TY - JOUR
T1 - Deep-Brain Three-Photon Imaging Enabled by Aggregation-Induced Emission Luminogens with Near-Infrared-III Excitation
AU - Xu, Zhourui
AU - Zhang, Zhijun
AU - Deng, Xiangquan
AU - Li, Jiangao
AU - Jiang, Yihang
AU - Law, Wing Cheung
AU - Yang, Chengbin
AU - Zhang, Wanjian
AU - Chen, Xiaolin
AU - Wang, Ke
AU - Wang, Dong
AU - Xu, Gaixia
N1 - Funding Information:
This work was supported by National Natural Science Foundation of China (81772002, 52122317, 22175120, 31871442, and 61975126), Natural Science Foundation of Guangdong Province (2021A1010012159, 2019A1515012163, and 2020B1515020011), Shenzhen Stability Support Program for Universities (20200812122708001), Start-up Grant from Shenzhen University (2019136) and The Postgraduate Innovation Development Fund Project of Shenzhen University (315-0000470832). The authors also thank Instrument Analysis Centre of Shenzhen University for the assistance with imaging analysis. All animal operations complied with the regulations of the Animal Ethical and Welfare Committee of Shenzhen University (AEWC-SZU).
Publisher Copyright:
© 2022 American Chemical Society.
PY - 2022/4/26
Y1 - 2022/4/26
N2 - Understanding the morphology and hemodynamics of cerebral vasculature at large penetration depths and microscale resolution is fundamentally important to decipher brain diseases. Among the various imaging technologies, three-photon (3P) microscopy is of significance by virtue of its deep-penetrating capability and submicron resolution, which especially benefits in vivo vascular imaging. Aggregation-induced emission luminogens (AIEgens) have been recognized to be extraordinarily powerful as 3P probes. However, systematic studies on the structure-performance relationship of 3P AIEgens have been seldom reported. Herein, a series of AIEgens has been designed and synthesized. By intentionally introducing benzene rings onto electron donors (D) and acceptors (A), the molecular distortion, conjugation strength, and the D-A relationship can be facilely manipulated. Upon encapsulation with DSPE-PEG2000, the optimized AIEgens are successfully applied for 3P microscopy with emission in the far-red/near-infrared-I (NIR-I, 700-950 nm) region under the near-infrared-III (NIR-III, 1600-1870 nm) excitation. Impressively, using mice with an opened skull, vasculature within 1700 μm and a microvessel with a diameter of 2.2 μm in deep mouse brain were clearly visualized. In addition, the hemodynamics of blood vessels were well-characterized. Thus, this work not only proposes a molecular design strategy of 3P AIEgens but also promotes the performance of 3P imaging in cerebral vasculature.
AB - Understanding the morphology and hemodynamics of cerebral vasculature at large penetration depths and microscale resolution is fundamentally important to decipher brain diseases. Among the various imaging technologies, three-photon (3P) microscopy is of significance by virtue of its deep-penetrating capability and submicron resolution, which especially benefits in vivo vascular imaging. Aggregation-induced emission luminogens (AIEgens) have been recognized to be extraordinarily powerful as 3P probes. However, systematic studies on the structure-performance relationship of 3P AIEgens have been seldom reported. Herein, a series of AIEgens has been designed and synthesized. By intentionally introducing benzene rings onto electron donors (D) and acceptors (A), the molecular distortion, conjugation strength, and the D-A relationship can be facilely manipulated. Upon encapsulation with DSPE-PEG2000, the optimized AIEgens are successfully applied for 3P microscopy with emission in the far-red/near-infrared-I (NIR-I, 700-950 nm) region under the near-infrared-III (NIR-III, 1600-1870 nm) excitation. Impressively, using mice with an opened skull, vasculature within 1700 μm and a microvessel with a diameter of 2.2 μm in deep mouse brain were clearly visualized. In addition, the hemodynamics of blood vessels were well-characterized. Thus, this work not only proposes a molecular design strategy of 3P AIEgens but also promotes the performance of 3P imaging in cerebral vasculature.
KW - aggregation-induced emission
KW - brain vasculature imaging
KW - hemodynamic imaging
KW - NIR-III excitation
KW - three-photon imaging
UR - http://www.scopus.com/inward/record.url?scp=85127352081&partnerID=8YFLogxK
U2 - 10.1021/acsnano.2c01349
DO - 10.1021/acsnano.2c01349
M3 - Journal article
AN - SCOPUS:85127352081
SN - 1936-0851
VL - 16
SP - 6712
EP - 6724
JO - ACS Nano
JF - ACS Nano
IS - 4
ER -