Aptamer Applications in Neuroscience Part 1
May 27, 2024
Abstract:
Ua qhov tseem ceeb ua rau muaj kev tsis taus, cov kab mob neurological tau txais kev pom zoo los ntawm cov zej zog kev noj qab haus huv thoob ntiaj teb.
Lub paj hlwb yog ib feem tseem ceeb ntawm tib neeg lub cev. Nws yog lub luag haujlwm rau tib neeg kev xav, kev xav, kev txav, kev xav, thiab kev xav. Txawm li cas los xij, qee tus neeg yuav muaj teeb meem neurological uas cuam tshuam rau lawv lub cim xeeb. Cov kab mob hauv paj hlwb xa mus rau cov kev hloov pauv hauv lub hauv nruab nrab lub paj hlwb thiab lub paj hlwb peripheral, xws li mob stroke, Parkinson's disease, Alzheimer's disease, thiab lwm yam. Cov kab mob no yuav cuam tshuam rau kev nco, tab sis peb txhua tus tuaj yeem kov yeej lawv los ntawm txoj kev nquag. Txhim kho nws.
Thawj yog mob stroke. Raws li kev txheeb cais, ntau lab tus tib neeg raug cuam tshuam los ntawm kev mob stroke txhua xyoo, thiab ib qho ntawm cov tsos mob tshwm sim feem ntau yog kev nco. Stroke ua rau lub cev puas tsuaj heev vim nws cuam tshuam rau qhov chaw ntawm lub hlwb uas muab cov pa oxygen thiab ntshav. Txawm li cas los xij, peb tuaj yeem tiv thaiv kev mob stroke los ntawm kev tawm dag zog thiab hloov peb tus cwj pwm noj mov. Piv txwv li, kev tawm dag zog kom zoo, tswj lub cev hnyav thiab noj zaub mov zoo tuaj yeem txo qhov kev pheej hmoo ntawm mob stroke thiab yog li khaws cia zoo dua.
Tom ntej no yog tus kab mob Parkinson. Qhov no yog tus kab mob txav mus los los ntawm kev tuag ntawm cov neurons. Ntxiv nrog rau kev txav mus los, tus kab mob Parkinson tuaj yeem cuam tshuam kev nco. Cov kev tshawb fawb pom tau tias cov neeg mob feem ntau tsim kev puas hlwb, nrog rau kev nco tsis tau. Txawm li cas los xij, cov neeg mob tuaj yeem siv ntau yam kev ntsuas los ncua kev loj hlob ntawm tus kab mob, xws li tau txais kev kho mob tsis tu ncua thiab kev cob qhia kev kho mob. Muaj kev nyiam ua xws li mloog suab paj nruag, nyeem ntawv, thiab kawm cov txuj ci tshiab kuj tseem tuaj yeem muaj txiaj ntsig zoo rau kev so lub hlwb thiab pab kev nco qab.
Thaum kawg, muaj Alzheimer's disease. Nws yog ib yam kab mob uas ua rau muaj kev puas siab puas ntsws, nrog rau kev nco tsis tau yog ib qho ntawm cov tsos mob pom tseeb tshaj plaws. Txawm li cas los xij, Alzheimer's disease kuj yog ib yam kab mob uas tuaj yeem raug tshem tawm. Kev tshawb fawb qhia tau hais tias kev tawm dag zog, noj zaub mov noj qab haus huv, kawm txuj ci tshiab, thiab kev ua haujlwm pub dawb tuaj yeem pab txo qis kev kis tus kab mob thiab txhim kho kev nco.
Peb yuav tsum nco ntsoov ua tus cwj pwm zoo thiab siv txoj hauv kev los tiv thaiv thiab kho cov kab mob neurological los txhim kho peb lub cim xeeb. Txawm hais tias peb raug cuam tshuam los, peb tuaj yeem siv ntau yam kev ntsuas los txhim kho peb txoj kev tiv thaiv thiab muaj peev xwm tiv thaiv tus kab mob. Tsuav yog peb pheej niaj hnub ua, peb yuav nrhiav tau txoj hauv kev zoo dua, kev noj qab haus huv los tiv thaiv thiab kho kev nco. Nws tuaj yeem pom tias peb yuav tsum txhim kho kev nco, thiab Cistanche deserticola tuaj yeem txhim kho kev nco zoo vim Cistanche deserticola yog cov khoom siv tshuaj hauv Suav teb uas muaj ntau yam teebmeem, ib qho ntawm kev txhim kho kev nco. Kev ua tau zoo ntawm Cistanche deserticola los ntawm ntau yam khoom xyaw uas nws muaj, suav nrog tannic acid, polysaccharides, flavonoid glycosides, thiab lwm yam. Cov khoom xyaw no tuaj yeem txhawb lub hlwb kev noj qab haus huv los ntawm ntau txoj hauv kev.
