Research Progress of Fluorescent Probes Based on Aggregation-Induced Emission for Detection of Biomarkers

doi:10.19894/j.issn.1000-0518.250087

Chinese Journal of Applied Chemistry ›› 2025, Vol. 42 ›› Issue (8): 1035-1056.DOI: 10.19894/j.issn.1000-0518.250087

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Research Progress of Fluorescent Probes Based on Aggregation-Induced Emission for Detection of Biomarkers

Xin-Xin HUANG¹, You-Sheng SHI², Tao DENG³, Chun CAI¹()

^1.School of Chemistry and Chemical Engineering，Nanjing University of Science and Technology，Nanjing 210094，China
^2.Liaocheng Science and Technology Information Research Center，Liaocheng 252000，China
^3.School of Medicine，Foshan University，Foshan 528000，China

Received:2025-03-01 Accepted:2025-06-11 Published:2025-08-01 Online:2025-08-11
Contact: Chun CAI
About author:c.cai@njust.edu.cn

Abstract

Abstract:

Aggregation-induced emission （AIE） has received increasing attention and has been applied widely in various fields such as biochemical analysis and optoelectronic materials. Unlike conventional fluorescent probes， AIE fluorescent probes exhibit strong luminescence due to limited intramolecular movement caused by steric hindrance after aggregation. AIE fluorescent probes reveal higher selectivity， sensitivity， signal-to-noise ratio， and shorter response time. These advantages make AIE a promising tool in biochemical detection， early diagnosis and treatment of disease and cell imaging. Herein， the applications of AIE fluorescent probes in the detection of different biomarkers are summarized. In addition， challenges and development prospects of AIE fluorescent probes in the future are discussed.

Key words: Aggregation-induced emission, Fluorescent probes, Biomarkers, Biological imaging

CLC Number:

O656

Xin-Xin HUANG, You-Sheng SHI, Tao DENG, Chun CAI. Research Progress of Fluorescent Probes Based on Aggregation-Induced Emission for Detection of Biomarkers[J]. Chinese Journal of Applied Chemistry, 2025, 42(8): 1035-1056.

Figures/Tables 25

Table 1 Examples of universally acknowledged biomarkers and related diseases

Diseases	Biomarkers
Lung cancer	Carcinoembryonic antigen （CEA）， neuron specific enolase （NSE）， squamous cell carcinoma antigen （SCCA）， cytokeratin 19 fragment antigen （CYFRA21-1）， biothiols etc.
Liver cancer	Alpha fetoprotein （AFP）， alpha-L fucosidase （AFU）， hepatocyte growth factor （HGF） etc.
Gastric cancer	Carcinoembryonic antigen （CEA）， carbohydrate antigen （CA 19-9， CA72-4）， pepsinogen Ⅰ/Ⅱ（PG Ⅰ/Ⅱ） etc.
Breast cancer	Carcinoembryonic antigen （CEA）， carbohydrate antigen （CA）， tissue polypeptide specific antigen （TPS）， epithelial cadherin （E-cadherin）， alkaline phosphatase （ALP）， nitroreductase （NTR）， H₂S etc.
Cervical cancer	Carbohydrate antigen （CA125，CA72-4）， squamous cell carcinoma antigen （SCCA）， hepatocyte growth factor （HGF）， mixed lineage kinase domain-like protein （MLKL）， Cu²⁺， Hg²⁺etc.
Ovary cancer	Tumor necrosis factor-α （TNF-α）， humanepididymisprotein4 （HE4）， hexokinase2 （HK2）， sequestosome-1 （SQSTM1/p62），β-galactosidase （β-Gal） etc.
Colorectal cancer	Carcinoembryonic antigen （CEA）， lactate dehydrogenase （LDH）， microtubule-associated protein 1 light chain 3 beta （MAP1LC3B）， unc-51 like autophagy activating kinase 1 （ULK-1）， glutathione （GSH） etc.
Cardiovascular disease	Myoglobin （Myo）， cardiac troponin （cTn）， creatine kinase isoenzyme （CK-MB）， B-type natriuretic peptide （BNP）， growth differentiation factor 15 （GDF-15） etc.
Alzheimer's disease	Amyloid-β peptides （Aβ peptides）， tau protein， apolipoprotein E （apoE）， circulating free microRNAs （miRNAs）， alpha-1 antitrypsin （AAT）， Zn²⁺etc.
Inflammation	C-reactive protein （CRP）， serum amyloid A （SAA）， procalcitonin （PCT）， ferritin （SF）， reactive oxygen species （ROS） etc.

