Research Progress of Aggregation-Induced Emission Molecules for Fluorescence Imaging Therapy

doi:10.19894/j.issn.1000-0518.250010

Chinese Journal of Applied Chemistry ›› 2025, Vol. 42 ›› Issue (6): 741-756.DOI: 10.19894/j.issn.1000-0518.250010

• Review •

Research Progress of Aggregation-Induced Emission Molecules for Fluorescence Imaging Therapy

Zhen-Cao WANG, Ning LYU, Liang-Fang CHEN, Yue-Feng RAO()

Department of Clinical Pharmacy，the First Affiliated Hospital，Zhejiang University School of Medicine，Hangzhou 310003，China

Received:2025-01-05 Accepted:2025-05-07 Published:2025-06-01 Online:2025-07-01
Contact: Yue-Feng RAO
About author:raoyf@zju.edu.cn

Abstract

Abstract:

Aggregation-induced emission （AIE） molecules have been widely used in research fields such as bioimaging and biotherapy due to their easy modification， strong resistance to photobleaching， high fluorescence imaging signal-to-noise ratio， and good biocompatibility. Based on these characteristics， AIE molecules have been developed as disease diagnostic agents that can specifically recognize the environmental signals of lesion areas， thereby aggregating in the disease area and generating bright fluorescence signals to locate the lesion site. This approach can visualize the lesion in situ in real time and has attracted much attention. In addition， on the basis of imaging diagnosis， the therapeutic capabilities of AIE molecules have been further developed and can be used as photothermal therapy agents， photodynamic therapy agents， etc.， promoting the rapid development of the field of imaging diagnosis combined with phototherapy. Therefore， this article reviews the research progress of AIE molecule-targeted imaging combined with phototherapy in recent years （2020-2024）， and discusses in detail the relationship between the molecular structure design and fluorescence imaging and phototherapy effects， hoping to bring new ideas to the development of photodiagnosis and therapy.

Key words: Aggregation-induced emission, Photodynamics therapy, Photothermal therapy, Imaging collaborative therapy

CLC Number:

O644

Zhen-Cao WANG, Ning LYU, Liang-Fang CHEN, Yue-Feng RAO. Research Progress of Aggregation-Induced Emission Molecules for Fluorescence Imaging Therapy[J]. Chinese Journal of Applied Chemistry, 2025, 42(6): 741-756.

Figures/Tables 12

Fig.1 Jablonski schematic of AIE molecular imaging and therapy

Fig.2 Schematic diagram of integrated diagnosis and treatment of AIE molecules after laser excitation

Fig.3 （A） M1 responds to viscosity， visualizes fatty liver in vivo， and photodynamically treats cancer［47］；（B） A schematic of the selective targeting of tumor cells in pH-responsive nanoaggregates M2-1 and M2-2 for precise photodynamic therapy［48］；（C） Schematic diagram of working principle of M3［49］

Fig.4 Schematic diagram of M4 targeted tumor therapy［51］

Fig.5 （A） Schematic diagram of cationic molecular engineering strategy for improving PDT performance；（B） The illumination time-course plots of promoting DCFH fluorescence enhancement by m5-1， M5-1， m5-2 and M5-2；（C） The illumination time-course plots of ABDA degradation by m5-1， M5-1， m5-2 and M5-2；（D） Survival rate of Hela cells after different concentrations of M5-2 photodynamic therapy；（E） Survival rate of Hela cells after different concentrations of M5-1 photodynamic therapy［45］

Fig.6 The structure and organelles of the photosensitizer M6-（n） target， M6-3 PDT and promote anti-tumor immunity in mice［46］

Fig.7 （A） Chemical structure of photosensitizer M7；（B） Schematic diagram of M7's dual response to nucleic acid and HDACs；（C） After entering the nucleus， M7 can not only interact with HDACs to inhibit cell proliferation， but also precisely destroy telomeres and nucleic acids through［52］

Fig.8 （A） Molecular structure and different organelle targeting of three AIE photosensitizers M8-（1~3）；（B） Schematic diagram of synergistic therapy with three AIE photosensitizers［53］

Fig.9 （A） The structural formula of M9-1， M9-2 and M9-3 and the infrared thermal imaging image after laser irradiation［57］；（B） M9-4 PTT policy diagram［58］；（C） M9-5 structure formula and PTT strategy diagram［59］

