Development of near-infrared chemiluminescent probes for in vivo imaging

Molecular imaging is an indispensable tool in deciphering and monitoring the physiological and pathological processes at the subcellular or cellular level. For visualization and quantification of biological processes, multiple imaging modalities are developed along with different image-capture techn...

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Main Author: Huang, Jingsheng
Other Authors: Pu Kanyi
Format: Thesis-Doctor of Philosophy
Language:English
Published: Nanyang Technological University 2022
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Online Access:https://hdl.handle.net/10356/163961
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spelling sg-ntu-dr.10356-1639612023-01-12T01:24:35Z Development of near-infrared chemiluminescent probes for in vivo imaging Huang, Jingsheng Pu Kanyi School of Chemical and Biomedical Engineering kypu@ntu.edu.sg Science Engineering::Chemical engineering Molecular imaging is an indispensable tool in deciphering and monitoring the physiological and pathological processes at the subcellular or cellular level. For visualization and quantification of biological processes, multiple imaging modalities are developed along with different image-capture techniques, including ultrasound (US), computed tomography (CT), magnetic resonance (MRI), and positron emission tomography (PET) technologies. Among these different imaging modalities, optical imaging outperforms others in the high-throughput capacity, less radiative toxicity, and low-cost equipment. Moreover, in contrast to anatomical imaging and biopsy imaging, optical real-time imaging shows great advantages in time-consuming, high resolution, and noninvasiveness without pain for diagnosis and treatment in the clinic. There are two types of optical imaging agents, namely inorganic and organic imaging agents. Inorganic agents always suffer from biotoxicity resulting from leakage of metal ions and difficult biodegradability, which impede their further application in translational applications. Organic optical agents exhibit an excellent sensitivity for biomarker detection at the subcellular levels, facilitating both pre-clinical and clinical applications. Despite these merits, optical imaging is still confronted with narrow penetration tissue depth (< 1 cm) and compromised imaging quality (low signal-to-background ratio, SBR) because of tissue autofluorescence caused by real-time excitation. To address the mentioned issues, other novel imaging modalities have been developed, especially second near-infrared-II (NIR-II) fluorescence imaging and chemiluminescence (CL) imaging. NIR-II fluorescence imaging is booming along with the development of emerging NIR-II Imaging techniques in recent years. NIR-II fluorophores (emission wavelength: 1,000-1,700 nm) exhibit superior optical properties owing to diminished background autofluorescence and reduced light scattering. Unfortunately, NIR-II fluorophores always suffer from low fluorescence quantum yield and show difficulties in the design of activatable probes, causing low SBR because of the “always-on” signal. Interestingly, chemiluminescence imaging can offer another strategy to overcome these issues because chemiluminescence has a different work mechanism (Chemically Initiated Electron Exchange Luminescence, CIEEL) which is light emission from a chemical reaction without real-time excitation, exhibiting well-performed tissue penetration and high SBR. Compared with NIR-I/II fluorescence imaging, CL imaging shows great superiorities in tissue penetration depth and SBR. All of our works are carried out for bioimaging and sensing through the modification of Schaap’s adamantylidene−dioxetane scaffold. Because Schaap’s chemiluminophores are an attractive chemiluminescent scaffold due to the relative thermal stability of dioxetane and good response-ability to detect biological markers. Doctor of Philosophy 2022-12-27T04:36:46Z 2022-12-27T04:36:46Z 2022 Thesis-Doctor of Philosophy Huang, J. (2022). Development of near-infrared chemiluminescent probes for in vivo imaging. Doctoral thesis, Nanyang Technological University, Singapore. https://hdl.handle.net/10356/163961 https://hdl.handle.net/10356/163961 10.32657/10356/163961 en This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License (CC BY-NC 4.0). application/pdf Nanyang Technological University
institution Nanyang Technological University
building NTU Library
continent Asia
country Singapore
Singapore
content_provider NTU Library
collection DR-NTU
language English
topic Science
Engineering::Chemical engineering
spellingShingle Science
Engineering::Chemical engineering
Huang, Jingsheng
Development of near-infrared chemiluminescent probes for in vivo imaging
description Molecular imaging is an indispensable tool in deciphering and monitoring the physiological and pathological processes at the subcellular or cellular level. For visualization and quantification of biological processes, multiple imaging modalities are developed along with different image-capture techniques, including ultrasound (US), computed tomography (CT), magnetic resonance (MRI), and positron emission tomography (PET) technologies. Among these different imaging modalities, optical imaging outperforms others in the high-throughput capacity, less radiative toxicity, and low-cost equipment. Moreover, in contrast to anatomical imaging and biopsy imaging, optical real-time imaging shows great advantages in time-consuming, high resolution, and noninvasiveness without pain for diagnosis and treatment in the clinic. There are two types of optical imaging agents, namely inorganic and organic imaging agents. Inorganic agents always suffer from biotoxicity resulting from leakage of metal ions and difficult biodegradability, which impede their further application in translational applications. Organic optical agents exhibit an excellent sensitivity for biomarker detection at the subcellular levels, facilitating both pre-clinical and clinical applications. Despite these merits, optical imaging is still confronted with narrow penetration tissue depth (< 1 cm) and compromised imaging quality (low signal-to-background ratio, SBR) because of tissue autofluorescence caused by real-time excitation. To address the mentioned issues, other novel imaging modalities have been developed, especially second near-infrared-II (NIR-II) fluorescence imaging and chemiluminescence (CL) imaging. NIR-II fluorescence imaging is booming along with the development of emerging NIR-II Imaging techniques in recent years. NIR-II fluorophores (emission wavelength: 1,000-1,700 nm) exhibit superior optical properties owing to diminished background autofluorescence and reduced light scattering. Unfortunately, NIR-II fluorophores always suffer from low fluorescence quantum yield and show difficulties in the design of activatable probes, causing low SBR because of the “always-on” signal. Interestingly, chemiluminescence imaging can offer another strategy to overcome these issues because chemiluminescence has a different work mechanism (Chemically Initiated Electron Exchange Luminescence, CIEEL) which is light emission from a chemical reaction without real-time excitation, exhibiting well-performed tissue penetration and high SBR. Compared with NIR-I/II fluorescence imaging, CL imaging shows great superiorities in tissue penetration depth and SBR. All of our works are carried out for bioimaging and sensing through the modification of Schaap’s adamantylidene−dioxetane scaffold. Because Schaap’s chemiluminophores are an attractive chemiluminescent scaffold due to the relative thermal stability of dioxetane and good response-ability to detect biological markers.
author2 Pu Kanyi
author_facet Pu Kanyi
Huang, Jingsheng
format Thesis-Doctor of Philosophy
author Huang, Jingsheng
author_sort Huang, Jingsheng
title Development of near-infrared chemiluminescent probes for in vivo imaging
title_short Development of near-infrared chemiluminescent probes for in vivo imaging
title_full Development of near-infrared chemiluminescent probes for in vivo imaging
title_fullStr Development of near-infrared chemiluminescent probes for in vivo imaging
title_full_unstemmed Development of near-infrared chemiluminescent probes for in vivo imaging
title_sort development of near-infrared chemiluminescent probes for in vivo imaging
publisher Nanyang Technological University
publishDate 2022
url https://hdl.handle.net/10356/163961
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