Near‐infrared aggregation‐induced emission materials: Bibliometric analysis and their application in biomedical field

Aggregation‐induced emission (AIE) is an intriguing photophysical phenomenon, where specific materials exhibit a remarkable surge in luminescence when brought together in non‐ideal solvents or within a solid matrix. Since the concept of AIE was first introduced in 2001, numerous advanced applications have been gradually explored across various domains, including optics, electronics, energy, and the life sciences. Of particular note is the growing interest in the application of AIE systems with near‐infrared (NIR) emissive feature in the field of biomedicine, encompassing detection, imaging, and therapeutic interventions. Notably, bibliometric analysis serves as a valuable tool to provide researchers with a comprehensive understanding of research achievements and developmental trends in specific fields, which is crucial for academic research. Herein, we present a general bibliometric overview spanning two decades of NIR‐AIE development. With the assistance of core scientific databases and various bibliometric software tools, we conducted a systematic analysis of annual publications and citations, the most influential countries/regions, leading authors, journals, and institutions, as well as the hot topics related to NIR applications and forward‐looking predictions. Furthermore, the application of AIE with NIR properties in the biomedical field is also systematically reviewed.

ultimately enhances fluorescence. [1]In 2001, Academician Ben Zhong Tang first introduced the novel concept of AIE, sparking a revolution in luminescent materials. [2]This concept initiated a research field led by Chinese scientists and was recognized by Nature as one of the four major materials in the nanophotonics revolution. [3]AIE materials, distinct from traditional organic fluorophores, exhibit excellent biocompatibility, high luminescence efficiency, good photostability, and significant Stokes shifts.This combination of properties makes them ideal for "turn-on" fluorescence detection. [4,5]AIE materials offer significant advantages in the fields of biomedicine, effectively overcoming barriers associated with traditional aggregation-caused quenching (ACQ).[15] Due to significant advancements in safety, high spatial and temporal resolution, real-time responsiveness, portability, and cost-effectiveness, NIR has emerged as one of the most powerful tools for practical applications in various domains, particularly in the biomedical field.It fulfills the demand for non-invasive, deep-penetrating, and minimally disruptive techniques in biological research.In recent years, there has been great progress in transitioning from traditional NIR technologies to novel NIR materials, particularly in the areas of biological imaging, biosensing, and multifunctional diagnostics.18] Interdisciplinary frontiers have the ability to build bridges between different disciplines, facilitating the attainment of groundbreaking outcomes. [19][22] It's an innovative discipline that extracts mathematical principles from an extensive body of literature.It not only assesses the contributions of countries/regions, authors, journals, and institutions but also reveals the hotspots and development trends in specific research areas.Over the past 20 years, numerous research papers and reviews have been published, but there has been limited analysis and investigation of the existing research using bibliometric analysis.
Here, based on the data collected from the Science Citation Index, we have conducted a literature overview and analysis of the research of NIR-AIE in the biomedical field.Using several bibliometric software tools, the annual growth rate, the most productive countries, major contributors, prominent journals and institutions are displayed and visualized.By the analysis of citation order and keyword co-occurrence, the research hotspots in the field of NIR-AIE is revealed.Furthermore, the preparation of NIR-AIE materials and their applications in biology are systematically reviewed.Lastly, it outlines current challenges and potential future directions in the NIR-AIE field.

Data source and methods
A literature retrieval was conducted on the WoSCC database on Aug 21, 2023, for all articles and reviews related NIR-AIE from 2008 to 2023, using the following search formula: (TI = (aggregation-induced emission) AND TI = ("near infrared" or near-infrared)) OR (AK = (aggregation-induced emission) AND AK = ("near infrared" or near-infrared)) OR (AB = (aggregation-induced emission) AND AB = ("near infrared" or near-infrared)).Only English language publications were considered for the analysis process.VOSviewer (version 1.6.19), citespace, and bibliometrc.comwere used to conduct data mining and analysis on objects such as countries, institutions, authors, keywords, journals, related diseases, and association methods, visualizing the overall trends, distribution, and hotspot changes in this field.

Quantitative analysis of publications
We searched for a total of 518 papers, with 481 articles and 37 reviews included in our subsequent analysis.It involves 27 countries, 401 organizations, 2591 authors, and 133 journals.Figure 1A presents the trend of annual publication output by different countries.It is evident that from 2008 to 2015, there was an exploratory phase in the field of NIR-AIE, with annual publication not exceeding 20.Since 2016, the annual publication rate of NIR-AIE research has been steadily increasing, reaching a peak of 106 in 2021.China significantly outpaces other countries in terms of publication numbers, indicating China has the highest research activity in this field.

Countries and institutions
In 2016, AIE materials were recognized by the journal Nature as one of the four leading nanomaterials supporting the "nano-revolution", marking a rare instance of a novel material originating from Chinese scientist.The research on AIE materials has expanded from China to the global stage.These publications came from 27 countries and 401 institutions.It can be seen that the country with the most publications is China (Asia), followed by the republic of Singapore (Asia) and United States (North America) (Figure 1B).China's publication quantity far exceeds that of the republic of Singapore and other countries.Notably, there is a lot of active cooperation between different countries, especially between China and the republic of Singapore, China and the United State (Figure 1C).Subsequently, based on the minimum number of publications of 7, 34 institutions were selected for visual analysis, and a collaborative network was constructed.As shown in Figure 1D, it can be seen that all the top ten organizations are located in China.The top five organizations with the most publications are the Hong Kong University of Science and Technology (n = 87), South China University of Technology (n = 66), Shenzhen University (n = 58), the Chinese University of Hong Kong (n = 53), and Zhejiang University (n = 45).The cooperation between Hong Kong University of Science & Technology, South China University of Technology, and Shenzhen University is very close.

Journals and co-cited journals
Publications related to NIR-AIE were published in 133 journals.The journal with the highest impact factor (IF) among the top ten in terms of publication volume is "Advanced Materials", followed by "Advanced Functional Materials" and "ACS Nano".30 journals were selected based on the minimum number of relevant publications equal to 5 and plotted the journal network (Figure 2A). Figure 2A shows that "Advanced Materials" has active citation relationships with "ACS Nano, Advanced Functional Materials" etc.As shown in Table 1, among the top 10 co-cited journals, 6 journals were cited more than 1000 times, and "Advanced Materials" was the most co-cited journal, followed by "Advanced Functional Materials and Angewandte Chemie-International Edition".Journals with the minimum co-citation equal to 100 were filtered to map the co-citation network (Figure 2B)."Angewandte Chemie-International Edition, Advanced Materials, Journal of the American Chemical Society, and Chemical Communications" all have a positive co-citation relationship with each other.By analyzing the relationship between citing and cited journals, we gain insights into the flow of knowledge at the journal level, providing an intuitive reflection of research trends in the field.Serving as a universal platform for collective scientific exploration, NIR-AIE continually integrates with other research areas such as materials, biology, energy, and the environment, injecting new vitality into these fields.

Authors and co-cited authors
A total of 2591 authors participated in the study of NIR-AIE.Table 2 shows the top 10 authors and co-cited authors.Among the top 10 authors, each published more than 10 papers.Ben Zhong Tang is the author with the highest number of published articles and the most citations.Then a collaborative network based on authors whose number of published papers is more than or equal to 7 (Figure 3A).The top three authors with the largest node are Ben Zhong Tang from the Chinese University of Hong Kong, Dong Wang from Shenzhen University, and Jacky WY Lam from the Hong Kong University of Science and Technology.Close collaboration among multiple authors were observed.Table 2 also shows the top 10 co-cited authors, while selecting 46 authors (with a minimum co-cited times of 50) and drawing a co-cited network diagram (Figure 3B).The most co-cited author is Ju Mei (n = 320), followed by Ji Qi (n = 225) and Yuning Hong (n = 193).There are also active collaborations among different co-cited authors.

Citation and co-cited references
Citation and Co-cited literatures refer to references that have been cited and co-cited by multiple other publications, therefore they can be regarded as the foundation of research in a certain field.A total of 518 citation references for the study of NIR-AIE from 2008 to 2023.According to the minimum citation index of 100, a total of 52 literature were selected and a citation network diagram was drawn (Figure 3C).The literature with the most citations is "Li (2019), Chem.Soc.Rev., 2019, 48, 38-71", which reported "Development of organic semiconducting materials for deep-tissue optical imaging, phototherapy and photoactivation", with a total of 761 citations.According to the minimum co-citation index of 30, a total of 38 literature were selected and a co-citation network diagram was drawn (Figure 3D), and the top 10 cocited references were shown (Table 3).The literature with the most citations is "mei j, 2015, chem rev, v115, p11718", which reported "Aggregation-Induced Emission: Together We Shine, United We Soar!", with a total of 214 citations.

Hotspots and frontiers
The research hotspots and frontiers of NIR-AIE were identified through co-occurrence analysis of keywords.We filtered keywords with the number of occurrences more than or equal to 10 and mapped the keywords network (Figure 4A)."Aggregation-induced emission", "fluorescence", "photodynamic therapy", "red", "cancer", "probes", "therapy", "cells", "intramolecular charge-transfer", and "photosensitizers" are the top ten high-frequency keywords appearing in this field, representing the main research direction of NIR-AIE.Building upon the keyword co-occurrence network, we further conducted keyword clustering analysis using the Latent Semantic Indexing (LSI) algorithm, as shown in Figure 4B.
The detection of burst keywords helps reveal the transition of research hotspots across different time periods, aiding in the assessment of potential development trends and cutting-edge investigations.In the context of this study, "begin" and "end" indicate the commencement and conclusion times of burst keywords, while "strength" reflects the burst keyword's intensity, with higher values signifying greater influence.Burst keyword detection was conducted on the literature keywords, with a γ parameter set to 0.6 and a minimum duration of 2, resulting in 25 burst keywords, as depicted in Figure 5. Initially, the central emphasis of AIE research was on light-emitting diodes and organic nanoparticles, which continued as a prominent research hotspot until 2019.From 2012 onwards, AIE gradually expanded into the biomedical field.After 2018, there was a noticeable transition towards exploring near-infrared luminescence, photodynamic therapy, mitochondria, and related areas.
The AIE phenomenon holds extensive application prospects in various research fields.NIR-AIE, due to its outstanding optical performance, particularly excels in the field of medical diagnostics and treatment.As evident from the above analysis, NIR-AIE has been highly active in recent years in areas such as photodynamic therapy and in vivo tracking.Therefore, we will provide a review of the application of NIR-AIE in the biomedical field based on the above analysis directions.