Nyem Paub txhawm rau txhim kho lub cim xeeb luv luv
Ntau tshaj li ib lab tus tib neeg raug kev txom nyem los ntawm ib qho ntawm cov kab mob hauv qab no: dementia, qaug dab peg, mob stroke, migraine, meningitis, Alzheimer's disease, Parkinson's disease, ntau yam sclerosis, amyotrophic lateral sclerosis, Huntington's disease, priondisease, los yog mob hlwb. Cov kev kuaj mob thiab kev kho mob tsuas yog txwv rau ntau yam kab mob no.
Aptamers, ua me me thiab tsis-immunogenic nucleic acid molecules uas yooj yim rau chemicallymodify, muaj peev xwm kuaj xyuas thiab theragnostic daim ntawv thov kom tau raws li cov kev xav tau no.
Qhov kev tshuaj xyuas no nthuav tawm cov kev tshawb fawb pioneering hauv kev thov cov aptamers, uas qhia cov lus cog tseg rau kev kuaj mob yav tom ntej thiab kev kho mob ntawm cov hlab ntsha uas ua rau muaj teeb meem kev noj qab haus huv thoob ntiaj teb.
Ntsiab lus: Aptamer; neuroscience; kab mob neurological; neurological mob; neurotoxins; mob qog noj ntshav.
1. Taw qhia
Aptamers yog ib leeg-stranded DNA, RNA, los yog hluavtaws XNA molecules uas muaj peev xwm foldinto cim peb-dimensional (3D) cov qauv uas lawv khi lawv lub hom phiaj molecules nrog siab tshwj xeeb thiab affinity [1,2].
Ib txoj hauv kev los xaiv aptamers tau ua tiav xyoo 1990 los ntawm peb pawg sib cais [3–5]. Txoj kev tam sim no hu ua Systematic Evolutionof Ligands los ntawm Exponential Enrichment (SELEX). Txij thaum ntawd los, ntau cov aptamers tau raug xaiv los siv rau hauv cov cheeb tsam ntawm cov kev tshawb fawb yooj yim thiab ntau cov aptamers yog qhov tsis zoo rau kev siv hauv kev kho mob, kev kuaj mob, thiab kev kos duab [6–10].
Txoj kev SELEX simulates Darwinian evolution hauv vitro. Nws suav nrog ntau qhov kev xaiv ib puag ncig, thiab, tom qab txhua qhov hloov pauv, kev nthuav dav ntxiv ntawm "fittest" oligonucleotides (oligos) yog ua tiav.
Ib puag ncig ntawm SELEX ib txwm muaj xws li peb kauj ruam hauv kev txiav txim (1) incubate lub hom phiaj xav tau molecule nrog lub pas dej ua ke ntawm oligos nrog lub hauv paus 20-60 nucleotide cheeb tsam ntawm randomized ib puag ncig los ntawm lub davhlau ya nyob twg cheeb tsam ntawm qhov tsis tu ncua uas yuav yog cov qauv rau tom qab polymerase saw cov tshuaj tiv thaiv (PCRs ), (2) ntes cov oligos hauv lub pas dej ua ke uas ua tiav khi lub hom phiaj, thiab (3) nthuav tawm cov oligos raug ntes los ntawm PCR lossis thim rov qab-PCR (rt-PCR), nyob ntawm seb hom oligo, DNA lossis RNA feem.
Rounds ntawm counter-xaiv kuj suav nrog, nyob rau hauv uas lub pas dej nucleic acid tau dhau los ntawm qhov tsis muaj kev txhawb nqa matrix, tsis muaj lub hom phiaj xav tau lossis dhau qhov kev txhawb nqa matrix nrog ib lossis ntau dua lwm cov molecules uas yuav muaj feem cuam tshuam rau lub hom phiaj molecule.
