The development of efficient aggregation-induced emission(AIE)active probes is crucial for disease diagnosis,particularly for tumors and cardiovascular diseases.Current AIE-active probes primarily focus on improving t...The development of efficient aggregation-induced emission(AIE)active probes is crucial for disease diagnosis,particularly for tumors and cardiovascular diseases.Current AIE-active probes primarily focus on improving their water solubility to resist aggregation,thereby achieving an initial fluorescence-off state.However,the complex biological environment can cause undesirable aggregation,resulting in false signals.To address this issue,we have ingeniously introduced an azo group into the AIE luminogen(AIEgen),developing a reductase-activated AIE probe,Azo-quinoline-malononitrile(QM)-PN,for imaging hypoxic environments.In this probe,the azo group promotes intramolecular motion through rapid E/Z isomerization,causing the excited state energy to dissipate via non-radiative decay,thus turning off the initial fluorescence.In the presence of reductase,Azo-QM-PN is reduced and cleaved to produce the hydrophobic AIEgen NH_(2)-QM-PN,which subsequently aggregates and generates an in situ AIE signal,thereby imaging the hypoxic environment with reductase.Encapsulation of Azo-QM-PN with DSPEPEG2000 results in the formation of the nanoprobe Azo-QM-PN NPs,which can effectively penetrate cell membranes,specifically illuminate tumor cells,monitor fluctuations in azo reductase levels,and deeply penetrate and image multicellular tumor spheroids,demonstrating potential for hypoxic tumor imaging.Additionally,the nanoprobe Azo-QM-PN NPs can selectively image hypoxic atherosclerotic plaque tissues,showing potential for detecting atherosclerosis.Therefore,in this study,we successfully developed an enzyme-activated AIE probe for imaging hypoxic environments,laying the foundation for further clinical applications.展开更多
Urinary microalbumin(mALB)serves as an exceptionally sensitive indicator for the early detection of kidney damage,playing a pivotal role in identifying chronic renal failure and kidney lesions in individuals.Neverthel...Urinary microalbumin(mALB)serves as an exceptionally sensitive indicator for the early detection of kidney damage,playing a pivotal role in identifying chronic renal failure and kidney lesions in individuals.Nevertheless,the currentfluores-cent methodologies for point-of-care(POC)diagnosis of mALB in real urine still exhibit suboptimal performance.Herein,the development and synthesis of QM-N2,an albumin-activated near-infrared(NIR)aggregation-induced emission(AIE)fluorescent probe,are presented.The strategic incorporation and positioning of quaternary ammonium salts within the quinoline-malononitrile(QM)scaffold sig-nificantly influence solubility and luminescence characteristics.Specifically,the quaternary ammonium salt-free variant,QM-OH,and the quaternary ammonium salt integrated at the donor function group(DFG)site,QM-N1,display limited solubility in aqueous solutions while demonstrating a distinctfluorescence signal.Conversely,the incorporation of quaternary ammonium salt at the conformational functional group(CFG)site in QM-N2 imparts superior dispersibility in water and reduces the initialfluorescence.Furthermore,the integration of a well-defined D-π-A struc-ture within QM-N2 enables itself with near-infrared emission,which is crucial for mitigating interference from autofluorescence present in urine samples.Upon inter-action with albumin,QM-N2 forms a tight bond with the IIA site of the subdomain of human serum albumin(HSA),inducing alterations in protein configuration and constraining the intrinsic motion offluorescent molecules.This interaction inducesfluorescence,facilitating the sensitive detection of trace albumin.Ultimately,QM-N2 is applied for POC testing of mALB using portable equipment,particularly in the diagnosis of mALB-related diseases,notably chronic renal failure.This positioning underscores its potential as an ideal candidate for self-health measurement at home or in community hospitals.展开更多
基金supported by the National Key Research and Development Program of China(2021YFA0910000)NSFC Excellent Young Scientist Scheme(22222803)+1 种基金the NSFC Science Center Program(21788102),NSFC(22408105)the China Postdoctoral Science Foundation(2022M72142).