NIR-AIE MATERIALS
After more than 20 years of development, AIE materials have undergone significant advancement and the types are constantly expanding.The basic unit of AIE, known as AIEgens, plays a crucial role in the construction of AIE materials.These materials have evolved from pure hydrocarbons to heteroatom-containing compounds, from small molecules to large molecules, and from organic to inorganic or metal organic compounds.Although AIE materials typically possess high PLQY.However, due to their highly distorted structure, the conjugation of these molecules is greatly reduced.Therefore, its molar extinction coefficient (MEC) is usually relatively small, which is not conducive to achieving optimal luminous brightness. [23]29][30][31][32][33][34][35][36][37][38][39][40] For fluorophores that tend to show aggregationinduced quenching, such as fluorescein, boron difluoride dipyrromethene, and naphthalimide, they can also exhibit aggregation-induced emission by connecting components with AIE features.This serves as a general strategy for constructing novel AIE molecules.Compared to visible light molecules, NIR molecules have a lower energy gap.Reducing the energy gap (Eg) is an effective approach in designing NIR fluorescent molecules.According to molecular orbital theory, extending the π-conjugation length can elevate the energy level of the highest occupied molecular orbital (HOMO) and lower the energy level of the lowest unoccupied molecular orbital (LUMO), thus significantly reducing the energy gap.In addition, modification of conjugated systems with electron-donating and electron-accepting groups can also adjust the molecular Eg.Based on these principles, there are several strategies for constructing NIR-AIE materials, including side-chain engineering, polymerization, twisted intramolecular charge transfer mechanism, donor (D)-acceptor (A) structure, and extended conjugation length strategy. [41]For example, for conjugated acceptors with strong electron-withdrawing properties, such as pyrrolo [3,4c]pyrrole, benzothiadiazole etc., which have a symmetric structure and modification sites on both sides, introducing electron donors at both ends of their skeleton can be an effective method to construct donor-acceptor-donor (D-A-D) featured conjugated molecules. [42]This represents an effective strategy for constructing near-infrared fluorescent materials, as adopted in most NIR-AIE constructions illustrated in Figure 6.Miao et al. [43] pioneered the development of the first NIR fluorescent sensor, DBHM, with AIE properties for sensing.They employed triphenylamine as the donor and acrylonitrile as the acceptor, forming a D-π-A structure.The π-conjugated bridge, composed of a benzene ring and a C═N bond, effectively binds with Cu 2+ , resulting in enhanced AIE characteristics and recognition in the NIR region.The intramolecular charge transfer effect (CT) significantly influences the fluorescence of D-A type molecules.When the electron-donating capability of the electron donor in the fluorescent molecule is weak, fluorescence is primarily emitted through intramolecular CT.Conversely, when the electron donor in the fluorescent molecule has a strong electron-donating capability, fluorescence is predominantly emitted through excitation.Additionally, the connection mode between the electron donor and acceptor in the fluorescent molecule structure also plays a crucial role in determining spectral properties.Table 4 summarizes the optical information of NIR-AIE materials developed in recent years.
The benzothiadiazole (BTD) group, as a crucial electron acceptor, is widely employed in the design of red/NIR luminescent materials. [44]Simply replacing the sulfur atom in the molecular structure of BTD with a selenium atom results in a more polar benzothiadiazole derivative known as benzoselenadiazole (BSD).This modification is more favorable for promoting intramolecular charge transfer, leading to enhanced absorption and emission in longer wavelength regions, thereby opening up an optical window for biological research (>650 nm).Qian and Tang [45] collaborated to design and synthesize a selenium-containing deep red/NIR dye TTSe based on AIE (Figure 6B).TTSe can be easily formulated into nanoparticles, retaining AIE properties.These nanoparticles exhibit remarkable brightness, significant Stokes shift, excellent biocompatibility, and outstanding photostability.Recently, Tang et al. [46] reported a novel second near-infrared (NIR-II) AIE polymer construction strategy based on block copolymerization, which can precisely control the proportion of planar and twisted units in the polymer main chain through molecular engineering, thereby preparing a new type of semiconductor polymer with balanced absorption performance and fluorescence quantum efficiency.This work is based on a ternary copolymerization strategy, using D-A-D twisted structural units with ortho alkyl side chains (T1-BBTD-T1) and D-A-D planar structural units with meta-alkyl side chains (T2-BBTD-T2) as comonomers, and conducting random copolymerization with tetraphenylethylene substituted phenothiazine derivatives to prepare a series of SPs (Figure 6C).This strategy can precisely control the proportion of planar and twisted block units in the polymer main chain by adjusting the feed ratio of two monomers without the need for tedious pre synthesis of complex Janus monomers, thus achieving flexible and convenient regulation of the photophysical and photothermal properties of NIR-II SPs.
49][50] Compared to individual dye molecules, the J-aggregates exhibit red-shifted absorption and emission spectra. [51]herefore, constructing organic dye J-aggregates can be used as a strategy to obtain fluorescent groups with NIR-F I G U R E 6 (A) Several commonly used AIE building units.(B) The molecular structure of TTSe.Reproduced with permission: Copyright 2019, Royal Society of Chemistry. [45](C) Synthesis and chemical structures of polymers SP1 to SP5.Reproduced with permission: Copyright 2023, American Association for the Advancement of Science. [46](D) Theoretical simulations of BT3 and BT6 molecules.Reproduced with permission: Copyright 2023, Wiley-VCH. [52]E) Synthetic pathway of TVP and NIR-AIEgen TTVP.Reproduced with permission: Copyright 2018, Royal Society of Chemistry. [60] emission.Lee et al. [52] has developed a high-brightness NIR-II J-aggregate based on benzo[c]thiophene (BT) for bioimaging and optical therapy (Figure 6D).Based on the previously reported NIR phototherapy molecule, BT3, [53] the research team effectively regulated the absorption and emission properties of BT6 molecules by extending the electron-donor (D) and enhancing the distortion between the donor and acceptor (D-A).The BT6 dye exhibits distinct J-aggregation characteristics when encapsulated with amphiphilic polymers to form water-soluble nanoparticles (NPs).Compared with the individual molecular state, the absorption and fluorescence of the NPs aggregates demonstrate redshift properties.Moreover, the Stokes shift of BT6 extends to 402 nm, effectively suppressing fluorescence selfabsorption.Furthermore, the fluorescence intensity of BT6 dye significantly increases after the formation of aggregates, displaying a unique AIE phenomenon.The aforementioned strategy represents a classic approach to obtaining NIR-AIE, but it is prone to fluorescence quenching due to factors such as strong π-π stacking or twisted intramolecular  ) and easily obtainable diarylamine derivatives.The synthesis strategy involves the direct coupling of aromatic secondary amines with BT-2Br through the Buchwald-Hartwig coupling reaction, resulting in structurally simplified symmetric molecules. [54]ater solubility is a critical evaluation criterion for fluorescent materials used in biological applications, as it directly affects the biocompatibility, detection sensitivity, and target specificity of the material. [55,56]Small molecule water-soluble AIEgens, with advantages such as clear structure, ease of use, well-defined pharmacokinetics, and tunable chemical structure, demonstrate high potential for clinical applications.However, for AIEgens with NIR fluorescence emission, their intrinsic hydrophobic nature makes the synthesis of small molecule NIR-AIEgens with excellent water solubility challenging.[59] Tang et al. [60] first reported water-soluble AIEgen in 2017, named TTVP, which has the largest NIR emission wavelength.TTVP can specifically target cell membranes for rapid fluorescence staining, allowing for clear imaging without the need for elution.In addition, TTVP has photodynamic properties and can kill cancer cells under visible light irradiation.The molecular structure of TTVP contains triphenylamine fragments (D) or/and thiophene fragments (D and π-bridges), C═C (π bridges), and pyridine salt fragments (A) (Figure 6E).The incorporation of hydrophilic pyridine salt and ammonium salt fragments imparts excellent water solubility to both TVP and TTVP molecules.Tang and his colleagues [61] pointed out that NIR-AIEgens can modify functional groups including positively and negatively charged groups, non-ionic hydrophilic chains, and bioactive groups to improve their water solubility.

Biosensing
With the rapid development of medicine, life science research is gradually shifting towards the molecular level.The emergence of AIE biomaterials provides an effective and promising tool for disease detection and diagnosis. [72,73]he luminescent mechanism of AIE can be summarized as restriction of intramolecular motion (RIM), including restriction of intramolecular rotation (RIR) and restriction of intramolecular vibration (RIV). [74][77][78] Especially, NIR-AIE demonstrates a higher signal-to-noise ratio and amplification effect, providing it with excellent responsiveness and specificity to changes in the microenvironment.By introducing water-soluble functional groups or specific recognition moieties, the unique luminescent properties of NIR-AIE can enable "light-up" label-free detection of various ions and biomacromolecules.As a biosensing reagent, it is essential for the NIR-AIE material to selectively bind to target biomolecules or cells to achieve precise detection of specific biological processes or pathological conditions.Furthermore, within a biological environment, NIR-AIE materials must maintain stability, unaffected by factors such as bodily fluids, enzymes, temperature etc., and sustain their performance over extended periods.81] 4.1.1

Microbial pathogens
Microbial pathogens, including bacteria, fungi, and viruses, pose significant threats to global public health.In clinical practice, early diagnosis and precise treatment are crucial for reducing the mortality rate of these pathogens infections.[84][85][86][87] Li et al. [88] proposed a lateral flow immunoassay method based on AIE 810 NP for early detection of IgM and IgG against SARS-CoV-2 during the seroconversion window period (Figure 7A).This method can detect IgM and IgG against SARS-CoV-2 within 1-7 days after symptoms appear, which is earlier than commercial test strips based on AuNPs (typically 8-15 days).Therefore, the lateral flow immunoassay based on AIE 810 NP can serve as an alternative method for early detection of SARS-CoV-2 IgM and IgG.Moreover, it holds significant potential for clinical diagnosis not only for SARS-CoV-2 but also for other viruses.

