导的肝硬化和DILI小鼠模型中均显示出显著差异。重要的是，可应用于准确区分不同肝病临床患者的血清样本。我们的智能分子探针在肝病诊断和临床转化方面可能具有巨大潜力。
