Turn-on chemiluminescence probes and dual-amplification of signal for detection of amyloid beta species in vivo

Jing Yang, Wei Yin, Richard Van, Keyi Yin, Peng Wang, Chao Zheng, Biyue Zhu, Kathleen Ran, Can Zhang, Mohanraja Kumar, Yihan Shao and Chongzhao Ran ()
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Jing Yang: Massachusetts General Hospital/Harvard Medical School, Room 2301, Building 149, Charlestown
Wei Yin: Massachusetts General Hospital/Harvard Medical School, Room 2301, Building 149, Charlestown
Richard Van: University of Oklahoma
Keyi Yin: Massachusetts General Hospital/Harvard Medical School, Room 2301, Building 149, Charlestown
Peng Wang: Massachusetts General Hospital/Harvard Medical School, Room 2301, Building 149, Charlestown
Chao Zheng: Massachusetts General Hospital/Harvard Medical School, Room 2301, Building 149, Charlestown
Biyue Zhu: Massachusetts General Hospital/Harvard Medical School, Room 2301, Building 149, Charlestown
Kathleen Ran: Massachusetts General Hospital/Harvard Medical School, Room 2301, Building 149, Charlestown
Can Zhang: Massachusetts General Hospital and Harvard Medical School
Mohanraja Kumar: Massachusetts Institute of Technology
Yihan Shao: University of Oklahoma
Chongzhao Ran: Massachusetts General Hospital/Harvard Medical School, Room 2301, Building 149, Charlestown

Nature Communications, 2020, vol. 11, issue 1, 1-14

Abstract: Abstract Turn-on fluorescence imaging is routinely studied; however, turn-on chemiluminescence has been rarely explored for in vivo imaging. Herein, we report the design and validation of chemiluminescence probe ADLumin-1 as a turn-on probe for amyloid beta (Aβ) species. Two-photon imaging indicates that ADLumin-1 can efficiently cross the blood–brain barrier and provides excellent contrast for Aβ plaques and cerebral amyloid angiopathy. In vivo brain imaging shows that the chemiluminescence signal of ADLumin-1 from 5-month-old transgenic 5xFAD mice is 1.80-fold higher than that from the age-matched wild-type mice. Moreover, we demonstrate that it is feasible to further dually-amplify signal via chemiluminescence resonance energy transfer (DAS-CRET) using two non-conjugated smart probes (ADLumin-1 and CRANAD-3) in solutions, brain homogenates, and in vivo whole brain imaging. Our results show that DAS-CRET can provide a 2.25-fold margin between 5-month-old 5xFAD mice and wild type mice. We believe that our strategy could be extended to other aggregating-prone proteins.

Date: 2020
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DOI: 10.1038/s41467-020-17783-4

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