Preface

Imaging Tools for Chemical Biology is edited by Lei Feng from Dalian Medical University and Tony D. James from the University of Bath. They are pictured here (Figure 1) at the University of Bath in January 2019.

Tony D. James is a Professor at the University of Bath and Fellow of the Royal Society of Chemistry. He obtained his BSc in 1986 (University of East Anglia), PhD in 1991 (University of Victoria) and was a Postdoctoral Research Fellow in 1992–1995 (with Seiji Shinkai in Japan). He was a Royal Society Research Fellow from 1995 to 2000 (University of Birmingham).

He has been a visiting professor at Tsukuba, Osaka, Kyushu and Sophia Universities, an AMADEus invited professor at the University of Bordeaux and is a guest Professor at East China University of Science and Technology, Xiamen University, Shandong Normal University, Nanjing University, Shaanxi University of Science and Technology, Changzhou University, Zhejiang University, Qufu Normal University, Beijing University of Chemical Technology, Shanghai Normal University, Ewha Womans University, Henan Normal University, Engineering Research Centre for Hainan Bio-Smart Materials and Bio-Smart Devices, Shandong First Medical University and is a Hai-Tian (Sea-Sky) Scholar at Dalian University of Technology.

He received the Daiwa-Adrian Prize for developing scientific networks with Japan in 2013, the inaugural CASE Prize for establishing scientific networks with China in 2015, the MSMLG Czarnik Award in 2018, the Frontiers in Chemistry Diversity Award in 2020, a Royal Society Wolfson Research Merit Award (2017–2022) and is an Ewha Womans University Global Fellow. He has an h-index of 90 (ORCID 0000-0002-4095-2191) and has been listed as a Highly Cited Researcher in Chemistry by Clarivate (since 2022).

Lei Feng is a full professor at the Second Affiliated Hospital, Dalian Medical University, he received his BSc (2011) and PhD (2016) from Dalian University of Technology. His main research interest is fluorescent probes for the detection of enzyme activity. He has an h-index of 34 and serves as an associate editor for Frontiers in Chemistry (Supramolecular Section). He was awarded the “Young Elite Scientist” by the China Association of Chinese Medicine (2021) and selected for the LiaoNing Revitalization Talents Program (2023).

With this book on Imaging Tools for Chemical Biology, Feng and James have assembled a diverse selection of chapters from world-leading experts involved in developing state-of-the-art imaging systems, including: Chusen Huang; Ping Li; Bo Tang; Simon Pope; Xiao-Peng He; Sofia Pascu; Hai-Hao Han; Suying Xu; Leyu Wang; Ori Green; Minyong Li; Hua Zhang; Qinglong Qiao; Zhaochao Xu; Zhijun Chen; Sheetal Sharma; Amit Sharma; and Jong Seung Kim.

The 13 chapters contained in this book cover techniques that are currently used for bioimaging, as well as methods and approaches that are evolving and will soon become the “go-to methods” of choice for imaging applications. The areas covered in this book include near-infrared (I and II) imaging, lifetime imaging, chemiluminescence and bioluminescence imaging, photothermal imaging, super-resolution imaging, lanthanide-based imaging, AIE-based imaging, carbon dot-based imaging, multimodal (NMR and fluorescence) imaging, combined drug delivery and imaging and protein labelling.

What is apparent from these chapters is that Imaging Tools for Chemical Biology is a particularly rich and evolving area of research. Clearly the future of this area is a bright one, where limitations associated with low penetration depth, autofluorescence and low signal to noise will be addressed relatively soon. This will be achieved using longer wavelengths, lifetime-based methods, photothermal methods and multimodal systems. Coupled with these advances in improving the signal to noise and improving tissue depth penetration for analysis, super-resolution imaging will enable visualization of biological samples in greater detail. The future of many of these systems requires that they are linked with drug delivery methods (theranostics), which will ensure that disease states are tackled and treated as soon as they develop, resulting in improved patient prognosis. Within all these new techniques, the synthetic chemist will play a big role in ensuring that the de novo design and modification of existing probes are more selective for specific targets, which will involve the development of targeted fluorophores with greater selectivity, sensitivity and longer wavelengths. Going forward these synthetic methods will also evolve to use more sustainable resources, ensuring that Imaging Tools for Chemical Biology will be important for our health and the environment.

Figure 2 shows representative fluorescent molecules discussed in this book, as monitored under a microscope, for biological imaging applications.

Chusen Huang, with Qianfang Qiu, Yifei Ren and Jigao Xuan, discuss the use of near-infrared (NIR)-I bioimaging in biological applications. Given that imaging depths for NIR probes are significantly improved when compared to probes in the visible region, NIR imaging enables the accurate spatiotemporal positioning of biomolecules in vivo. In particular, NIR-I advances in bioimaging have enabled fluorescence image-guided surgery of tumors.