文摘The development of efficient aggregation-induced emission(AIE)active probes is crucial for disease diagnosis,particularly for tumors and cardiovascular diseases.Current AIE-active probes primarily focus on improving their water solubility to resist aggregation,thereby achieving an initial fluorescence-off state.However,the complex biological environment can cause undesirable aggregation,resulting in false signals.To address this issue,we have ingeniously introduced an azo group into the AIE luminogen(AIEgen),developing a reductase-activated AIE probe,Azo-quinoline-malononitrile(QM)-PN,for imaging hypoxic environments.In this probe,the azo group promotes intramolecular motion through rapid E/Z isomerization,causing the excited state energy to dissipate via non-radiative decay,thus turning off the initial fluorescence.In the presence of reductase,Azo-QM-PN is reduced and cleaved to produce the hydrophobic AIEgen NH_(2)-QM-PN,which subsequently aggregates and generates an in situ AIE signal,thereby imaging the hypoxic environment with reductase.Encapsulation of Azo-QM-PN with DSPEPEG2000 results in the formation of the nanoprobe Azo-QM-PN NPs,which can effectively penetrate cell membranes,specifically illuminate tumor cells,monitor fluctuations in azo reductase levels,and deeply penetrate and image multicellular tumor spheroids,demonstrating potential for hypoxic tumor imaging.Additionally,the nanoprobe Azo-QM-PN NPs can selectively image hypoxic atherosclerotic plaque tissues,showing potential for detecting atherosclerosis.Therefore,in this study,we successfully developed an enzyme-activated AIE probe for imaging hypoxic environments,laying the foundation for further clinical applications.
基金National Key Research and Development Program of China,Grant/Award Number:2021YFA0910000NSFC,Grant/Award Numbers:22222803,91959202,21974047+1 种基金China Postdoctoral Science Foundation,Grant/Award Number:2022M72142Shanghai Municipal Science and Technology Major Project,Grant/Award Number:2018SHZDZX03。
文摘Urinary microalbumin(mALB)serves as an exceptionally sensitive indicator for the early detection of kidney damage,playing a pivotal role in identifying chronic renal failure and kidney lesions in individuals.Nevertheless,the currentfluores-cent methodologies for point-of-care(POC)diagnosis of mALB in real urine still exhibit suboptimal performance.Herein,the development and synthesis of QM-N2,an albumin-activated near-infrared(NIR)aggregation-induced emission(AIE)fluorescent probe,are presented.The strategic incorporation and positioning of quaternary ammonium salts within the quinoline-malononitrile(QM)scaffold sig-nificantly influence solubility and luminescence characteristics.Specifically,the quaternary ammonium salt-free variant,QM-OH,and the quaternary ammonium salt integrated at the donor function group(DFG)site,QM-N1,display limited solubility in aqueous solutions while demonstrating a distinctfluorescence signal.Conversely,the incorporation of quaternary ammonium salt at the conformational functional group(CFG)site in QM-N2 imparts superior dispersibility in water and reduces the initialfluorescence.Furthermore,the integration of a well-defined D-π-A struc-ture within QM-N2 enables itself with near-infrared emission,which is crucial for mitigating interference from autofluorescence present in urine samples.Upon inter-action with albumin,QM-N2 forms a tight bond with the IIA site of the subdomain of human serum albumin(HSA),inducing alterations in protein configuration and constraining the intrinsic motion offluorescent molecules.This interaction inducesfluorescence,facilitating the sensitive detection of trace albumin.Ultimately,QM-N2 is applied for POC testing of mALB using portable equipment,particularly in the diagnosis of mALB-related diseases,notably chronic renal failure.This positioning underscores its potential as an ideal candidate for self-health measurement at home or in community hospitals.