Fig.10 （A） m10-1 schematic diagram of treatment strategies［60］；（B） m10-2 schematic diagram of treatment strategies［61］；（C） Therapeutic strategy diagram of anti-HSP enhancement of PTT based on M10-3［62］

Fig.11 （A） M11-1 schematic diagram of treatment strategies［63］；（B） M11-2 schematic diagram of treatment strategies［64］；（C） M11-3 schematic diagram of treatment strategies［65］

References 65

1	XU Z R， JIANG Y H， FAN M Z， et al. Aggregation-induced emission nanoprobes working in the NIR-Ⅱ region： from material design to fluorescence imaging and phototherapy［J］. Adv Optical Mater， 2021， 9（20）： 2100859.
2	CHEN D D， XIAO T， WANG L J， et al. A simple “spraying” fluorescence-guided surgery by AIE probes for liver tumor resection through configuration-induced cross-identification［J］. Aggregate， 2024， 5（4）： e550.
3	KAMKAEW A， LIM S H， LEE H B， et al. BODIPY dyes in photodynamic therapy［J］. Chem Soc Rev， 2013， 42（1）： 77-88.
4	ZHOU P， HAN K. ESIPT-based AIE luminogens： design strategies， applications， and mechanisms［J］. Aggregate， 2022， 3（5）： e160.
5	GONG Z C， RONG X J， SUI G M， et al. Intriguing optical properties due to the intermolecular interaction between AIE and ACQ materials［J］. Adv Opt Mater， 2023， 11（14）： 2203075.
6	ZHU W T， WANG J A， LEI K X， et al. Leading edge biosensing applications based on AIE technology［J］. Biosens Bioelectron， 2025， 271： 116953.
7	WU J， LIU W， GE J， et al. New sensing mechanisms for design of fluorescent chemosensors emerging in recent years［J］. Chem Soc Rev， 2011， 40（7）： 3483-3495.
8	SHELLAIAH M， SUN K W. Pyrene-based AIE active materials for bioimaging and theranostics applications［J］. Biosensors， 2022， 12（7）： 550.
9	仝大伟，孔明，向育斌. 含甲氧基四苯乙烯咪唑化合物的合成、光物理性质、理论计算及细胞成像［J］. 应用化学， 2023， 40（9）： 1322-1333.
	TONG D W， KONG M， XIANG Y B. Synthesis， photophysical properties， theoretical calculation and cell imaging of methoxytetraphenylimidazole compounds［J］. Chin J Appl Chem， 2023， 40（9）： 1322-1333.
10	LIU S S， FENG G X， TANG B Z， et al. Recent advances of AIE light-up probes for photodynamic therapy［J］. Chem Sci， 2021， 12（19）： 6488-6506.
11	HU Y C， YIN S Y， LIU W， et al. Rationally designed monoamine oxidase a-activatable AIE molecular photosensitizer for the specific imaging and cellular therapy of tumors［J］. Aggregate， 2023， 4（2）： e256.
12	XU R H， CHI W J， ZHAO Y Z， et al. All-in-one theranostic platforms： deep-red AIE nanocrystals to target dual-organelles for efficient photodynamic therapy［J］. ACS Nano， 2022， 16（12）： 20151-20162.
13	XIANG C B， LIU Y， DING Q H， et al. Precise molecular engineering of multi-suborganelle targeted NIR type-Ⅰ AIE photosensitizer and design of cell membrane-anchored anti-tumor pyroptosis vaccine［J］. Adv Funct Mater， 2025， 35（13）： 2417979.
14	HUANG L， QING D Y， ZHAO S J， et al. Acceptor-donor-acceptor structured deep-red AIE photosensitizer： lysosome-specific targeting， in vivo long-term imaging， and effective photodynamic therapy［J］. Chem Eng J， 2022， 430（2）： 132638.
15	ALAM P， HE W， LEUNG N L C， et al. Red AIE-active fluorescent probes with tunable organelle-specific targeting［J］. Adv Funct Mater， 2020， 30（10）： 1909268.
16	WANG K， GAO H Q， ZHANG Y W， et al. Highly bright AIE nanoparticles by regulating the substituent of rhodanine for precise early detection of atherosclerosis and drug screening［J］. Adv Mater， 2022， 34（9）： 2106994.
17	WANG B， HUANG Y， YANG D， et al. A S-substituted nile blue-derived bifunctional near-infrared fluorescent probe for in vivo carboxylesterase imaging-guided photodynamic therapy of hepatocellular carcinoma［J］. J Mater Chem B， 2023， 11（32）： 7623-7628.
