Key Laboratory of Smart Drug Delivery, Ministry of Education & PLA, Department of Pharmaceutics, School of Pharmacy, Fudan University, 826 Zhangheng Road, Shanghai 201203, PR China.
J Control Release. 2012 Oct 28;163(2):203-10. doi: 10.1016/j.jconrel.2012.09.001. Epub 2012 Sep 8.
The activation of caspase-3 mediated neuron death is a common process in neurodegenerative diseases. Efficient activated caspase-3 imaging in brain would be helpful to monitor the potential lesion and intervene promptly. However, the blood-brain barrier (BBB) is the major obstacle that hinders the delivery of diagnostic agents into the brain. Herein, the fluorescence resonance energy transfer (FRET) was successfully applied to detect in vivo activated caspase-3 in apoptotic neuron with a brain-targeted nano-device, which was based on dendrigraft poly-L-lysines (DGLs) and linked with a brain-targeted peptide RVG29 as well as the caspase-3 cleavable peptide linker (DEVD). This nano-device could detect the level of caspase-3 activation in accordance with the degree of apoptosis in rat brain; meanwhile normal rat showed no fluorescence signal. The location of fluorescence signal was confirmed to accumulate more in caspase-3 activated neurons. Taken together, our nano-device would help to image activated caspase-3 in vivo and hold great promise in early diagnosis of neurodegenerative diseases.
半胱天冬酶-3 介导的神经元死亡的激活是神经退行性疾病中的一个常见过程。在大脑中有效地对激活的半胱天冬酶-3 成像将有助于监测潜在的病变并及时进行干预。然而，血脑屏障（BBB）是阻碍诊断剂进入大脑的主要障碍。在此，荧光共振能量转移（FRET）被成功地应用于通过脑靶向纳米器件在凋亡神经元中检测体内激活的半胱天冬酶-3，该纳米器件基于树枝状多聚赖氨酸（DGL）并与脑靶向肽 RVG29 以及半胱天冬酶-3 可切割肽接头（DEVD）相连。该纳米器件可以根据大鼠脑中凋亡的程度来检测半胱天冬酶-3 激活的水平；同时，正常大鼠没有荧光信号。荧光信号的位置被证实更多地聚集在激活的半胱天冬酶-3 的神经元中。总的来说，我们的纳米器件将有助于在体内对激活的半胱天冬酶-3 进行成像，并有望在神经退行性疾病的早期诊断中发挥重要作用。