Tissue
Liver, as the primary organ for drug metabolism and detoxification, is susceptible to damage and its function can be severely impaired.Therefore, in situ diagnosis and realtime monitoring of liver injury are of significant importance.Zhang et al. [71] firstly introduced an AIE probe, called DPXBI, which emits in the NIR-II for early diagnosis of liver injury.The strong electron donor-acceptor interactions and extended π-conjugation promote intramolecular charge transfer.Simultaneously, diphenylxanthine serves not only as an electron donor but also functions as a molecular rotor.Due to the conformational distortion in the diphenylxanthine segment, DPXBI reduces intermolecular π-π stacking, deducing fluorescence quenching during the formation of aggregates.DPXBI has strong intramolecular rotation, excellent water solubility, and chemical stability.By modulating the NIR-II fluorescence intensity, it demonstrates strong sensitivity to viscosity changes and can achieve rapid response and high selectivity.The remarkable viscosity responsive properties of DPXBI allow for accurate monitoring of drug-induced liver injury (DILI) and hepatic ischemia-reperfusion injury (HIRI), with good image contrast against the background (Figure 7B).By employing this approach, liver injury detection in a mouse model can be advanced by several hours compared to typical clinical tests.

Cell
Understanding the mechanisms and advancements of neutrophil related diseases, such as acute inflammation, is crucial.Ding et al. [89] reported the use of distorted molecular geometries to amplify the activation of NIR afterglow luminescence for studying neutrophil related diseases.They designed and synthesized a dual-responsive afterglow luminescent nanoprobe for peroxynitrite (ONOO − ) and pH (Figure 7C).Under physiological pH conditions and in the presence of ONOO − , the nanoprobe exhibits activated NIR afterglow luminescence.By introducing AIE with distorted molecular geometries into the system, its intensity and duration can be greatly enhanced.In vivo studies, it has demonstrated that this nanoprobes can sensitively reveal the development of acute skin inflammation by using three disease animal models.It can detect the initial neutrophil infiltration and the onset of acidification, distinguishing between allergies and inflammation rapidly.Furthermore, it can be used to quickly screen anti-tumor drugs capable of inducing immunogenic cell death.

Biomolecule
The occurrence of certain diseases is often accompanied by the abnormal expression of biomolecules. [90]93] The abnormal expression of CO gas can lead to conditions like hypertension and heart failure. [94,95][98] Alpha fetoprotein levels have been used for the diagnosis of hepatocellular carcinoma. [99]The level of procalcitonin can be used as an early diagnostic indicator for bacterial infections. [100]The detection of creatine kinase isoenzyme levels is crucial for the evaluation of myocardial infarction. [101]Protein aggregation is closely associated with over 50 human diseases and can be categorized into two main classes: amyloid fibers with typical β-sheet structures and amorphous aggregates lacking regular morphology.Fluorescent probes with AIE properties have a "turn-on" feature, excellent optical properties, and overcome the limitations of traditional probes.They have been successfully applied to detect amyloid fibers or amorphous aggregates.Quan et al. [102] successfully applied QM-FN-SO 3 fluorescent probe that they previously designed for detection of amorphous protein aggregates.In vitro, the QM-FN-SO 3 probe allows for the quantitative detection of amyloid fibers and amorphous aggregates through NIR fluorescence signals, and can track their aggregation kinetics in real time (Figure 7D).In vivo, it can penetrate the outer and inner membranes of bacteria (Escherichia coli), allowing the detection of protein aggregates in the bacterial cell periplasm or cytoplasm.Furthermore, the probe can also penetrate the membranes of HEK-293T cells, enabling the detection of protein aggregates in both the cytoplasm and nucleus.Real-time and accurate early detection of β-amyloid protein (Aβ) deposition in situ is crucial for the diagnosis and timely intervention of Alzheimer's disease (AD).Mei's team [66] used readily available and cost-effective materials to synthesize a rod-shaped, amphiphilic red/NIR emitting AIEgen called AIE-CNPγ-AD.This probe combines the preferred geometric configuration of Aβ deposition, amphiphilic molecular structure, extended Dπ-A electronic structure, and 3D conformation.It achieves high signal-to-noise ratio, high-contrast imaging, and precise tracking of Aβ deposition in AD mouse model in vivo (Figure 7E).

Bioimaging
The vigorous development of biomedical imaging technologies has provided a powerful new tool for clinical  [71] (C) A dual-responsive afterglow luminescent nanoprobe for ONOO − and pH.Reproduced with permission: Copyright 2022, American Chemical Society. [89](D) Detection of aggregates via the NIR AIE-active probe, QM-FN-SO 3 .(d1) QM-FN-SO 3 structure.(d2) Schematic illustrations of the applications of the QM-FN-SO 3 probe in detecting amorphous aggregates, amyloid fibers, and chaperone activity.Reproduced with permission: Copyright 2023, Wiley. [102](E) Diagram showcasing the in-vivo imaging process of Aβ deposits using AIE-CNPγ-AD in brains of AD model mice, and the potential of AIE-CNPγ-AD in early diagnosis of AD.Reproduced with permission: Copyright 2022, Springer. [66]agnostics.Although traditional imaging techniques such as ultrasound and computed tomography have advanced rapidly, they are limited by harmful radiation exposure, low spatiotemporal resolution, poor sensitivity, and the inability to provide real-time and in situ evaluation. [103,104][107][108][109] Many traditional AIE have been widely used for research, most of which emit in the visible light range (400-700 nm).However, its limited tissue penetration depth hinders accurate imaging of deeper tissues, posing an obstacle to clinical translation.Therefore, AIE materials that emit visible light have been primarily applied to extracellular biological imaging such as cell imaging and bacterial imaging.[112] Additionally, it reduces the damage of light to biological tissues and is particularly suitable for in vivo imaging and imaging guided therapy. [113,114][117] They hold promise for various in vivo imaging applications, including vascular imaging, [118] lymphatic imaging, [119] sentinel lymph node localization, [120] and image-guided surgery. [121][124] To promote NIR-AIE materials as deep optical contrast agents in clinical practice, in addition to requiring stronger fluorescence brightness and longer emission wavelengths, they also need to have good biocompatibility and stability in the biological environment.This section introduces the applications of NIR-AIE materials in various aspects of biological imaging, including biomolecules, subcellular organelles, tissues, living organisms, and pathogens.In addition to traditional single-photon fluorescence imaging, it also includes novel imaging techniques such as two/three-photon imaging, phosphorescence imaging, and afterglow imaging.NIR-AIE based biological imaging has become a crucial tool for understanding life processes, contributing to the further development of diagnostic and therapeutic approaches.

Biomarker molecule
High fidelity imaging of amyloid-β (Aβ) plaques is crucial for the early detection of Alzheimer's disease.However, it has been demonstrated that commercially available thioflavinderived compounds (ThT or ThS) exhibit significant ACQ effects, low signal-to-noise ratios (S/N), and limited bloodbrain barrier (BBB) penetration, which severely restricts the in vivo detection of Aβ plaques.Zhu et al. [125] employed a rational "step-by-step" molecular design strategy to address the inherent drawbacks of the commercial dye ThT.They extended the wavelength range to the NIR region by introducing lipophilic π-conjugated thiophene bridges.Furthermore, by altering the substitution position of the hydrophilic sulfonate groups, they ensured specific hydrophilicity to keep the molecule in a dispersed state before binding to Aβ deposits.This guarantees that the AIE probe maintains fluorescence off status before binding to Aβ plaques.The NIR probe QM-FN-SO 3 effectively addresses the requirements of lipophilicity for longer emission and the aggregation behavior from water to protein fibril formation (Figure 8A).

