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J Control Release. 2012 Oct 28;163(2):203-10. doi: 10.1016/j.jconrel.2012.09.001. Epub 2012 Sep 8.

Targeted imaging of activated caspase-3 in the central nervous system by a dual functional nano-device.

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1
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.

Abstract

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.

PMID:
22982236
DOI:
10.1016/j.jconrel.2012.09.001
[Indexed for MEDLINE]

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