| Alzheimer's Disease(AD),also known as primary dementia,is an incurable,progressive,fatal chronic neurodegenerative disorder.With the advance of medicine,aging populations grows significantly in many countries around the world.While the possibility of developing AD raises with age,approaching 50%of the elderly beyond 85 are AD sufferers.The early definite diagnosis of AD can enable patients to have more treatment options,such as treatment strategies to reduce neuronal loss,or even help develop treatments that can prevent or completely cure the disease.However,despite the increasing incidence of AD,due to the early onset of AD symptoms such as short-term memory loss,behavioral changes,etc.are often associated with normal signs of aging in the human body,there is still a lack of effective diagnostic tools for the early stages of this disease.At present,the mainstream hypothesis about the pathogenic mechanism of AD is the amyloid protein hypothesis,the accumulation of ?-amyloid protein(A?)with neurotoxicity is considered as the main pathogenic factor.Therefore,the detection method of AD is mainly to label A? in brain tissue,cerebrospinal fluid,or blood.To date,the development of A? imaging probes has been very pervasive,where the content of A? is usually assessed by spectrophotometric determination of A? binding dyes.Traditional Ap binding dyes include thioflavin-T(ThT)and other benzothiazole derivatives,which exhibit high affinity for A?.However,their drawbacks are also obvious,such as weak fluorescence signal,large overlap with tissue autofluorescence,low signal to noise ratio,etc.In addition,prone to photobleaching,ThT and other derivatives can only be imaged in a short time.In order to make up for the deficiency of traditional imaging probes,we designed quantum dots as the main carrier of probes.Quantum dots have excellent optical properties such as optional emission wavelength,wide excitation spectrum,narrow and symmetrical emission spectrum,large Stokes shift,strong light stability,long fluorescence lifetime,and the biocompatibility of modified quantum dots is good too.These features make QDs an excellent alternative to traditional organic dyes.Based on the above background,a new QD-PEG-BTA probe was designed and synthesized for the early diagnosis of AD in this paper.Also,its structure,properties and detection effect on A? were characterized.The details are described as follows:(1)A novel QD-PEG-BTA probe was designed and synthesized using quantum dot(QD)as a core,polyethylene glycol(PEG)as an improvement material,and 2-(4-(6-methoxybenzo[d]thiazol-2-yl)phenylaminoethanol(BTA)as the target group.The structure of the probe was verified by NMR and MS.(2)A series of physical and chemical characterizations of quantum dot probes were performed.The size of the probes was measured by dynamic light scattering spectroscopy.The optical properties of the probes were characterized by UV-Vis absorption spectra and fluorescence emission spectra.It was verified that the size and the main optical properties of the probe were confirmed by quantum dots.(3)Quantum dot probes were subjected to a series of biological tests.Using fluorescence microscopy,TEM,and fluorescence spectroscopic analysis,the probes were compared with other materials in brain tissue,artificial cerebrospinal fluid,etc.and it was confirmed that the probes can be used for A?(1-40)testing,and the detection sensitivity is more than four orders of magnitude times that of BTA and ThT. |
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