Subcellular organelle
Over the past two decades, fluorescence imaging techniques based on AIE have garnered significant attention due to their superiority in overcoming technical challenges.As a result, AIE-active bioprobes with subcellular targeting capabilities have been extensively studied for visualizing subcellular structures and monitoring biological processes. [126]Mitochondria are the central hub for cellular energy metabolism, featuring a highly dynamic structure.[129][130] Zhu et al. [131] reported a NIR-AIE probe targeting mitochondria, which can perform high fidelity spatiotemporal imaging of these organelles (Figure 8B).Commercially available mitochondrial probes such as MTG and MTR have inherent drawbacks, including ACQ effects and poor photostability.These limitations prevent them from accurately reflecting the dynamic changes in mitochondria.The team creatively developed a new AIE-based fluorescent unit called TCM.Through rational molecular structure design, they combined AIE unit with lipophilic targeting group TPP cation to create controllable aggregation states and matching charge densities.They successfully solved the challenge of balancing hydrophilicity and fluorescence activation properties in mitochondrial-targeted AIE probes, achieving high signal-to-noise ratio and highfidelity spatiotemporal imaging of mitochondria.Notably, compared to commercial probes like MTG and MTR, TCM-1 exhibits excellent photostability and concentration independent targeting ability.TCM-1 has the potential to replace commercial probes such as Mitotracker Green FM or Mitotracker Red FM.Lipid droplets (LDs) play an essential role not only in lipid metabolism and energy storage but also in regulating processes such as protein degradation, maintaining membrane homeostasis, and cell signal transduction. [132,133]LDs are typically believed to originate from the endoplasmic reticulum and further distributed into the cytoplasm.However, research has revealed that there is a certain number of LDs present in the nucleus of liver cells.These nuclear LDs originate from lipid precursor proteins and accumulate significantly within the inner nuclear membrane during endoplasmic reticulum stress.BODIPY 493/503 is currently the only reported small-molecule fluorescent probe for nuclear LDs imaging.However, due to its ACQ properties, it is prone to self-quenching during aggregation, leading to high fluorescence background, poor photostability, and low signal-to-noise ratio. [134]Chen and his colleagues [67] have developed a novel lipid droplet targeted NIR-AIE fluorescent probe called DTZ-TPA-DCN, which can be used for super-resolution fluorescence imaging of LDs and dynamic monitoring of nuclear LDs.DTZ-TPA-DCN exhibits a maximum absorption peak at 495 nm and a maximum emission peak at 715 nm, displaying distinct AIE properties.In addition to labeling cytoplasmic LDs, DTZ-TPA-DCN can be used for the dynamic monitoring of nuclear LDs during endoplasmic reticulum stress (Figure 8C).
The plasma membrane is a crucial barrier that separates the internal and external environments of a cell.It plays a key role in cellular processes such as cell migration, diffusion, endocytosis, exocytosis, and transmembrane transport of substances.The integrity of the plasma membrane is directly related to the overall integrity of biological cells, and structural abnormalities are closely associated with cell aging, apoptosis, and certain physiological diseases.Therefore, long-term and in-situ tracking and imaging of The "step-by-step" approach to address the inherent limitations of ThT and create highly sensitive off−on NIR probes.Reproduced with permission: Copyright 2019, American Chemical Society. [125] Copyright 2021, Royal Society of Chemistry. [67](D) Diagram outlining the design principles of membrane probes with ultrahigh specificity and prolonged imaging capabilities.Reproduced with permission: Copyright 2023, Royal Society of Chemistry. [135](E) Marking of myelin sheath in teased sciatic nerve fibers employing PM-ML.(e1) Schematic depiction of an axon in the sciatic nerve myelinated by Schwann cells.(e2) Confocal image of sciatic nerve fibers post-fixation.(e3) A section of teased sciatic nerve fibers.Reproduced with permission: Copyright 2021, National Academy of Sciences. [137](F) Schematic of fabrication procedure and application scenarios of BPN-BBTD@F127 NPs.Reproduced with permission: Copyright 2021, Wiley-VCH. [142](G) Schematic illustrations.(g1) PEGylation of AIE dots, (g2) NIR-IIb fluorescence uterine angiography, (g3) NIR-IIb fluorescence uterine hysterography and (g4) the main uterine disease models.Reproduced with permission: Copyright 2021, Elsevier. [69](H) A NIR-II nanoprobe based on AIEgen (BBT-C6T-DPA-OMe NPs) for blood circulation assessment.Reproduced with permission: Copyright 2023, American Chemical Society. [143]he plasma membrane is of great significant.Although the first-generation plasma membrane probes based on AIEgen exhibited good photostability and wash-free capability.But their solubility in water is poor, resulting in a lack of imaging integrity and membrane specificity.Qian et al. [135] designed an AIE active molecular probe APMem-1 with NIR emission.It has demonstrated that APMem-1 could provide high contrast and specific imaging of plant cells, even after 10 h.In addition, the author confirmed the universal applicability of the probe to different cell types and plants, and verified the effectiveness of multi strategy collaboration in the plasma membrane probe and the universality of APMem-1 (Figure 8D).

Tissue
][138] Chen et al. [137] have developed a NIR fluorescent probe (PM-ML) with AIE properties and plasma membrane targeting capabilities, designed for high selectivity and high signal-to-noise ratio imaging of myelin sheaths.
The authors selected a molecular framework with a typical D-π-A (donor-π-acceptor) structure and introduced bithiophene units between the electron donor and the double bond.
The electron donor and π-conjugated system possess strong hydrophobicity, allowing them to embed into the nonpolar tails of phospholipids.The hydrophilic electron donating pyridinium salt carries positive charges and can interact electrostatically with the negatively charged phospholipid heads to achieve plasma membrane targeting.Compared with commercial myelin sheath probes like fluoromyelin Green/Red and DiD, PM-ML can specifically label and image myelinated nerve fibers in sciatic nerve and mouse brain tissue with high signal-to-noise ratio (Figure 8E).It is compatible with various optical transparency processing methods for brain tissue and maintains excellent fluorescence intensity and selectivity in three-dimensional fluorescence imaging and long-term storage.
Cancer is a globally prevalent and highly lethal disease.Surgical resection remains the most effective clinical treatment method to date.However, for invasive or metastatic cancers, the tumor boundaries may be extremely unclear, and tumor cells may infiltrate surrounding vital tissues and organs.In such cases, even experienced surgeons may not be able to completely remove the tumor, leaving behind a small amount of residual cancer cells.Therefore, achieving precise intraoperative detection and complete removal of residual tiny lesions is crucial for cancer treatment.Intraoperative fluorescence guidance allows surgeons to better identify the location of lesions, as fluorescent probes not only aid in rapidly locating the site of the disease but also enable the visualization of normal tissues. [139,140]u et al. [141] found that intraoperative NIR-II imaging provides higher sensitivity for tumor detection, higher tumor-to-background signal ratio, and increased detection rate.Lin et al. [142] encapsulated a NIR-II AIE nanoprobes (BPN-BBTD nanoparticles).Additionally, for the first time, the author performed NIR-II fluorescence imaging guided intestinal segment resection in a dextran sulfate sodium (DSS)-induced mouse model of inflammatory bowel disease (IBD).NIR-II fluorescence imaging helps rapidly locate severely affected intestinal segments and ensure complete resection.To understand the distribution of BPN-BBTD nanoparticles in the intestinal wall, a self-made NIR-II fluorescence wide-field microscope was used.It was found that the nanoparticles mainly accumulated in the mucosa and submucosa (Figure 8F).In the NIR-II spectral range, compared to NIR-IIa (1300-1400 nm) fluorophores, NIR-IIb (1500-1700 nm) fluorescence exhibits smaller scattering and greater tissue absorption.This wavelength range has minimal autofluorescence, providing deeper tissue penetration and higher spatial resolution in in vivo imaging.Zhang et al. [69] successfully utilized AIE probes (OTPA-BBT dots) to visualize the physiological state and uterine peristalsis of the uterine cavity in real-time.It can also diagnose various uterine conditions, such as uterine perforation and malformations (Figure 8G).The circulatory system plays a crucial role in maintaining the physiological function of animal organs.Dysfunction of the circulatory system can directly cause hemodynamic abnormalities, leading to poor organ perfusion and related diseases.Tang et al. [143] developed a NIR-II nanoprobe based on AIEgen (BBT-C6T-DPA-OMe NPs) for accurate assessment of blood circulation (Figure 8H).Compared with commercially available ICG dyes, BBT-C6T-DPA-OMe NPs have a longer absorption wavelength, higher NIR-II brightness, greater photostability, and a wider optimal imaging window (t 1/2 = 16.25 h).After intravenous injection of BBT-C6T-DPA-OMe NPs, a small vessel system with a diameter of ∼55 µm can be observed through high spatial resolution imaging of the hindlimbs in vivo.Moreover, high frame rate (HFR) dynamic imaging successfully assessed deep organ perfusion in peripheral arterial disease (PAD), monitored vital signs, and accurately evaluated vascular hemodynamics.Importantly, a linear relationship between fluorescence signal intensity and blood flow velocity is established, allowing for direct assessment of hemodynamics based on changes in fluorescence intensity in blood flow.The Qian's research group [144] proposed a design strategy for long-chain biocompatible AIE probes for excretion in biological courses.They pioneered the application of AIE probes for transcranial NIR imaging of cerebral vasculature and NIR IIb imaging of the gastrointestinal tract in non-human primates.The imaging depth reached nearly 700 µm intracranially, surpassing the capabilities of typical AIE materials.
Iatrogenic ureteral injury is one of the most serious complications in abdominal and pelvic surgeries.Real-time identification of the ureter during surgery is crucial for preventing iatrogenic ureteral injury and treating ureteral-related diseases.Currently, clinical techniques used to identify the ureter include spontaneous ureteral peristalsis, Kelly's sign, stent placement, and intravenous injection of methylene blue.However, their effectiveness in preventing ureteral injury is limited.Tang's team [145] reported a method using NIR-II nanoparticles (2TT-oC6B dots), which can perform fluorescence imaging of the ureter during surgery in rabbits.These 2TT-oC6B dots are composed of AIEgens and a DSPE-PEG2000 shell approved by the FDA.Its emission peak is located at 1030 nm, with a high fluorescence quantum yield of 11.0%.The signal-to-background ratio and penetration depth of fluorescence imaging of 2TT-oC6B dots in the ureter are significantly superior to ICG.After retrograde injection of 2TT-oC6B dots into the ureter, precise localization of ureteral injuries or diseases was consistently achieved through NIR-II fluorescence signals.Additionally, the patency of the repaired ureter can also be evaluated by injecting 2TT-oC6B dots.This information indicates that 2TT-oC6B dots have specific fluorescence properties and NIR-II imaging capabilities, providing a promising method for identifying and evaluating ureteral conditions and injuries during surgery.
So far, AIE materials have not entered clinical applications.One of the main reasons is the lack of systematic evaluation of the toxicity of AIE materials and in-depth research on their imaging performance.Non-human primates have a close evolutionary relationship with humans, providing an excellent animal model for the clinical translation of AIE probes.Tang, along with Zheng and Li, [146] conducted pioneering research on the acute toxicity of AIE probes in non-human primates.They achieved NIR-II fluorescence imaging of blood vessels in the axillary region at a depth of 1.5 cm, which is of great significance for promoting the clinical application of NIR-II fluorescence imaging.Zhou et al. [147] provided a comprehensive and multi-faceted example of optical imaging-guided surgical procedures using AIE luminescent agents, ranging from small animals such as mice and rabbits to typical nonhuman primate models such as macaques.Folic-AIEgen can not only generate strong and stable fluorescence for the examination and surgical resection of sentinel lymph nodes (SLNs), but also provide imaging and guidance for precise resection of metastatic tumors with superior tumor/normal tissue ratio and rapid tumor aggregation.