18	CAI X L， LIU B. Aggregation-induced emission： recent advances in materials and biomedical applications［J］. Angew Chem Int Ed， 2020， 59（25）： 9868-9886.
19	YAN D Y， LI T T， YANG Y L， et al. A water-soluble AIEgen for noninvasive diagnosis of kidney fibrosis via SWIR fluorescence and photoacoustic imaging［J］. Adv Mater， 2022， 34（50）： 2206643.
20	CAI X L， LIU B. Multimodal imaging-guided photothermal immunotherapy based on a versatile NIR-Ⅱ aggregation-induced emission luminogen［J］. Angew Chem Int Ed， 2022， 61（27）： e202202614.
21	XU W H， ZHANG Z J， KANG M M， et al. Making the best use of excited-state energy： multimodality theranostic systems based on second near-infrared （NIR-Ⅱ） aggregation-induced emission luminogens （AIEgens）［J］. ACS Mater Lett， 2020， 2（8）： 1033-1040.
22	FENG G X， QIN W， HU Q L， et al. Cellular and mitochondrial dual-targeted organic dots with aggregation-induced emission characteristics for image-guided photodynamic therapy［J］. Adv Healthc Mater， 2015， 4（17）： 2667-2676.
23	LI Q F， ZHANG P J， WANG P X， et al. A combination of covalent and noncovalent restricted-intramolecular-rotation strategy for supramolecular AIE-type photosensitizer toward photodynamic therapy［J］. Aggregate， 2025， 6（2）： e676.
24	王超宇，赵璐，王科伟，等. 共价有机框架的构筑策略及其在肿瘤治疗中应用的研究进展［J］. 应用化学， 2023， 40（7）： 976-994.
	WANG C Y， ZHAO L， WANG K W， et al. Research progress in prearation strategy of covalent organic frameworks and its application in tumor therapy［J］. Chin J Appl Chem， 2023， 40（7）： 976-994.
25	YANG M Q， DENG J R， SU H F， et al. Small organic molecule-based nanoparticles with red/near-infrared aggregation-induced emission for bioimaging and PDT/PTT synergistic therapy［J］. Mater Chem Front， 2021， 5（1）： 406-417.
26	LIU J， CHEN W， ZHENG C， et al. Recent molecular design strategies for efficient photodynamic therapy and its synergistic therapy based on AIE photosensitizers［J］. Eur J Med Chem， 2022， 244： 114843.
27	BAPTISTA M S， CADET J， DI MASCIO P， et al. Type Ⅰ and type Ⅱ photosensitized oxidation reactions： guidelines and mechanistic pathways［J］. Photochem Photobiol， 2017， 93（4）： 912-919.
28	DING D， LI K， LIU B， et al. Bioprobes based on AIE fluorogens［J］. Acc Chem Res， 2013， 46（11）： 2441-2453.
29	SHI J Z， LIANG M S， QIU Y T， et al. Two-pronged strategy： a mitochondria targeting AIE photosensitizer for hydrogen sulfide detection and type Ⅰ and type Ⅱ photodynamic therapy［J］. Talanta， 2025， 282： 127074.
30	MIN X H， YI F， HAN X L， et al. Targeted photodynamic therapy using a water-soluble aggregation-Induced emission photosensitizer activated by an acidic tumor microenvironment［J］. Chem Eng J， 2022， 432： 134327.
31	WANG P P， FANG H B， WANG M M， et al. A mitochondria targeting Ir（Ⅲ） complex triggers ferroptosis and autophagy for cancer therapy： a case of aggregation enhanced PDT strategy for metal complexes［J］. Chin Chem Lett， 2025， 36（1）： 110099.
32	秦洪双，陈书晗，韩旭炜，等. 香豆素衍生物介导的光动力抗耐药菌效果［J］. 应用化学， 2024， 41（11）： 1639-1658.
	QIN H S， CHEN S H， HAN X W， et al. Photodynamic resistance to drug-resistant bacteria mediated by coumarin derivatives［J］. Chin J Appl Chem， 2024， 41（11）： 1639-1658.
33	WAN Q， ZHANG R Y， ZHUANG Z Y， et al. Molecular engineering to boost AIE-active free radical photogenerators and enable high-performance photodynamic therapy under hypoxia［J］. Adv Funct Mater， 2020， 30（39）： 2002057.
