Near-Infrared Bodipy-Based Molecular Rotors for β-Amyloid Imaging In Vivo

Lijun Ma, Yujie Geng, Guoyang Zhang, Ziwei Hu, Tony D. James, Xuefei Wang, Zhuo Wang

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14 Citations (SciVal)

Abstract

β-amyloid (Aβ) is one of the important biomarkers for diagnosing Alzheimer's disease (AD). Many near-infrared probes based on the donor-π-acceptor structure have been developed to detect Aβ. Most reported Aβ probes are based on the N,N-dimethylamino group as the ideal donor, which is a widely accepted binding unit. As such, the development of fluorescent probes with improved binding units to detect Aβ is urgently required. Therefore, with this research three anchoring molecular rotor electron donors consisting of cyclic amines of different ring sizes are developed, namely five-membered ring (TPyr), six-membered ring (TPip), and seven-membered ring (THAI). These new anchored molecular rotors are connected to a 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene (BODIPY) and named TPyrBDP, TPipBDP, and THAIBDP. These probes exhibit high affinities (from 28 to 54 nm) for Aβ1–42 aggregates. The six-membered ring dye TPipBDP exhibits the highest signal-to-noise (75.5-fold) and higher affinity (28.30 ± 5.94 nm). TPipBDP can cross the blood-brain barrier and exhibits higher fluorescence enhancement with APP/PS1 (AD) double transgenic (Tg) mice than with wild-type (WT) mice.

Original languageEnglish
Article number2300733
JournalAdvanced Healthcare Materials
Volume12
Issue number25
Early online date27 Aug 2023
DOIs
Publication statusPublished - 6 Oct 2023

Bibliographical note

Funding Information:
The authors are thankful for the support from Academy of Medical Sciences Newton Advanced Fellowship (NAFR13∖1015), Beijing Natural Science Fundation (No. 7232342), National Key Research and Development Program of China (2021YFC2101500), and the China Scholarship Council. X. F. Wang thanks Beijing Natural Science Foundation (No. 8222074). TDJ wishes to thank the University of Bath and the Open Research Fund of the School of Chemistry and Chemical Engineering, Henan Normal University (2020ZD01) for support . All animal procedures were performed in accordance with the guidelines for the Care and Use of Laboratory Animals of China‐Japan Friendship Hospital, and approved by the Animal Ethics Committee of China‐Japan Friendship Hospital. The assigned approval number is zryhyy12‐20‐10‐2.

Funding

The authors are thankful for the support from Academy of Medical Sciences Newton Advanced Fellowship (NAFR13∖1015), Beijing Natural Science Fundation (No. 7232342), National Key Research and Development Program of China (2021YFC2101500), and the China Scholarship Council. X. F. Wang thanks Beijing Natural Science Foundation (No. 8222074). TDJ wishes to thank the University of Bath and the Open Research Fund of the School of Chemistry and Chemical Engineering, Henan Normal University (2020ZD01) for support . All animal procedures were performed in accordance with the guidelines for the Care and Use of Laboratory Animals of China‐Japan Friendship Hospital, and approved by the Animal Ethics Committee of China‐Japan Friendship Hospital. The assigned approval number is zryhyy12‐20‐10‐2. The authors are thankful for the support from Academy of Medical Sciences Newton Advanced Fellowship (NAFR13∖1015), Beijing Natural Science Fundation (No. 7232342), National Key Research and Development Program of China (2021YFC2101500), and the China Scholarship Council. X.F.W. thanks Beijing Natural Science Foundation (No. 8222074). T.D.J. wishes to thank the University of Bath and the Open Research Fund of the School of Chemistry and Chemical Engineering, Henan Normal University (2020ZD01) for support. All animal procedures were performed in accordance with the guidelines for the Care and Use of Laboratory Animals of China-Japan Friendship Hospital, and approved by the Animal Ethics Committee of China-Japan Friendship Hospital. The assigned approval number is zryhyy12-20-10-2.

FundersFunder number
Academy of Medical Sciences-NewtonNAFR13∖1015
Henan Normal University2020ZD01
University of Bath
China Scholarship Council
Natural Science Foundation of Beijing Municipality8222074
Beijing Municipal Natural Science Foundation7232342
National Key Research and Development Program of China2021YFC2101500
China-Japan Friendship Hospital

    Keywords

    • biological imaging
    • central nervous system
    • fluorescent probes
    • rodent models
    • β-amyloid

    ASJC Scopus subject areas

    • Biomaterials
    • Biomedical Engineering
    • Pharmaceutical Science

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