Multimodal imaging
Molecular imaging has evolved into a versatile tool for understanding various biological molecules and visualizing fundamental biological processes.Different molecular imaging modalities have been developed to achieve these objectives, including fluorescence imaging (FI), magnetic resonance imaging (MRI), positron emission tomography (PET), ultrasound imaging, computed tomography (CT), photoacoustic imaging (PAI), and more.Each imaging modality possesses unique advantages and inherent limitations in terms of sensitivity, spatial resolution, and tissue penetration depth.For instance, FI offers high sensitivity, ease of operation, low cost, and short acquisition times.However, its tissue penetration depth is limited due to significant light absorption and scattering by tissues.PET, on the other hand, is a highly sensitive molecular imaging technique capable of generating whole-body images with deep tissue penetration.Nevertheless, PET suffers from relatively poor spatial resolution.MRI combines deep tissue penetration and high spatial resolution but exhibits lower sensitivity, making it challenging to detect biomolecules at low concentrations.PAI, which integrates optical and ultrasound imaging, operates on a "laser in, sound out" mechanism, producing three-dimensional images with high sensitivity and spatial resolution.However, enhancing the quantum yield of nanoprobes in the NIR-II range remains a pressing issue. [148,149][151] Multimodal imaging can ensure early and accurate determination of tumor location.Combining AIEgens with contrast agents in magnetic resonance imaging (MRI) to form AIE-Gd probes is an ideal approach for constructing dual-modal imaging and therapeutic agents. [152]ang et al. [152] first synthesized a hydrophobic molecule (TQ-TPA) and an amphiphilic molecule (2TPE-Gd), both of which possess AIE characteristics.Subsequently, they chose DSPE-PEG to load these two molecules to form nanomaterials (TGdTT NMs).Compared with the clinical MRI CA Gd-DOTA, the relaxivity (r 1 ) of TGdTT NMs increased fivefold.
TGdTT NMs have good biocompatibility and biocompatibility, enabling in vitro and in vivo MR/NIR-II FL dualmodal imaging, and can effectively generate ROS for cancer cell ablation and tumor suppression (Figure 9A).

Two/three-photon imaging
Although the fluorescence emission of AIE molecules can be adjusted to the entire visible and infrared regions, AIE molecules have a rotatable structure, which limits the size of the conjugated system.Therefore, most AIE molecules have the drawback of shorter absorption wavelengths.Twophoton (or multi-photon) imaging can effectively address the issue of the relatively short absorption wavelengths of AIE molecules.Two-photon NIR light is a powerful tool for deep tissue imaging. [153,154]With the assistance of fluorophores, two-photon fluorescence lifetime microscopy (TPFM) can simultaneously utilize NIR two-photon excitation and NIR one-photon fluorescence for imaging. [155]Moreover, the nonlinear excitation mode of two-photon fluorescence significantly reduces photobleaching effect of fluorescent probes and enhances spatial resolution. [156]AIE dyes are known for their unique optical properties, which can aggregate into nanoparticles to provide a large two-photon absorption cross-section.Qian et al. [157] reported a novel deep red AIE dye TQ-BPN, which emits NIR one-photon fluorescence signal under NIR two-photon excitation.TQ-BPN dye exhibits a two-photon absorption cross-section of 1.61 × 10 4 GM at 1040 nm.Under 1040 nm femtosecond excitation, AIE nanoparticles display a two-photon fluorescence peak at 790 nm with a lifetime of 2.2 ns.Researchers used AIE nanoparticles as contrast agents to obtain two-photon fluorescence lifetime information of the cerebral vascular system in live mice.Even at a depth of 750 µm, numerous vessels as small as 3.17 µm could be observed with a good signal-to-noise ratio.Among various imaging techniques, three-photon (3P) microscopy stands out in the field of in vivo vascular imaging due to its deep penetration capability and sub-micrometer resolution. [158,159]AIEgens are considered effective 3P probes. [160]Xu's team [161] designed and synthesized a series of AIEgens, introducing benzene rings on the donor (D) and acceptor (A) to control molecular deformation, conjugation strength, and D-A relationships.After encapsulation with DSPE-PEG2000, the optimized AIEgens could be successfully applied to 3P microscopy.They can be excited in the near-infrared III region (NIR-III, 1600-1870 nm) and emit in the NIR-I region (700-950 nm).In mice with opened skulls, the 3P microscopy technique based on AIEgens clearly visualized the vascular system within a range of 1700 µm, including microvessels with a diameter of 2.2 µm, F I G U R E 9 (A) Schematic representation of the fabrication process of TGdTT NMs and their application in MR/NIR II FL dual-modal imaging-guided photodynamic therapy.Reproduced with permission: Copyright 2023, Royal Society of Chemistry. [152](B) DPNA-NZ NPs with three-photon excitation and its application in brain vascular imaging.Reproduced with permission: Copyright 2022, American Chemical Society. [161](C) Schematic illustration of the aggregation-driven long-lived NIR-II phosphorescence.Reproduced with permission: Copyright 2021, Wiley-VCH. [162](D) The preparation of AGL AIE dot.The NIR afterglow luminescence mechanism of AGL AIE dots.effectively characterizing the hemodynamics of the vessels (Figure 9B).

Phosphorescence imaging
Fluorescence imaging in the NIR-II window is a highly promising and actively researched technique, yet there has been limited research on optical imaging using NIR-II phos-phorescence.Cheng et al. [162] reported a strategy based on aggregation-induced selective signal activation, relying on the transition of probe's radiative mode from weak fluorescence to strong NIR-II phosphorescence.Copper indium selenide (Cu-In-Se) quantum dots exhibit extremely weak fluorescence in an isolated state.But their aggregated state emits significant light at ∼1045 nm, increasing their emission lifetime by more than 2.7 × 10 3 times.The encapsulation of Cu-In-Se with mesoporous silica nanoparticles (Cu-In-Se@MSN) confirmed the aggregation induced emission mode transition, exhibiting unique phosphorescent emission (Figure 9C).The NIR-II phosphorescent signals enable Cu-In-Se@MSN to exhibit excellent lifetime imaging and accurately identify high-order vascular branching.

Afterglow imaging
Afterglow luminescence refers to the phenomenon where the afterglow substrate can continue to emit light even after stopping light excitation.Due to the separation of laser irradiation and photon acquisition processes, the photon release during the afterglow emission process is relatively controllable.In addition to minimizing background noise, afterglow imaging provides stable luminescent signals and minimal invasiveness for in vivo detection. [163][166] Ding et al. [70] firstly reported NIR afterglow luminescent AIE probe with an exceptionally long afterglow time for facilitating image-guided cancer surgery.The authors first synthesized an enol ether precursor (compound 3) of Schaap's 1,2-dioxetane and two NIR emissive AIEgens, named TPE-DCM and TPE-Ph-DCM, respectively.TPE-Ph-DCM produces singlet oxygen ( 1 O 2 ), oxidizing compound 3 to generate dioxetane, which undergoes chemical excitation.Subsequently, energy transfer back to TPE-Ph-DCM occurs through a series of processes within the nanoparticles, enabling AGL AIE dots to emit NIR light for over 10 days under a single light excitation.The fluorescence quantum yield and 1 O 2 yield of TPE-Ph-DCM are higher than those of TPE-DCM.In vivo, the NIR afterglow signal of AGL AIE dots rapidly extinguishes in normal tissues like the liver, resulting in an extremely high signal-to-noise ratio between tumor and liver.By utilizing NIR afterglow imaging, AGL AIE dots can effectively illuminate nearly all tumor nodules, especially submillimeter-sized nodules (Figure 9D).Multicolor afterglow materials have significant application value in data security, optoelectronics, and biological imaging.169] To date, researchers have explored long afterglow emissions in some CDs systems, including phosphorescence and delayed fluorescence, achieving efficient blue, green, and red emissions. [170,171]Qu and his colleagues [172] reported a precise control method for CDs phosphorescent colors from green to NIR based on AIE.The regulation ability of polychromatic phosphorescence primarily arises from energy levels splitting induced by aggregation.Additionally, the uniform surface state of CDs partially avoids ACQ to some extent.The authors developed a solvent-triggered dynamic color-changing property for CDs systems, through which trace amounts of solvent induce the aggregation of CDs, thereby triggering the transition of phosphorescent color from green to red.

Near-infrared chemiluminescence
Chemiluminescence is a technique that uses chemical reactions to generate light for imaging purposes.Compared to fluorescence imaging, chemiluminescence imaging doesn't require an external light source to excite luminescence.It typically exhibits high sensitivity, lower background signals, and deeper tissue penetration, showcasing significant potential in the field of medical imaging. [173]NIR chemiluminescence (CL) has significant advantages in deep tissue imaging.Tang et al. [174] synthesized a NIR CL luminescent material (TBL) with AIE activity by coupling the luminophore unit with the electron acceptor benzothiadiazole and the electron donor triphenylamine.TBL nanoparticles were prepared using F127 as a surfactant.The CL emission duration of TBL nanoparticles can exceed 60 min, which can be used for quantitative (in vitro) and qualitative (in vivo) detection of singlet oxygen ( 1 O 2 ).It is worth noting that the NIR CL emission of TBL nanoparticles can penetrate tissues with a total thickness exceeding 3 cm, showing significantly better performance than NIR fluorescence emission and blue CL emission.CL imaging based on TBL can successfully distinguish between tumors and normal tissues in vivo (Figure 9E).Liu et al. [175] reported a near-infrared chemiluminescence nanoparticle ALPBS containing luminol, AIE dye (TTDC), PCPDBT, and nitric oxide donor (BNN6), which can achieve deep CL imaging guided photothermal NO gas therapy for bacterial infections.Upon intravenous injection, ALPBS accumulates significantly at the infection site and is activated by the over-secreted reactive oxygen species (ROS), generating near-infrared chemiluminescence.This allows for precise tracking of locally induced inflammation caused by the infection.