Table 1 Examples of universally acknowledged biomarkers and related diseases

Diseases	Biomarkers
Lung cancer	Carcinoembryonic antigen （CEA）， neuron specific enolase （NSE）， squamous cell carcinoma antigen （SCCA）， cytokeratin 19 fragment antigen （CYFRA21-1）， biothiols etc.
Liver cancer	Alpha fetoprotein （AFP）， alpha-L fucosidase （AFU）， hepatocyte growth factor （HGF） etc.
Gastric cancer	Carcinoembryonic antigen （CEA）， carbohydrate antigen （CA 19-9， CA72-4）， pepsinogen Ⅰ/Ⅱ（PG Ⅰ/Ⅱ） etc.
Breast cancer	Carcinoembryonic antigen （CEA）， carbohydrate antigen （CA）， tissue polypeptide specific antigen （TPS）， epithelial cadherin （E-cadherin）， alkaline phosphatase （ALP）， nitroreductase （NTR）， H₂S etc.
Cervical cancer	Carbohydrate antigen （CA125，CA72-4）， squamous cell carcinoma antigen （SCCA）， hepatocyte growth factor （HGF）， mixed lineage kinase domain-like protein （MLKL）， Cu²⁺， Hg²⁺etc.
Ovary cancer	Tumor necrosis factor-α （TNF-α）， humanepididymisprotein4 （HE4）， hexokinase2 （HK2）， sequestosome-1 （SQSTM1/p62），β-galactosidase （β-Gal） etc.
Colorectal cancer	Carcinoembryonic antigen （CEA）， lactate dehydrogenase （LDH）， microtubule-associated protein 1 light chain 3 beta （MAP1LC3B）， unc-51 like autophagy activating kinase 1 （ULK-1）， glutathione （GSH） etc.
Cardiovascular disease	Myoglobin （Myo）， cardiac troponin （cTn）， creatine kinase isoenzyme （CK-MB）， B-type natriuretic peptide （BNP）， growth differentiation factor 15 （GDF-15） etc.
Alzheimer's disease	Amyloid-β peptides （Aβ peptides）， tau protein， apolipoprotein E （apoE）， circulating free microRNAs （miRNAs）， alpha-1 antitrypsin （AAT）， Zn²⁺etc.
Inflammation	C-reactive protein （CRP）， serum amyloid A （SAA）， procalcitonin （PCT）， ferritin （SF）， reactive oxygen species （ROS） etc.

Fig.1 （A） The structure and response mechanism of AIE probe TPAPyP；（B） The fluorescence response of probe TPAPyP （100 μmol/L） after incubation with different analytes；（C） The fluorescence spectra of probe TPAPyP （100 μmol/L） after reaction with various concentrations of ALP；（D） The fluorescence imaging of HeLa cells and MDCK cells incubated with probe TPAPyP （2 μmol/L）；（E） The fluorescence imaging of HeLa cells （top） and MDCK cells （bottom） incubated with ROS probe DCFH［34］

Fig.2 （A） The structure and schematic illustration of intracellular response of AIE probe DQM-ALP；（B） The kinetic curves of probe DQM-ALP before and after response to ALP；（C） The fluorescence response of probe DQM-ALP （10 μmol/L） after incubation with different analytes；（D） The fluorescence imaging of HeLa cells incubated with probe DQM-ALP （10 μmol/L）；（E） Fluorescence imaging of liver tumor-bearing mice after injection of probe DQM-ALP （50 μmol/L）［35］

Fig.3 （A） The structure and schematic illustration of intracellular response of AIE probe QM-βgal；（B） The fluorescence spectra of probe QM-βgal （10 μmol/L） after reaction with various concentrations of β-Gal and corresponding linear relationship；（C） The fluorescence response of probe QM-βgal （10 μmol/L） after incubation with different analytes；（D） The fluorescence imaging of SKOV-3 cells incubated with probe QM-βgal （10 μmol/L）［37］

Fig.4 （A） The structure and response mechanism of AIE probe DCMCA-β-gal；（B） The linear relationship between the ratio-metric fluorescence intensity I676 nm/I550 nm of probe DCMCA-β-gal and the concentration of β-Gal；（C） Fluorescence imaging of ovarian tumor-bearing mice after injection of probe DCMCA-β-gal［38］

Fig.5 （A）The structure and response mechanism of AIE probe Gal-TPE-BT；（B） The fluorescence spectra of probe Gal-TPE-BT （10 μmol/L） after reaction with various concentrations of β-Gal；（C） The linear relationship between the ratio-metric fluorescence intensity I550 nm/I440 nm of probe Gal-TPE-BT and the concentration of β-Gal［39］