34	HAN H H， TIAN H， ZANG Y， et al. Small-molecule fluorescence-based probes for interrogating major organ diseases［J］. Chem Soc Rev， 2021， 50（17）： 9391-9429.
35	杨懿芊，严晓霞，彭皓，等. 近红外二区光驱动的光动力治疗在克服肿瘤乏氧环境中的研究进展［J］. 应用化学， 2024， 41（7）： 925-936.
	YANG Y Q， YAN X X， PENG H， et al. Research progress of near-infrared two-region light-driven photodynamic therapy in overcoming tumor hypoxic environment［J］. Chin J Appl Chem， 2024， 41（7）： 925-936.
36	LIANG M K， LIU L Y， SUN Y， et al. Furan-modified thiadiazolo quinoxaline as an electron acceptor for constructing second near-infrared aggregation-induced emission fluorophores for beyond 1300 nm fluorescence/photoacoustic imaging and photothermal therapy［J］. Aggregate， 2024， 5（2）： e458.
37	YU Y W， NI Z H， XU Y B， et al. Multi-functional AIE phototheranostic agent enhancing αPD-L1 response for oral squamous cell carcinoma immunotherapy［J］. Small， 2024， 20（48）： 2405470.
38	YANG X Q， WANG X Y， ZHANG X， et al. Donor-acceptor modulating of ionic AIE photosensitizers for enhanced ROS generation and NIR-Ⅱ emission［J］. Adv Mater， 2024， 36（28）： 2402182.
39	YANG Z M， ZHANG Z J， SUN Y Q， et al. Incorporating spin-orbit coupling promoted functional group into an enhanced electron D-A system： a useful designing concept for fabricating efficient photosensitizer and imaging-guided photodynamic therapy［J］. Biomaterials， 2021， 275： 120934.
40	HU Y C， GAO X， MA J L， et al. New AIE emitters from the unexpected boron tribromide/boron trichloride-mediated cyclization reaction and application for fluorescence imaging of lipid droplets［J/OL］. Aggregate， 2025， 6： e735.
41	LIU S S， WANG B N， YU Y W， et al. Cationization-enhanced type Ⅰ and type Ⅱ ROS generation for photodynamic treatment of drug-resistant bacteria［J］. ACS Nano， 2022， 16（6）： 9130-9141.
42	CHEN D P， WANG Z C， DAI H M， et al. Boosting O 2 • ^- photogeneration via promoting intersystem-crossing and electron-donating efficiency of Aza-BODIPY-based nanoplatforms for hypoxic-tumor photodynamic therapy［J］. Small Methods， 2020， 4（7）： 202000013.
43	YU J F， WEN Y， LI M， et al. Sterically twisted mitochondria-targeting photosensitizers for augmented near-infrared Ⅱ fluorescence-guided photodynamic immunotherapy［J］. Adv Funct Mater， 2024， 34（38）： 2402663.
44	ZHANG J， MA W， LUO H F， et al. Toward type Ⅰ/Ⅱ ROS generation photoimmunotherapy by molecular engineering of semiconducting perylene diimide［J］. Adv Healthcare Mater， 2024， 13（8）： 2303175.
45	YU Y W， WU S， ZHANG L， et al. Cationization to boost both type Ⅰ and type Ⅱ ROS generation for photodynamic therapy［J］. Biomaterials， 2022， 280： 121255.
46	ZHANG T， YANG X， OU X W， et al. Tailoring the amphiphilic structure of zwitterionic AIE photosensitizers to boost antitumor immunity［J］. Adv Mater， 2023， 35（38）： 2303186.
47	FAN L， ZAN Q， WANG X D， et al. A mitochondria-targeted and viscosity-sensitive near-infrared fluorescent probe for visualization of fatty liver， inflammation and photodynamic cancer therapy［J］. Chem Eng J， 2022， 449： 137762.
48	YANG X Q， XU C H， ZHANG X， et al. Development of sulfonamide-functionalized charge-reversal AIE photosensitizers for precise photodynamic therapy in the acidic tumor microenvironment［J］. Adv Funct Mater， 2023， 33（30）： 2300746.
49	LAM K W K， CHAU J H C， YU E Y， et al. An alkaline phosphatase-responsive aggregation-induced emission photosensitizer for selective imaging and photodynamic therapy of cancer cells［J］. ACS Nano， 2023， 17（8）： 7145-7156.