NIR-AIE materials for therapy
By employing molecular design, AIEgens can be endowed with various functions, allowing molecules to generate ROS and exhibit photothermal properties for the effective eradication of cancer cells and pathogens.This primarily includes photothermal therapy, photodynamic therapy, and combination therapy.

Photothermal therapy (PTT)
Photothermal therapy is a method that utilizes photothermal agents (PTAs) to convert light energy into heat, which is used to ablate tumor cells. [176]This method offers advantages such as short treatment time and significant therapeutic effect. [177]PTA absorbs the energy of photons under light irradiation and activates them from ground state singlet to excited singlet.Subsequently, the energy excited by electrons undergoes a non-radiative decay vibrational relaxation, returning to the ground state through collisions between PTA and surrounding molecules.The increased kinetic energy heats up the surrounding microenvironment, resulting in thermal effects.Among them, the photothermal conversion efficiency and biocompatibility of photothermal agents have a significant impact on the therapeutic effect. [178]PTA mainly includes metal nanoparticles, transition metal disulfides (TMDCs), carbon materials and their analogues, Mxenes, and conjugated molecular materials, which have been widely explored for PTT applications.In comparison to traditional PTAs, AIEgens exhibit superior photostability and high photothermal conversion efficiency through structural optimization. [179]AIEgens significantly suppress non-radiative transition processes in their aggregated state, allowing them to exhibit efficient luminescence and generate reactive oxygen species with cytotoxic properties.[182] For example, the covalent organic framework based on AIEgen [183] , BBT-C6T-DPA(OMe) [184] , TPTQ, constructed using 6,7diphenyl-[1,2,5] thiadiazoline [3,4-g] quinoline as a receptor and thiophene as a π bridge [65] , has a wide range of applications in suppressing malignant arrhythmias, combating infections and bacterial resistance at wound sites, and eradicating tumors (refer to specific information in Table 4).Lu's team [185] used small molecule fluorescent probe BPBBT and imaged in the NIR-II range to construct a nano theranostic system (BPBBT NPs) with the assistance of human serum albumin (HSA), which combines NIR-II fluorescence imaging and photothermal therapy functions.The small molecule fluorescent probe BPBBT has a planar structure of its fluorescent groups in non-polar organic solvents, resulting in strong fluorescence and low photothermal conversion efficiency.
In polar solvents, intramolecular rotation of the molecule leads to an increase in the dihedral angle of the fluorescent molecule, disrupting the original planar structure and enhancing photothermal conversion performance.The dual nature of BPBBT hindered its ability to simultaneously function in fluorescence imaging and photothermal therapy.HSA exhibits a high affinity for the small-molecule fluorescent probe BPBBT.When HSA binds to BPBBT, it restricts the intramolecular rotation of BPBBT, thereby regulating its optical properties.This enables the small-molecule fluorescent probe BPBBT to possess both fluorescence imaging and photothermal conversion capabilities.Nanotherapeutic agents (BPBBT NPs) prepared with albumin as a carrier can also promote the specific delivery and efficient accumulation of the small-molecule fluorescent probe BPBBT in tumor regions.

Photodynamic therapy (PDT)
Photodynamic therapy (PDT) is a typical phototherapy technique that has gained widespread attention. [186,187]PDT relies on non-toxic photosensitizers, light, and endogenous molecular oxygen to treat cancer.[190] PDT, characterized by high selectivity and low side effects, emerges as a non-invasive cancer treatment option that significantly spares patients from the adverse effects associated with traditional methods such as radiation therapy, chemotherapy, and surgery.[193] Multidrug resistant (MDR) bacterial infections are an urgent global public health issue. [194]Developing alternative treatment methods and drugs for MDR bacterial infections still faces many challenges.PDT has been considered an effective strategy for treating bacterial infections.The antimicrobial properties of PDT largely depend on photosensitizers that can generate reactive oxygen species (ROS) under light irradi-ation, thereby inactivating bacteria. [195]ROS can generally be divided into two types: 1) Type I, including hydroxyl radicals (•OH), superoxide anions (O 2 − •), and hydrogen peroxide (H 2 O 2 ) generated during electron transfer processes; and 2) Type II, which involves singlet oxygen ( 1 O 2 ) generated during energy exchange processes.Tang's group [196] has reported a series of highly efficient NIR-AIE Type I photosensitizers for imaging-guided photodynamic inactivation of MDR bacteria (Figure 10A).Inspired by the introduction of cyanide groups in drug molecule design to enhance affinity for target proteins, [197] the group introduced cyanide groups into the TTPy molecular structure.Additionally, they ingeniously introduced heavy atoms such as Br and I through molecular engineering to construct a series of AIE photosensitizers with NIR emission.The introduction of cyanide groups in the molecular structure enhances interactions with the outer membrane phospholipids of both Gram-negative (G−) and Gram-positive (G+) bacteria by limiting molecular motion for broad-spectrum imaging.Furthermore, the cyanide group serves as a receptor to increase donor-acceptor strength, greatly promoting intramolecular charge transfer and spatial separation between the highest occupied molecular orbital and lowest unoccupied molecular orbital, resulting in a reduced energy gap (ΔEst) between singlet (S1) and triplet (T1) states.Additionally, the heavy atom effect facilitates inter-system crossing, inducing the generation of excited triplet states and favoring the production of type I ROS.TTCPy series photosensitizers can efficiently generate type I •OH and O 2 − , and achieve broad-spectrum bacterial imaging guided photodynamic therapy.Under white light irradiation, these photosensitizers exhibit highly efficient bactericidal activity against methicillin-resistant Staphylococcus aureus (MRSA) and MDR Escherichia coli (MDR E. coli).

Synergistic therapy
Phototherapy is a potential field in precision medicine that has gained increasing attention in terms of antibacterial and antitumor applications. [198]Photothermal therapy (PTT) and photodynamic therapy (PDT) effectively convert absorbed light energy into local heat or produce toxic ROS to kill tumor cells.Combining these two methods can achieve maximum therapeutic effect and survival rates. [199]Phototherapy is employed to solve bacterial infections by killing some antibiotic-resistant bacteria without using antibiotics or in combination with antibiotics.Tang et al. [200] [196] (B) Schematic illustration of DTTVBI NPs for NIR-II FLI-guided PTT and type-I PDT phototherapy of tumor.Reproduced with permission: Copyright 2023, American Chemical Society. [204](C) Schematic illustration of the self-assembly of the metallacage C-DTTP and the dual modal imaging-guided PTT/PDT by using the metallacage-loaded nanoparticles.Reproduced with permission: Copyright 2022, American Chemical Society. [205](D) Schematic illustration of the design and application of TPA-TBT nanoparticles in fluorescence imaging-guided theranostics for cancers.Reproduced with permission: Copyright 2023, American Chemical Society. [206](E) Schematic illustration of chemical structures of NIR-AIEgens and applications of TACQ for FLI and PTI imaging guided synergistic CT, PTT, and PDT.Reproduced with permission: Copyright 2021, American Chemical Society. [208](F) (f1) ALPBs are synthesized by double emulsion method using PLGA-PEG5000 as a matrix to encapsulate TTDC, luminol, BNN6 and PCPDTBT.(f2) ALPBs applied to CL imaging and synergistic photothermal-NO therapy of bacterial infection.Reproduced with permission: Copyright 2022, Elsevier. [175](G) Dual-functional AIE materials used for Gram-positive bacterial detection and efficient photodynamic killing.Reproduced with permission: Copyright 2019, American Chemical Society. [209]

