An NIR‐III 3P Excitable AIE Nanoprobe for High‐Quality Intravital Deep‐Brain Angiography

ABSTRACT Three‐photon (3P) fluorescence imaging (FLI) utilizing excitation wavelengths within the near‐infrared‐III (NIR‐III, 1600–1870 nm) window has emerged as a transformative modality for intravital imaging, owing to its combined advantages of excellent spatiotemporal resolution and remarkable t...

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Main Authors: Zhijun Zhang, Hui Cheng, Zengming Yang, Xiangquan Deng, Miaomiao Kang, Ping Qiu, Ke Wang, Dong Wang, Ben Zhong Tang
Format: Article
Language:English
Published: Wiley 2025-07-01
Series:Aggregate
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Online Access:https://doi.org/10.1002/agt2.70055
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author Zhijun Zhang
Hui Cheng
Zengming Yang
Xiangquan Deng
Miaomiao Kang
Ping Qiu
Ke Wang
Dong Wang
Ben Zhong Tang
author_facet Zhijun Zhang
Hui Cheng
Zengming Yang
Xiangquan Deng
Miaomiao Kang
Ping Qiu
Ke Wang
Dong Wang
Ben Zhong Tang
author_sort Zhijun Zhang
collection DOAJ
description ABSTRACT Three‐photon (3P) fluorescence imaging (FLI) utilizing excitation wavelengths within the near‐infrared‐III (NIR‐III, 1600–1870 nm) window has emerged as a transformative modality for intravital imaging, owing to its combined advantages of excellent spatiotemporal resolution and remarkable tissue penetration. High‐performance fluorescent probes are the cornerstone of high‐quality NIR‐III 3P FLI. However, the construction of such probes is often hindered by inherent trade‐offs in molecular design principles, posing significant challenges for their performance optimization and practical application. Here, we propose a straightforward and effective strategy based on π‐bridge manipulation to reconcile those competing molecular design parameters and substantially enhance 3P fluorescence properties. Leveraging this approach, a robust AIE‐active small molecule, named TSSID, was developed, which exhibits bright NIR‐I (700–950 nm) emission under 1665 nm NIR‐III 3P excitation when formulated into nanoparticles (NPs). Remarkably, upon retro‐orbital injection into mice following craniotomy, TSSID NPs achieved the best performance in deep‐brain angiography among all reported organic 3P materials in terms of vascular imaging depth, signal‐to‐background ratio, spatial resolution, and hemodynamic imaging depth. Additionally, TSSID NPs demonstrated outstanding biocompatibility through systematic biosafety evaluations. This study provides an excellent imaging agent and useful molecular design philosophy, facilitating the development of advanced organic 3P FLI probes.
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spelling doaj-art-f091f37638c8422a9317c6cc1e4fd5042025-08-20T03:51:18ZengWileyAggregate2692-45602025-07-0167n/an/a10.1002/agt2.70055An NIR‐III 3P Excitable AIE Nanoprobe for High‐Quality Intravital Deep‐Brain AngiographyZhijun Zhang0Hui Cheng1Zengming Yang2Xiangquan Deng3Miaomiao Kang4Ping Qiu5Ke Wang6Dong Wang7Ben Zhong Tang8Center for AIE Research, Guangdong Provincial Key Laboratory of New Energy Materials Service Safety, College of Materials Science and Engineering Shenzhen University Shenzhen ChinaKey Laboratory of Optoelectronic Devices and Systems of Ministry of Education and Guangdong Province, College of Physics and Optoelectronic Engineering Shenzhen University Shenzhen ChinaCenter for AIE Research, Guangdong Provincial Key Laboratory of New Energy Materials Service Safety, College of Materials Science and Engineering Shenzhen University Shenzhen ChinaKey Laboratory of Optoelectronic Devices and Systems of Ministry of Education and Guangdong Province, College of Physics and Optoelectronic Engineering Shenzhen University Shenzhen ChinaCenter for AIE Research, Guangdong Provincial Key Laboratory of New Energy