Ping Li and Bo Tang introduce second NIR (NIR-II, 1000–1700 nm)-based bioimaging. NIR-II bioimaging exhibits many advantages, including low photodamage, and enables deep visualization (5–20 mm) within biological samples.

Simon Pope, with Angelo J. Amoroso, introduces lanthanides for luminescent and magnetic resonance imaging (MRI). In order to stabilize Ln³⁺ complexes for use in bioimaging applications, chelating ligands are required, which include those derived from DTPA and DOTA. Complexes based on modified DTPA and DOTA ligands have been used as luminescent probes, MRI contrast agents and radiotherapeutics.

Xiao-Peng He, with Hai-Hao Han, discusses the use of super-resolution fluorescence imaging, which enables the visualization of the microstructure of cells and dynamic movements of biomolecules in real time. Super-resolution fluorescence microscopy (SRFM) facilitates the high-resolution imaging of subcellular structures, enabling a deeper understanding of the exquisitely organized structures and the interaction of biomolecules in important biological processes.

Sofia Pascu, with David Calatayud, Rory Arrowsmith, Philip Waghorn, Stanley Botchway, Stephen Faulkner and Jonathan Dilworth, cover fluorescence and phosphorescence lifetime imaging microscopies (FLIM and PLIM) in their chapter. They highlight the use of FLIM and PLIM, focusing on the detection of chemical probes within living cells, with an emphasis on metal complexes and carbon-based nanoparticles. The chapter describes how fluorescence lifetimes can be used to provide a comprehensive understanding of molecular interactions occurring in biological systems. Such advances in NIR fluorophore lifetime-based imaging will significantly advance biomedical imaging and sensing, due to deeper tissue penetration.

Hai-Hao Han, with Lei Dong, discusses the use of aggregate-induced emission (AIE) to overcome the aggregation-caused quenching (ACQ) seen with traditional fluorescence. AIE has been used to significantly enhance fluorescence bioimaging techniques, facilitating a deeper understanding of chemical biology. The chapter discusses the working mechanism of the AIE effect and applications of AIE-based fluorescence imaging in biomolecular sensing, as well as in cellular and subcellular bioimaging.

Suying Xu and Leyu Wang, with Chang Guo and Kexin Pan, introduce the concept of fluorescence and MRI for multimodal bioimaging. Combined and multimodal approaches are a very hot area in bioimaging, since by combining techniques the limitations associated with using a single technique can be overcome.

Ori Green introduces the concept of chemiluminescence for biological imaging. The chapter covers recent developments in chemiluminescence imaging tools. Two classes of chemiluminescent compounds are discussed: oxidation-dependent (such as luminol and oxalate esters) and dioxetane-based probes. In particular, dioxetane-based systems represent a significant development for chemiluminescence-based imaging, since they enable precise control of chemi-excitation, facilitating many applications in chemical biology.

Minyong Li and Zihui Huang outline advances in bioluminescent systems for biomedical applications. The bioluminescent systems developed are based on engineered luciferase and chemically modified luciferin. In particular, caged luciferin and bioluminescence resonance energy transfer (BRET) strategies have been used for the development of biosensors to illuminate physiological events.

Hua Zhang, with Jie Yuan, Hanxue Yang and Wenhui Huang, introduces photothermal imaging, photothermal conversion materials and applications of photothermal imaging. The approach relies on local temperature changes to generate biological images. The advantages of photothermal imaging include very low background and, as such, the technique is extensively used in the fields of life science, medicine, nanoscience and materials research.

Qinglong Qiao and Zhaochao Xu, with Shaowei Wu and Xiangning Fang, introduce the use of fluorogenic probes for bioimaging. Protein labelling has evolved from covalent coupling to advanced approaches, including click chemistry, genetically encoded tags and proximity labelling. Fluorogenic probes for protein labelling, have developed to enable efficient, high-resolution and wash-free imaging, facilitating the visualization of cellular functions.

Zhijun Chen, with Wei-Ming Yin, describes the use of biomass-based carbon dots (BCDs) for fluorescence bioimaging. The chapter covers recent advances of these carbon dots as a new multifunctional biomaterial. Applications of carbon dots for bioimaging are discussed and limitations and future developments are outlined.

Sheetal Sharma, Amit Sharma and Jong Seung Kim, with Jiya Mary George, Jusung An, Changyu Yoon and Dongeun Kim, have prepared a chapter on molecular-based drug delivery systems tailored for selective targeting and imaging of cancer (theranostics). The theranostic approach offers a viable alternative to conventional anticancer drugs, with potential benefits, such as cancer-selective uptake, minimal off-target toxicity and the capability of active tumor targeting. The theranostics contain a cancer-targeting unit and fluorophore reporter connected to anticancer drugs through a labile chemical linker. The incorporation of the fluorophore enables monitoring of the specific action of the drug on the target, as well as monitoring of its therapeutic response.