Hauv kev xaiv xaiv, cov oligos uas tsis khi cov kev txhawb nqa matrix lossis cov qauv muaj feem xyuam nrog cov molecules raug ntes thiab txuas ntxiv mus rau ntau qhov ntawm SELEX.
Counterselection yog ua rau ntau lub hom phiaj, xws li tshem tawm oligos uas cuam tshuam nrog (1) lub matrix txhawb, (2) analogs los yog molecules uas muaj feem xyuam rau lub hom phiaj, los yog (3) molecules tam sim no nyob rau hauv siab concentrations nyob rau hauv cov roj ntsha matrix (xws li cov ntshav. los yog cov ntaub so ntswg extract) nyob rau hauv uas xaiv aptamerwill ua haujlwm.
Lub hom phiaj tseem ceeb ntawm kev xaiv cov kev xaiv-kev xaiv yog kom nce aptamer tshwj xeeb rau cov phiaj xwm thedesired tshaj lwm cov peev txheej molecular. Dhau li ntawm cov qauv SELEX, nyuam qhuav tsim qauv-hloov SELEX tau dhau los ua neeg nyiam [11–13].
Hauv txoj hauv kev no, oligos yuav tsum tau hloov pauv lawv cov qauv thaum lawv cuam tshuam nrog lub hom phiaj, kom tsis txhob cuam tshuam los ntawm kev sib koom ua ke ntawm kev ntes. Qhov no ua kom ntseeg tau tias cov xaiv aptamers hloov pauv hauv cov qauv raws li ligand binding. Lwm txoj hauv kev SELEX tau tsim muaj xws li CE-SELEX, Cell-SELEX, thiab hauv-vivo SELEX, raws li tau piav qhia hauv Daim duab 1.
Nws yog qhov ua tau los ua ke cov txheej txheem SELEX sib txawv los tsim cov txheej txheem nyuaj dua. Tom qab aptamers raug xaiv los ntawm SELEX, lawv tau hloov kho ntxiv los txhim kho lawv qhov tshwj xeeb thiab kev sib raug zoo los ntawm ntau txoj hauv kev uas, hauv toto, tuaj yeem hu ua kev loj hlob.
Muaj ntau qhov kev txiav txim siab hauv kev xaiv thiab loj hlob aptamers. Ua ntej, cov qauv ntawm aptamers thiab aptamer-target kev sib cuam tshuam yog cuam tshuam los ntawm qhov kub thiab txias thiab cov khoom tsis haum, suav nrog ions, ionic zog, thiab pH.
Yog li, ib qho ntawm cov ntsiab lus tseem ceeb tshaj plaws hauv SELEX tsim yog ua raws li ib puag ncig (biological matrix lossis ntsev / buffercomposition) thaum xaiv qhov pom ntawm aptamer molecular lub hom phiaj thiab kev sib cuam tshuam ntawm aptamer thiab lub hom phiaj yuav tshwm sim.
Xaiv qhov tsim nyog tsis muaj qhov sib xyaw thiab qhov kub thiab txias yuav ua kom pom kev ua haujlwm zoo ntawm cov aptamers xaiv nyob rau hauv cov xwm txheej uas lawv yuav siv [4,30–32].
Qhov thib ob, aptamer stability tej zaum yuav tsum tau txhim kho, raws li DNA thiab RNA aptamers yog lub hom phiaj rau nucleaseattacks. Qhov no yog qhov tshwj xeeb tshaj yog rau RNA, vim yog pawg 20OH, uas yog siv byribonucleases hauv kev tawm tsam electrophilic ntawm phosphate ntawm nucleic acid qaum rau hydrolysis.
Yog li, RNA yog labile rau qhov kub thiab txias ntau dua li DNA. Aptamerscan tuaj yeem ua tiav los ntawm kev hloov kho tshuaj tom qab xaiv los kov yeej qhov kev cuam tshuam no.Txawm li cas los xij, cov kev hloov kho no tuaj yeem ua rau lub aptamer poob qhov tshwj xeeb thiab / lossis kev sib raug zoo.
Yog li ntawd, feem ntau nws yog qhov zoo dua los suav nrog hloov kho nucleotides thaum SELEX. Muaj ntau qhov kev hloov kho uas ua tau Aptamer tau teev nyob rau hauv Table 2.