Materials Service Safety, College of Materials Science and Engineering Shenzhen University Shenzhen ChinaKey Laboratory of Optoelectronic Devices and Systems of Ministry of Education and Guangdong Province, College of Physics and Optoelectronic Engineering Shenzhen University Shenzhen ChinaKey Laboratory of Optoelectronic Devices and Systems of Ministry of Education and Guangdong Province, College of Physics and Optoelectronic Engineering Shenzhen University Shenzhen ChinaCenter for AIE Research, Guangdong Provincial Key Laboratory of New Energy Materials Service Safety, College of Materials Science and Engineering Shenzhen University Shenzhen ChinaGuangdong Basic Research Center of Excellence for Aggregate Science, School of Science and Engineering, Shenzhen Institute of Aggregate Science and Technology The Chinese University of Hong Kong, Shenzhen (CUHK‐Shenzhen) Shenzhen Guangdong ChinaABSTRACT Three‐photon (3P) fluorescence imaging (FLI) utilizing excitation wavelengths within the near‐infrared‐III (NIR‐III, 1600–1870 nm) window has emerged as a transformative modality for intravital imaging, owing to its combined advantages of excellent spatiotemporal resolution and remarkable tissue penetration. High‐performance fluorescent probes are the cornerstone of high‐quality NIR‐III 3P FLI. However, the construction of such probes is often hindered by inherent trade‐offs in molecular design principles, posing significant challenges for their performance optimization and practical application. Here, we propose a straightforward and effective strategy based on π‐bridge manipulation to reconcile those competing molecular design parameters and substantially enhance 3P fluorescence properties. Leveraging this approach, a robust AIE‐active small molecule, named TSSID, was developed, which exhibits bright NIR‐I (700–950 nm) emission under 1665 nm NIR‐III 3P excitation when formulated into nanoparticles (NPs). Remarkably, upon retro‐orbital injection into mice following craniotomy, TSSID NPs achieved the best performance in deep‐brain angiography among all reported organic 3P materials in terms of vascular imaging depth, signal‐to‐background ratio, spatial resolution, and hemodynamic imaging depth. Additionally, TSSID NPs demonstrated outstanding biocompatibility through systematic biosafety evaluations. This study provides an excellent imaging agent and useful molecular design philosophy, facilitating the development of advanced organic 3P FLI probes.https://doi.org/10.1002/agt2.70055aggregation‐induced emissionintravital deep‐brain angiographymolecular engineeringNIR‐I fluorescence emissionNIR‐III three‐photon excitation
spellingShingle Zhijun Zhang
Hui Cheng
Zengming Yang
Xiangquan Deng
Miaomiao Kang
Ping Qiu
Ke Wang
Dong Wang
Ben Zhong Tang
An NIR‐III 3P Excitable AIE Nanoprobe for High‐Quality Intravital Deep‐Brain Angiography
Aggregate
aggregation‐induced emission
intravital deep‐brain angiography
molecular engineering
NIR‐I fluorescence emission
NIR‐III three‐photon excitation
title An NIR‐III 3P Excitable AIE Nanoprobe for High‐Quality Intravital Deep‐Brain Angiography
title_full An NIR‐III 3P Excitable AIE Nanoprobe for High‐Quality Intravital Deep‐Brain Angiography
title_fullStr An NIR‐III 3P Excitable AIE Nanoprobe for High‐Quality Intravital Deep‐Brain Angiography
title_full_unstemmed An NIR‐III 3P Excitable AIE Nanoprobe for High‐Quality Intravital Deep‐Brain Angiography
title_short An NIR‐III 3P Excitable AIE Nanoprobe for High‐Quality Intravital Deep‐Brain Angiography
title_sort nir iii 3p excitable aie nanoprobe for high quality intravital deep brain angiography
topic aggregation‐induced emission
intravital deep‐brain angiography
molecular engineering
NIR‐I fluorescence emission
NIR‐III three‐photon excitation
url https://doi.org/10.1002/agt2.70055
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