Turn-on chemiluminescence probes and dual-amplification of signal for detection of amyloid beta species in vivo
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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 d ually- a mplify s ignal via c hemiluminescence r esonance e nergy t ransfer (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.
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Cinnamic derivatives can cross the blood-brain barrier and insert into the beta sheet of amyloid β proteins.
“Cinnamic derivatives can cross the BBB and insert into the beta sheet of amyloid β proteins41.”
From Blood–brain-barrier-crossing lipid nanoparticles for mRNA delivery to the central nervous system (2025) · cites this paper as [41]
The Results (In vivo imaging with ADLumin-1; page unavailable) report that ADLumin-1 crossed the blood–brain barrier in mice. The Results (Design and synthesis of ADLumin-1; page unavailable) say its binding moiety has the potential to insert into Aβ beta sheets, but the paper does not identify the probes as cinnamic derivatives or establish insertion as a demonstrated fact. (LLM, conf=0.84)
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- Authors
- Yang, J., Yin, W., Van, R., Yin, K., Wang, P., Zheng, C., Zhu, B., Ran, K., Zhang, C., Kumar, M., Shao, Y., & Ran, C.
- Affiliations
- Harvard University (US)
- University of Oklahoma (US)
- Massachusetts Institute of Technology (US)
- Corresponding author
- Ran, Chongzhao
- ORCID
- Venue
- Nature Communications
- Published
- 2020-08-13
- Volume
- 11
- Issue
- 1
- Pages
- 4052-4052
- ISSN
- 2041-1723 (ISSN-L)
- PMC
- PMC7426431
- OpenAlex
- W3048903908
- Cited by
- 123
- References
- 73
- Citations by year
- 2026: 16 · 2025: 16 · 2024: 24 · 2023: 24 · 2022: 13 · 2021: 27 · 2020: 3
- FWCI
- 10.07
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Nature Communications (publishedVersion, cc-by)
- ChemRxiv (acceptedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Figshare (submittedVersion, cc-by-nc-nd)
- Funders
- U.S. Department of Health & Human Services | NIH | National Institute on Aging (R21AG059134, R01AG055413)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Physical Sciences › Chemistry › Spectroscopy › Molecular Sensors and Ion Detection
- Physical Sciences › Materials Science › Materials Chemistry › Luminescence and Fluorescent Materials
- Keywords
- chemiluminescence probe, amyloid-beta detection, chemiluminescence resonance energy transfer, two-photon imaging, blood-brain barrier penetration, cerebral amyloid angiopathy, amyloid plaques, 5xFAD mice, in vivo brain imaging
- MeSH terms
- Animals, Luminescent Measurements, Amyloid beta-Peptides, Luminescence, Mice, Molecular Imaging, Optical Imaging, Protein Aggregates
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