Fig.6 （A） The structure and schematic illustration of intracellular response of AIE probe ABT-Gal；（B） The fluorescence imaging of A549 cells and SKOV-3 cells incubated with probe ABT-Gal-1 （20 μmol/L）；（C） The linear relationship between the fluorescence intensity of probe ABT-Gal-1 and the concentration of β-Gal；（D） The fluorescence spectra of probe ABT-Gal-1 （10 μmol/L） after reaction with various concentrations of β-Gal［40］

Fig.7 （A） The structure and response mechanism of AIE probe Q-NO2；（B） The fluorescence spectra of probe Q-NO2 （10 μmol/L） after reaction with various concentrations of NTR and corresponding linear relationship；（C） Fluorescence imaging of breast tumor-bearing mice after injection of probe Q-NO2；（D） Fluorescence imaging of tumor-bearing mice after injection of probe Q-NO2［41］

Fig.8 （A） The structure and response mechanism of AIE probe CyNP；（B） Fluorescence imaging of breast tumor-bearing mice after injection of probe CyNP；（C） Photothermal imaging of breast tumor-bearing mice after injection of probe CyNP；（D） Photos of tumor in mice［42］

Fig.9 （A） The structure and response mechanism of AIE probe TPE（OH）-8HQ；（B） The fluorescence spectra of probe TPE（OH）-8HQ （10 μmol/L） after reaction with various concentrations of Zn2+；（C） The linear relationship between the fluorescence intensity of probe TPE（OH）-8HQ and the concentration of Zn2+；（D） The fluorescence response of probe TPE（OH）-8HQ （10 μmol/L） after incubation with different analytes；（E） The fluorescence imaging of HeLa cells incubated with probe TPE（OH）-8HQ （20 μmol/L）；（F） Fluorescence response of TPE（OH）-8HQ （1 mmol/L） to Zn2+ on test papers［47］

Fig.10 （A） The structure and response mechanism of AIE probe DHN；（B） The absorption spectra of probe DHN（10 μmol/L） before and after response to Zn2+；（C） The detection mechanism of PVA_DHN composite film；（D） Photos of DHN response to various concentrations of Zincovit under UV irradiation；（E） The fluorescence imaging of N2a cells incubated with probe DHN （5 μmol/L）［48］

Fig.11 （A） The design strategy of AIE probe Cm-o-TPA and Cm-p-TPA；（B） The normalized absorption spectra of Cm-o-TPA and Cm-p-TPA in tetrahydrofuran （THF） solution；（C） The fluorescence spectra of Cm-p-TPA in THF/H2O mixed solvent with different water fractions （fw）；（D） The lifetime changes of Cm-p-TPA NPs （10 μmol/L） in HeLa cells；（E） Monitoring of mitophagy process with Cm-p-TPA NPs （10 μmol/L）［51］

Fig.12 （A） The structure and response mechanism of AIE probe DPP；（B） The linear relationship between the relative fluorescence intensity I648 nm/I0 of probe DPP and the concentration of Cu2+；（C） The fluorescence response of probe DPP （20 μmol/L） after incubation with different analytes；（D） The fluorescence imaging of HeLa cells incubated with probe DPP（10 μmol/L）［52］

Fig.13 （A） The structure of AIE probe R1， R2， TPP-Cl and TPP-Br and response mechanism of TPP-Br；（B） The linear relationship between the fluorescence intensity of probe TPP-Br and the concentration of Hg2+；（C） The fluorescence response of probe TPP-Br （50 μmol/L） after incubation with different analytes in the presence of Hg2+ （30?μmol/L）；（D） The fluorescence imaging of HeLa cells incubated with probe TPP-Br （10 μmol/L）［57］

Fig.14 （A） The structure and response mechanism of AIE probe TPE-4TA；（B） The polyvinyl alcohol （PVA）-based hydrogel film dopped with TPE-4TA；（C） The fluorescence spectra of PVA-based hydrogel film after reaction with various concentrations of Hg2+；（D） The linear relationship between the fluorescence intensity of PVA-based hydrogel film and the concentration of Hg2+［58］

Fig.15 （A） The structure and response mechanism of AIE probe TBL；（B） The fluorescence spectra of TBL in dimethyl sulfoxide （DMSO）/H2O mixed solvent with different water fractions （fw）；（C） Chemiluminescence of luminol dots （1.2 mmol/L） and TBL dots （1.2 mmol/L） covered by a piece of approximately 3 mm thick pork ham in a H2O2/NaClO mixed solution；（D） The chemiluminescence imaging of mice after subcutaneous injection of TBL dots with H2O2 and NaClO；（E） The chemiluminescence imaging of breast tumor-bearing mice after injection of TBL dots［65］