50	SHI L L， HU F， DUAN Y K， et al. Hybrid nanospheres to overcome hypoxia and intrinsic oxidative resistance for enhanced photodynamic therapy［J］. ACS Nano， 2020， 14（2）： 2183-2190.
51	KANG M M， ZHANG Z J， XU W H， et al. Good steel used in the blade： well-tailored type-Ⅰ photosensitizers with aggregation-induced emission characteristics for precise nuclear targeting photodynamic therapy［J］. Adv Sci， 2021， 8（14）： 2100524.
52	WANG K N， LIU L Y， MAO D， et al. A nuclear-targeted AIE photosensitizer for enzyme inhibition and photosensitization in cancer cell ablation［J］. Angew Chem Int Ed， 2022， 61（15）： e202114600.
53	XU W H， LEE M M S， NIE J J， et al. Three-pronged attack by homologous far-red/NIR AIEgens to achieve 1+1+1＞3 synergistic enhanced photodynamic therapy［J］. Angew Chem Int Ed， 2020， 59（24）： 9610-9616.
54	ZHANG Z J， KANG M M， TIAN H， et al. The fast-growing field of photo-driven theranostics based on aggregation-induced emission［J］. Chem Soc Rev， 2022， 51（6）： 1983-2030.
55	LONG Z， HU J J， YUAN L Z， et al. A cell membrane-anchored nanoassembly with self-reporting property for enhanced second near-infrared photothermal therapy［J］. Nano Today， 2021， 41： 101312.
56	JIN G， HE R， LIU Q， et al. Theranostics of triple-negative breast cancer based on conjugated polymer nanoparticles［J］. ACS Appl Mater Interfaces， 2018， 10（13）： 10634-10646.
57	YAN D Y， HUANG Y， ZHANG J Y， et al. Adding flying wings： butterfly-shaped NIR-Ⅱ AIEgens with multiple molecular rotors for photothermal combating of bacterial biofilms［J］. J Am Chem Soc， 2023， 145（47）： 25705-25715.
58	WANG W T， WU F， MOHAMMADNIAEI M， et al. Genetically edited T-cell membrane coated AIEgen nanoparticles effectively prevents glioblastoma recurrence［J］. Biomaterials， 2023， 293： 121981.
59	WANG J F， LIU Y S， MORSCH M， et al. Brain-targeted aggregation-induced-emission nanoparticles with near-infrared imaging at 1550 nm boosts orthotopic glioblastoma theranostics［J］. Adv Mater， 2022， 34（5）： 2106082.
60	YANG X， YANG T， LIU Q Q， et al. Biomimetic aggregation-induced emission nanodots with hitchhiking function for T cell-mediated cancer targeting and NIR-Ⅱ fluorescence-guided mild-temperature photothermal therapy［J］. Adv Funct Mater， 2022， 32（45）： 2206346.
61	MA G C， LIU Z K， ZHU C G， et al. H₂O₂-responsive NIR-Ⅱ AIE nanobomb for carbon monoxide boosting low-temperature photothermal therapy［J］. Angew Chem Int Ed， 2022， 61（36）： e202207213.
62	HU H T， LI D， DAI W B， et al. A NIR-Ⅱ AIEgen-based supramolecular nanodot for peroxynitrite-potentiated mild-temperature photothermal therapy of hepatocellular carcinoma［J］. Adv Funct Mater， 2023， 33（19）： 2213134.
63	LI D， CHEN X H， WANG D L， et al. Synchronously boosting type-Ⅰ photodynamic and photothermal efficacies via molecular manipulation for pancreatic cancer theranostics in the NIR-Ⅱ window［J］. Biomaterials， 2022， 283： 121476.
64	CUI M H， TANG D S， WANG B， et al. Bioorthogonal guided activation of cGAS-STING by AIE photosensitizer nanoparticles for targeted tumor therapy and imaging［J］. Adv Mater， 2023， 35（52）： 2305668.
65	ZHANG Z J， XU W H， KANG M M， et al. An all-round athlete on the track of phototheranostics： subtly regulating the balance between radiative and nonradiative decays for multimodal imaging-guided synergistic therapy［J］. Adv Mater， 2020， 32（36）： 2003210.

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Research Progress of Aggregation-Induced Emission Molecules for Fluorescence Imaging Therapy

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