Cancer
Optical diagnostics and therapy have received widespread attention due to their significant potential in revolutioniz-ing traditional cancer treatment strategies. [201]Integrating "imaging" and "therapeutic" functions into a single molecule while accurately targeting tumor sites has proven to be an outstanding approach for diagnosing and treating cancer. [202,203]luorescence guided phototherapy, including photodynamic and photothermal therapy, is considered an emerging noninvasive strategy for cancer treatment.Traditional optical diagnostic and therapeutic methods often encapsulate multiple components with independent functions to produce multifunctional nano reagents.However, most multi factor optical diagnostic and therapeutic systems suffer from issues like complex structure, poor reproducibility, insufficient optical therapeutic performance, and damage to normal tissues, which has severely hindered their clinical conversion.Tang et al. [204] designed a NIR-II photosensitizer (DTTVBI) with AIE properties and a reversible pH switch using molecular engineering technology for precise tumor targeted fluorescence imaging (FLI) guided phototherapy.DTTVBI has strong intramolecular charge transfer, efficient intermolecular crosslinking enhancement, and sufficient intramolecular motion characteristics.Under 808 nm laser irradiation, it can promote the generation of type I superoxide anions and exhibit excellent photothermal performance.Biocompatible DTTVBI nanoparticles show significantly anti-tumor effect in vitro and in xenograft models derived from colon cancer patient (Figure 10B).Constructing supramolecular coordination complexes with cancer diagnostic and therapeutic functions is an important but highly challenging research task.Tang et al. [205] used a groundbreaking method to assemble a prismatic metal cage C-DTTP with efficient fluorescence emission in NIR-II region by combining a fourarmed ligand with a 90  10C).Organic molecules hold great promise as therapeutic and diagnostic agents due to their simple structure, ease of modification, and excellent biocompatibility.Tang's team [206] has developed a multifunctional therapeutic and diagnostic platform based on the AIE molecule TPA-TBT.This platform features NIR emission, high fluorescence quantum yield, stable ROS generation, and high photothermal conversion efficiency.In vivo, TPA-TBT nanoaggregates exhibited excellent photodynamic and photothermal therapeutic effects (Figure 10D).Despite the enhanced permeability and retention (EPR) effect has been widely used in the field of nanomedicine for decades, it still cannot solve the low delivery efficiency of nanoparticle, with only about 0.7% of the dosage reaching solid tumors.Moreover, delivery based on EPR or other particle surface modifications often requires 24 h or longer to effectively accumulate in tumor regions.To address these two major issues, Tang's team [207] designed an integrated NIR multifunctional nanoaggregate phototherapy platform based on the photoinduced thermoacoustic process (PTA).Starting from classical AIE molecules, they developed three candidate photosensitizers (TBT-2(1P-DPA), TBT-2(2P-DPA), and TBT-2(TP-DPA)) by tuning the π-bridge in small molecules with a D-(π)-A-(π)-D skeleton.TBT-2(TP-DPA), with a thiophene bridge, demonstrated the most balanced potential for NIR imaging and therapy.After simple encapsulation with DSPE-PEG, the nanoaggregate exhibited a high photothermal conversion efficiency of up to 51% while maintaining a high quantum yield in the NIR region.This platform enabled multimodal imaging, including fluorescence imaging (FLI), photothermal imaging (PTI), and photoacoustic imaging (PAI).Subsequently, the material was excited with pulsed light to achieve effective delivery to the tumor area within 40 min.In subsequent photothermal therapy, the solid tumors of 4T1 tumor bearing mice were effectively eliminated, surpassing traditional EPR in terms of efficacy and therapeutic effect.Mitochondria, as essential organelles in cells, provide energy for normal cellular activities.Targeting mitochondria with PTT and PDT can directly inhibit energy production in cancer cells, leading to their death.Mitochondrial autophagy, as a protective mechanism against cellular stress, has a dual role in inhibiting or promoting cancer cell death.Therefore, developing multifunctional therapeutic agents with mitochondrial autophagy-regulating capabilities and excellent PTT and PDT effects is of significant research significance for efficient and precise cancer diagnosis and treatment.Tang et al. [208] reported a NIR-AIE molecule (TACQ) with mitochondrial autophagy-regulating capabilities, achieving targeted multimodal diagnosis and therapy of cancer.Due to strong push-pull electronic effects and distorted molecular configuration, TACQ exhibited strong NIR fluorescence, high photothermal conversion efficiency (55%), and excellent ROS generation capabilities in its aggregated state.TACQ possesses suitable lipophilicity and cationic properties, enabling selective enrichment within cancer cell mitochondria.Importantly, TACQ can induce mitochondrial autophagy and block the autophagic pathway, leading to cancer cell apoptosis.The multifunctional therapeutic agent TACQ combines mitochondrial autophagy intervention with photo diagnosis and therapy, enabling a combination of chemotherapy, PTT, and PDT guided by fluorescence/photothermal imaging (Figure 10E).

Bacteria
Bacterial infections are the main cause of many inflammatory diseases, such as sepsis, pneumonia, and inflammatory bowel disease.However, clinical diagnostic procedures, including tissue biopsy, bacterial culture testing, and biochemical analysis, are invasive, time-consuming, and inefficient.This may lead to serious delays in treatment, especially for deep tissue infections.On the other hand, the excessive use of antibiotics has led to the evolution of bacterial resistance and the emergence of super bacteria, posing significant challenges to the treatment of drug-resistant infections.Compared with traditional antibiotics, the antibacterial activity achieved by Fenton reaction can effectively prevent the development of bacterial resistance.Photogenerated electrons can significantly accelerate the Fenton reaction and increase the production of ROS.Sun et al. [210] revealed the Fenton-like activity of nickel-coordinated phthalocyanines and solar Fenton activity, which avoids the use of UV light to trigger the reaction, providing a new perspective for photo-induced antimicrobial agents.Antibacterial hydrogels containing antimicrobial agents have been widely used in postoperative infection prevention, wound healing, and tissue engineering research.However, the abuse of antibiotics has led to enhanced bacterial resistance, gradually rendering traditional antibiotic ineffective.Recently, Jiang's team [211] studied the hydrogel based on AIEgens for wound healing and non-invasive visible research.They covalently introduced a novel water-soluble AIEgen into hydroxypropyl chitosan to construct a co-antibacterial, heat-sensitive hydrogel (red fluorescent hydroxypropyl chitosan, redFHPCH) that can be triggered by fluorescence and sunlight.The thermosensitive redFHPCH solution can be injected and flowed at low temperatures, and can be converted into gel at body temperature.RedFHPCH hydrogel exhibits excellent AIE fluorescence imaging properties in the red/NIR region and can efficiently generate ROS under sunlight.Furthermore, the redFHPCH hydrogel with positively charged quaternary ammonium groups has a strong synergistic antibacterial effect on infected wounds under sunlight.Chemical luminescence technology (CL) does not depend on external light excitation and has the characteristics of high sensitivity, low fluorescence background, and deep tissue penetration. [212,213]Liu et al. [175] integrated luminol, AIE dye (TTDC, PCPDTCT), and a thermal-responsive NO donor (BNN6) into a therapeutic nanoplatform for deep CL imaging and synergistic photothermal-NO therapy of bacterial infections.PCPDTCT is a commercial photothermal agent (PTA) with NIR emission and excellent photothermal conversion efficiency.NIR light can stimulate PCPDTCT to generate heat effectively, triggering the release of NO from BNN6 through a heat-induced activation process.To achieve effective NIR CL imaging, a novel fluorescent molecule, TTDC, with AIE characteristics was synthesized through a one-pot cascade reaction.By emulsification, these four components were co-encapsulated in PLGA-PEG5000 to form uniform ALPBs nanoparticles.After intravenous injection, ALPBs gradually accumulate at the site of bacterial infection due to inflammation-induced vascular leakage.Under the condition of excessive ROS in acute inflammation, luminol within ALPBs can be activated to produce luminescence, further exciting nearby PCPDTCT to generate NIR CL.Subsequently, under the guidance of CL imaging, photothermal-NO therapy is performed under 808 nm laser irradiation to quickly eliminate bacteria and reduce inflammation.The application of ALPBs makes it possible for the detection and precise treatment of localized deep bacterial infections (Figure 10F).Tang et al. [209] reported a series of dual-functional AIE materials that can be used for Gram-positive bacterial detection and efficient photodynamic killing.They systematically investigated the structure-activity relationship between molecular structure and bacterial imaging, photodynamic antibacterial effects.Efficient NIR-AIE probe have been used to control Staphylococcus aureus infection in rat skin wounds.In this work, they developed a series of AIE molecules with gradually redshifted absorption and emission wavelengths based on the innovative concept of AIE.TPy, MeOTTPy, and TPE-TTPy all exhibit near-infrared fluorescence emission (Figure 10G).

Others
Protein folding abnormalities are associated with many diseases, including various neurodegenerative diseases.βamyloid protein (Aβ) is one of the primary pathological biomarkers of Alzheimer's disease (AD), which forms toxic aggregates through incorrect assembly of Aβ monomers.Cur-rently, therapeutic strategies for AD targeting Aβ protein mainly focus on interfering with the abnormal assembly of Aβ or breaking down pre-formed fibrils.A novel approach for treating AD involves the development of specific photosensitizing molecules that generate singlet oxygen to cause photodamage to Aβ, thereby reducing its neurotoxicity.Yan et al. [214] has developed a series of NIR photosensitizers that can be used for specific imaging and photodamaging Aβ aggregates.The team designed a series of D-π-A photosensitizers (QM20-QM22) with quinoline-imidazolium as the electron acceptor and introduced a dimethylaniline group as the electron donor to enhance the Aβ aggregation-targeting properties of the photosensitizers.Before the photosensitizer molecules bind to the target, the primary energy dissipation process is the rapid non-radiative decay of the twisted intramolecular charge transfer (TICT) process, resulting in weak emission and low singlet oxygen ( 1 O 2 ) production.
After the photosensitizer binds specifically to Aβ aggregates, the reduced non-radiative transition caused by the TICT process leads to increased fluorescence emission and singlet oxygen production, enabling specific imaging and photodamage of Aβ aggregates.