Fig.16 （A） The structure and response mechanism of AIE probe TPE-N（Ph）-DBT-PH；（B） The chemiluminescence spectra of TPE-N（Ph）-DBT-PH；（C） The linear relationship between the chemiluminescence intensity of probe TPE-N（Ph）-DBT-PH and the concentration of 1O2；（D） The chemiluminescence response of probe TPE-N（Ph）-DBT-PH （10 μmol/L） after incubation with different analytes；（E） The chemiluminescence imaging of RAW 264.7 cells incubated with probe TPE-N（Ph）-DBT-PH；（F） The chemiluminescence imaging of a arthritismouse model after injection of TPE-N（Ph）-DBT-PH［66］

Fig.17 （A） The structure and response mechanism of AIE probe BTPAB；（B） The fluorescence spectra of BTPAB（10 μmol/L） after reaction with various concentrations of H2O2；（C） The linear relationship between the fluorescence intensity of BTPAB and the concentration of H2O2；（D） The fluorescence imaging of HeLa cells incubated with probe BTPAB；（E） Fluorescence response of BTPAB to H2O2 on TLC plates and corresponding linear relationship［69］

Fig.18 （A） The structure and response mechanism of AIE probe BTPE-NO2；（B） The fluorescence spectra of BTPE-NO2@F127 （BTPE-NO2 32.6?μg/mL） after reaction with various concentrations of H2O2；（C） The linear relationship between the fluorescence intensity of BTPE-NO2@F127 and the concentration of H2O2；（D） The fluorescence imaging of an interstitial cystitis mouse model after injection of BTPE-NO2@F127；（E） The fluorescence imaging of a trazodone-induced liver injury mouse model after injection of BTPE-NO2@F127；（F） The multispectral optoacoustic tomography imaging of a trazodone-induced liver injury mouse model after injection of BTPE-NO2@F127［70］

Fig.19 （A） The structure and response mechanism of AIE probe QY-N；（B） The fluorescence spectra of QY-N （10 μmol/L） after reaction with various concentrations of NO；（C） The linear relationship between the fluorescence intensity of QY-N and the concentration of NO；（D） The fluorescence imaging of livers incubated with probe QY-N；（E） The multispectral optoacoustic tomography imaging of livers after injection of QY-N［73］

Fig.20 （A） The structure and response mechanism of AIE probe BNDA；（B） The fluorescence imaging of an APAP-induced liver injury mouse model after injection of BNDA@HβCD；（C） The fluorescence imaging of an TSN-induce dliver injury mouse model after injection of BNDA@HβCD；（D） The fluorescence imaging of soybean sprouts［74］

Fig.21 （A） The structure and response mechanism of AIE probe DNBS-HCA；（B） The fluorescence spectra of DNBS-HCA after reaction with various concentrations of GSH， Cys and Hcy， repectively；（C） The linear relationship between the fluorescence intensity of DNBS-HCA and the concentration of GSH， Cys and Hcy， repectively；（D） The fluorescence imaging of PC-3 cells and A549 cells incubated with probe DNBS-HCA；（E） Fluorescence response of DNBS-HCA to Cys on test papers［77］

Fig.22 （A） The structure and response mechanism of AIE probe TPEPY-S-Fc；（B） The fluorescence imaging of CT-26 cells incubated with probe TPEPY-S-Fc；（C） The fluorescence spectra of 1O2 probe SOSG in the presence of TPEPY-S-Fc （20 μmol/L） and GSH （200 μmol/L）；（D） The time-dependent relative fluorescence intensity I530 nm/I0 of probe SOSG［78］

Fig.23 （A） The structure and response mechanism of AIE probe HBS-DNP；（B） The fluorescence spectra of HBS-DNP （10 μmol/L） after reaction with various concentrations of H2S；（C） The linear relationship between the fluorescence intensity of HBS-DNP and the concentration of H2S；（D） The fluorescence imaging of Hela cells incubated with probe HBS-DNP（10 μmol/L）［82］

Fig.24 （A） The structure and response mechanism of AIE probe TPA-M；（B） The fluorescence response of probe TPA-M （10 μmol/L） after incubation with different analytes；（C） The fluorescence spectra of TPA-M （10 μmol/L） after reaction with various concentrations of H2S and corresponding linear relationship；（D） The fluorescence response of probe TPA-M （10 μmol/L） after incubation with different analytes in the presence of H2S（300?μmol/L）；（E） The fluorescence imaging of MCF-7 cells incubated with probe TPA-M［83］

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Research Progress of Fluorescent Probes Based on Aggregation-Induced Emission for Detection of Biomarkers

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