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It is of great significance to study the brain structure and function in deep-tissue for neuroscience research and bio-medical applications because of the urgent demand for precise theranostics. Three-photon fluorescence microscopic (3PFM) bioimaging excited by the light in near-infrared IIb (NIR-IIb, 1,500-1,700 nm) spectral region is one of the most promising imaging techniques with the advantages of high spatial resolution, large imaging depth, and reduced scattering. Herein, a type of NIR-IIb light excitable deep-red emissive semiconducting polymer dots (P-dots) with bright 3PF and large three-photon absorption cross-section (σ3) at 1,550 nm was prepared. Then the P-dots were functionalized with polystyrene polymer polystyrene graft ethylene oxide functionalized with carboxyl groups (PS-PEG-COOH) and modified with NH2-poly(ethylene glycol) (PEG) to synthesis photochemically stable and biocompatible P-dots nanoparticles (NPs). Further the P-dots NPs were utilized for in vivo 3PFM bioimaging of cerebral vasculature with and without the brain skull under 1,550 nm femtosecond (fs) laser excitation. In vivo 3PFM bioimaging of the mice cerebral vasculature at various vertical depths was obtained. Moreover, a vivid three-dimensional structure of the mice vascular architecture beneath the skull was reconstructed. At the depth of 350 μm beneath the brain skull, 3.8 µm blood vessels could still be clearly recognized. NIR-IIb excitable P-dots assisted 3PFM bioimaging has great potential in accurate deep tissue bioimaging.


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NIR-IIb excitable bright polymer dots with deep-red emission for in vivo through-skull three-photon fluorescence bioimaging

Show Author's information Nuernisha Alifu1,2Abudureheman Zebibula3Hequn Zhang2,4Huwei Ni2Liang Zhu2,4Wang Xi4( )Yalun Wang2Xueliang Zhang1( )Changfeng Wu5Jun Qian2( )
School of Medical Engineering and Technology, Xinjiang Medical University, Urumqi 830011, China
State Key Laboratory of Modern Optical Instrumentations, Centre for Optical and Electromagnetic Research, College of Optical Science and Engineering, Zhejiang University, Hangzhou 310058, China
Department of Urology, Sir Run-Run Shaw Hospital College of Medicine, Zhejiang University, Hangzhou 310016, China
Interdisciplinary Institute of Neuroscience and Technology, the Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310020, China
Department of Biomedical Engineering, South University of Science and Technology, Shenzhen 518055, China

Abstract

It is of great significance to study the brain structure and function in deep-tissue for neuroscience research and bio-medical applications because of the urgent demand for precise theranostics. Three-photon fluorescence microscopic (3PFM) bioimaging excited by the light in near-infrared IIb (NIR-IIb, 1,500-1,700 nm) spectral region is one of the most promising imaging techniques with the advantages of high spatial resolution, large imaging depth, and reduced scattering. Herein, a type of NIR-IIb light excitable deep-red emissive semiconducting polymer dots (P-dots) with bright 3PF and large three-photon absorption cross-section (σ3) at 1,550 nm was prepared. Then the P-dots were functionalized with polystyrene polymer polystyrene graft ethylene oxide functionalized with carboxyl groups (PS-PEG-COOH) and modified with NH2-poly(ethylene glycol) (PEG) to synthesis photochemically stable and biocompatible P-dots nanoparticles (NPs). Further the P-dots NPs were utilized for in vivo 3PFM bioimaging of cerebral vasculature with and without the brain skull under 1,550 nm femtosecond (fs) laser excitation. In vivo 3PFM bioimaging of the mice cerebral vasculature at various vertical depths was obtained. Moreover, a vivid three-dimensional structure of the mice vascular architecture beneath the skull was reconstructed. At the depth of 350 μm beneath the brain skull, 3.8 µm blood vessels could still be clearly recognized. NIR-IIb excitable P-dots assisted 3PFM bioimaging has great potential in accurate deep tissue bioimaging.

Keywords: semiconducting polymer dots (P-dots), near-infrared IIb (NIR-IIb), three-photon fluorescence microscopic (3PFM) bioimaging, cerebral vasculature, through-skull

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Publication history
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Acknowledgements

Publication history

Received: 08 April 2020
Revised: 22 May 2020
Accepted: 24 May 2020
Published: 30 June 2020
Issue date: October 2020

Copyright

© Tsinghua University Press and Springer-Verlag GmbH Germany, part of Springer Nature 2020

Acknowledgements

This work was supported by the National Natural Science Foundation of China (Nos. 61735016, 61975172, and 91632105), Zhejiang Provincial Natural Science Foundation of China (Nos. LR17F050001 and LY17C090005), the Fundamental Research Funds for the Central Universities and State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia Fund (No. SKL-HIDCA-2019-3).

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