CONCLUSION AND PERSPECTIVES
Aggregation-induced emission (AIE) is a photophysical phenomenon, and AIE materials have significant advantages, including high brightness, good biocompatibility, strong photostability, and positive relationship between luminescence and concentration.These characteristics make AIE materials highly promising for a wide range of applications in the biomedical fields such as detection, bioimaging, photodynamic therapy, and photothermal therapy.Meanwhile, NIR properties exhibit unique advantages in sensing, imaging, and therapeutic applications.To comprehensively analyze the progress in this field, we conducted a bibliometric analysis using "AIE" and "NIR" as keywords.According to chronological order, the development of NIR-AIE can be divided into two stages.The first stage, spanning from 2008 to 2015, can be characterized as the "discovery and initial stage".It was in 2001 that Tang et al. initially uncovered the concept of AIE, presenting a complete departure from the well-known ACQ phenomenon.This groundbreaking revelation opened new avenues for the development of solid organic luminescent materials.Notably, it wasn't until 2008 that research teams led by Wang [215] and Ye [216] combined the concepts of NIR and AIE, laying the foundation for potential applications in the biomedical domain.However, during this early stage, the research on NIR-AIE remained relatively limited, with few related studies.
The second stage, starting in 2017 and extending to the present day, represents the "rapid development stage".During this phase, researchers embarked on a more profound exploration of the structure-function relationship inherent in NIR-AIE materials.Through the comprehensive analysis of publishing countries/institutions, authors, journals, keywords, influential papers, and research hotspots in the field of NIR-AIE, it is evident that Chinese and domestic institutions have emerged as prominent contributors, closely followed by Singapore and the United States.International collaboration has also notably intensified, fostering a dynamic and interconnected research landscape.Notably, the research team led by Ben Zhong Tang has solidified its leading position, with the Hong Kong University of Science and Technology emerging as the most active institution in this area of study.In terms of publication platforms, "Dyes and Fragments" have published the highest number of articles, while "Advanced Materials" has garnered the most citations.
According to the dual-map overlay results of journals, most publications are published in journals related to chemistry, materials, physics, molecules, biology, and genes.Most publications are cited in journals related to physics, materials, chemistry, molecules, biology, and immunity.Ju Mei from the Hong Kong University of Science and Technology stands out as the most cited author, with her influential review titled "Aggregation Induced Emission: Together We Shine, United We Soar!", amassing an impressive 214 citations.Subsequently, keyword co-occurrence networks, clustering analysis, and keyword burst analysis were vividly visualized using different software.The AIE research field has formed a multidisciplinary system with comprehensive science as the core discipline.Recent research endeavors have primarily concentrated on two significant fronts.On the one hand, there is a notable emphasis on the development of NIR-AIE probes and the fine-tuning of their luminescence performance, including near-infrared photoluminescence, AIE-active luminophore, photosensitizer, ultradeep intravital two-photo microscopy, diazine-based luminescent material.On the other hand, the focus has extended to the biomedical arena, encompassing research on photodynamic therapy, cancer, cell, vivo pharmacology, and related applications.We provide a unique perspective for the development of the AIE field through a comprehensive bibliometric analysis.Additionally, we discussed the latest developments in NIR-AIE and its associated branches.The development of NIR-AIE has significantly influenced both the materials and biology domains, infusing fresh vitality into these fields.However, with the continuous deepening of research on AIE materials, there are still some new challenges.Firstly, although a large number of AIE materials have been reported, there is still a need for in-depth exploration of their distinctive luminescent properties.The mechanism of luminescence enhancement of AIE molecules is still unclear.Particularly, achieving controlled synthesis of NIR-AIE materials presents a significant challenge, and the research on methods to regulate AIE luminescence in the NIR spectrum lacks systematic development.Deeply understanding the relationship between molecular structure, aggregated state structure, and performance is paramount for unlocking the full potential of these materials.The development of materials such as phosphorescent AIE, dual/multi photon absorption AIE, and afterglow AIE has provided new technological means for disease diagnosis and treatment, but further development is still needed.The development and investigation of multifunctional AIE molecules for multimodal diagnosis and treatment are in their infancy, and their structure-activity relationship remains unclear.Secondly, translating AIE materials into clinical applications poses significant challenges, and a notable gap exists in terms of safety assessment, in vivo metabolism, and related aspects.Further research is essential in these areas to ensure the safe and effective clinical utilization of AIE materials.After 15 years of dedicated development, NIR-AIE materials have made significant progress in both molecu-lar design and mechanism research.NIR-AIE materials has extensive applications in related fields such as biosensing, bioimaging, photothermal therapy, photodynamic therapy, and so on.However, the application of AIE materials still focuses on the detection and treatment of cancer and bacteria.Their utilization in autoimmune diseases remains relatively limited.Although significant progress has been made in the field of NIR-AIE, we eagerly look forward to standing on the shoulders of giants and achieving innovative development in this exciting research field.

C O N F L I C T O F I N T E R E S T S TAT E M E N T
The authors declare no conflicts of interest.

F I G U R E 1
(A) Number of publications in different countries; (B,C) Publication weight and cooperation network of different countries related to NIR-AIE; (D) Visualization of organizations related to NIR-AIE.

F I G U R E 2
Visualization of (A) journals and (B) co-cited journals on research of NIR-AIE; (C) Dual-map overlay of journals.In this study, CiteSpace was utilized to construct dual maps of journals with a 2-year time slice (Figure 2C).The left side represents the citing journals, while the right side represents the cited journals, with each curved line depicting the flow of information from right to left.The sources of information serve as the theoretical and technical foundations for NIR-AIE research, and the information flow represents the development and evolution of research in the macroscopic world.Convergence points indicate where research hotspots and trends are likely to aggregate in fields such as physics, materials, chemistry, molecular biology, and immunology.AIE materials fundamentally address the ACQ challenges faced by traditional organic luminescent materials, making them a hot topic in current luminescent material research with numerous original achievements.The development of NIR-AIE, in particular, has propelled interdisciplinary research beyond the initial domains of chemistry, materials, and physics into the fields of biology, immunology, and medicine.

F I G U R E 3
Visualization of (A) authors and (B) co-cited authors on research of NIR-AIE; Visualization of (C) citation and (D) co-cited references on research of NIR-AIE.

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I G U R E 4 (A) Visualization of keywords; (B) Cluster analysis of keywords.

F I G U R E 5
The top 10 references with the strongest citation bursts.
Note: a (tetrahydrofuran, THF); b (water, H 2 O); c (dimethyl sulfoxide, DMSO); d (acetonitrile, ACN).charge transfer, leading to non-radiative transitions and a narrowed bandgap.Building upon their earlier work, Tang's research team has successfully developed a new class of near-infrared-emitting molecules with a smaller conjugated system yet longer absorption and emission wavelengths.The monomers used in this class of molecules include the commercial 4,7-dibromobenzo[c]−1,2,5-thiadiazole (BT-2Br

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I G U R E 7 (A) A lateral flow immunoassay method employing AIE 810 NP for early detection of IgM and IgG against SARS-CoV-2.Reproduced with permission: Copyright 2021, American Chemical Society.[88](B) Schematic illustration of molecular and imaging of liver injury.(b1) Molecular structure and proposed mechanism of DPXBI in response to viscosity.(b2) Demonstration of utilizing DPXBI to visualize viscosity changes in the context of drug-induced liver injury.(b3) Diagram depicting the in vivo visualization of lesions associated with hepatic ischemia-reperfusion injury.Reproduced with permission: Copyright 2023, Elsevier.

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I G U R E 8 (A) Strategic development of NIR-AIE-active probes for detecting Aβ deposition.(a1) Commercial probe ThT based on the always-on pattern.(a2,a3) (B) A novel AIE-based TCM probe for precise mitochondrial trapping.(b1) Molecular structures of mitochondrial probes MTG and MTR.(b2) Molecular structures of TCM-1, TCM-2 and TCM-3.(b3) Regulating aggregation state and charge density for fluorescence "off-on" and mitochondrial targeting.Reproduced with permission: Copyright 2019, Wiley-VCH. [131](C) Examination of nLDs in HepG2 cells treated with OA.Nuclei were labeled with Hoechst 33342 (blue), and the nLDs were stained with DTZ-TPA-DCN (red).(c1) The image on the edge represents the orthogonal maximum intensity projection of the cells.(c2) The rotated 3D reconstruction of the cell.Scale bar: 5 mm.Reproduced with permission: (E) (e1) In vivo images and (e2) signal-to-noise ratio of CL signals in hair-shaved mice after subcutaneous injection of TBL dots.(e3) In vivo CL images and (e4) signalto-noise ratio of normal tissue (left) and tumor area (right) after injection of TBL dots.(e5) The change of mice body weight in different groups.Reproduced with permission: Copyright 2020, Wiley-VCH.

F I G U R E 1 0
(A) (a1) Molecular configurations of designed type-I AIE-PSs.(a2) Photophysical and photochemical mechanisms of type-I and type-II processes and image-guided broad spectrum antibacterial application of type-I AIE-PSs.Reproduced with permission: Copyright 2022, Wiley-VCH.

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U T H O R C O N T R I B U T I O N S Qian He used bibliometric software to analyze the data.Meiyiming Wang and Li Zhao used VOSviewer software to analyze the data.Qian He and Meiyiming Wang contribute equally to this work.Liyun Zhang, Wenjing Tian, and Bin Xu are responsible for supervision and the final proofreading.All authors have given approval to the final version of the manuscript.A C K N O W L E D G E M E N T S The authors acknowledge the financial support by Talent Introduction Research Initiation Fund of Shanxi Bethune Hospital (2022RC04), Basic Research Program Youth Science Research Project of Shanxi province (202203021212096), Shanxi Province Clinical Theranostics Technology Innovation Center for Immunologic and Rheumatic Diseases (CXZX-202302), and Research Project Plan of Shanxi Provincial Administration of Traditional Chinese Medicine (2023ZYYB2021).This work was financially supported by National Natural Science Foundation of China (21835001), and the Fundamental Research Funds for the Central Universities of China.All authors are grateful for assistance from the following research platforms: Shanxi Province Clinical Research Center for Dermatologic and Immunologic Diseases (Rheumatic diseases), Shanxi Province Clinical Theranostics Technology Innovation Center for Immunologic and Rheumatic Diseases.
Top 10 journals and co-cited journals on research of NIR-AIE.Top 10 authors and co-cited authors on research of NIR-AIE.
TA B L E 1

NIR-AIE materials Structure Absorption wavelength/nm Emission wavelength/nm Bandgap/eV Ref.
The absorption, emission, and bandgap of NIR-AIE materials.

AIE materials Structure Absorption wavelength/nm Emission wavelength/nm Bandgap/eV Ref.
• Pt receptor Pt(PEt 3 ) 2 (OTf) 2 .The maximum emission wavelength of C-DTTP is 1005 nm, and the photothermal conversion efficiency is as high as 39.3%.Compared with the precursor ligand, its singlet oxygen generation performance is significantly improved.