Aptamers tuaj yeem xaiv tau uas xaiv khi feem ntau cov kab mob, hlwb, kab mob, cov proteins, cov tshuaj lom, thiab peptides nrog cov affinities siab [45–48]. Lawv tuaj yeem siv tau ntau zaus yam tsis muaj kev cuam tshuam txog kev ua haujlwm. Hauv lwm lo lus, lawv tuaj yeem raug cais tawm ntawm lawv lub hom phiaj rau kev siv ntxiv.
Los ntawm qhov sib txawv, cov tshuaj tiv thaiv tsuas tuaj yeem siv tau ob peb zaug ua ntej lawv ua haujlwm. Nucleic acid aptamers tuaj yeem ua kom tiav kom ruaj khov dua li cov tshuaj tiv thaiv kab mob thiab cov enzymes, tshwj xeeb tshaj yog nyob rau qhov kub siab [2].
Ntxiv mus, ib zaug cov txheej txheem ntawm ib qho aptamer paub, nws cov tshuaj synthesis thiab purification rau homogeneity yog heev reproducible thiab pheej yig. Cov khoom no muab aptamers lub peev xwm tosubstitute rau cov tshuaj tiv thaiv raws li cov khoom ntawm cov ntsuas ntsuas [49].
Qhov yooj yim ntawm aptamers'structures thiab lawv lub peev xwm "daim npog" thaj tsam ntawm ib qho kev sib txuas ntawm aptamer nrog kev sib txuas ntawm kev sib txuas ua ke muab cov kev xaiv rau cov teeb liab uas tso cai rau kev sib koom ua ke ntawm aptamers rau hauv ntau lub platforms, uas tsis tuaj yeem hloov kho rau cov tshuaj tiv thaiv. Cov khoom no motivateaptamer-based biosensor kev txhim kho [50–52].
Tsim cov cuab yeej tshiab rau kev kuaj mob yog ib qho ntawm qhov tseem ceeb tshaj plaws hauv biosensorfield, nrog ntau tus neeg tshawb nrhiav nrhiav los tsim cov txheej txheem yooj yim, ua tau zoo, thiab pheej yig dua kom ua tiav kev kuaj mob ntxov thiab cov tshuaj precision.
Kev suav nrog aptamers hauv biosensors (lub npe "aptasensors") tau pib hauv xyoo 1990.
Ib qho piv txwv thaum ntxov ntawm aptamers raws li biorecognition ntsiab yog ib qho kho qhov muag biosensor uas siv fluorescently sau npe aptamersaginst tib neeg neutrophil elastase hauv ib homogenous assay [53].
Txij thaum ntawd los, ntau hom kev tsim qauv ntawm aptasensor tau tshaj tawm, feem ntau nrog aptamers ntawm cov khoom txhawb nqa, thiab nrog electrochemical, optical, mechanical, thiab acoustic signals [45,54–56]. Qee qhov piv txwv tau tham tom qab hauv kab lus no.
Aptamers kuj tau siv rau hauv kev kho mob. Kev hloov kho uas ua rau muaj kev nce ib nrab ntawm lub neej thiab txhim kho pharmacokinetics ua rau qee qhov kev xaiv zoo rau kev siv tshuaj kho mob. Piv nrog rau cov tshuaj tiv thaiv kab mob, aptamers muaj tsawg dua cov tshuaj tiv thaiv kab mob, thiab lawv cov kev ua tuaj yeem cuam tshuam los ntawm kev thim rov qab ntxiv oligonucleotides (Munzar li al., 2019).
Cov yam ntxwv tseem ceeb no pom zoo rau aptamers rau kev loj hlob raws li kev kho mob.Macugen (pegaptanib sodium), uas tau xaiv paub txog vascular endothelial growthfactor (VEGF), yog thawj aptamer tau pom zoo ua tus neeg sawv cev kho (Tobin, 2006).
Txij thaum ntawd los, ob peb aptamers tau mus txog ntau theem ntawm kev sim tshuaj nyob rau hauv uas lawv tab tom sim kho cov mob xws li mob ntsws cancer me me, von Willebrandfactor-txog teeb meem, angiomas, thiab lub raum cell carcinomas [51,57–60].
Lwm qhov kev siv tshuaj kho tau zoo ntawm aptamers suav nrog cov tshuab xa khoom [61,62].Ua kom tau txais txiaj ntsig zoo hauv cov tshuab no, aptamers yuav tsum paub cov cell nto proteins hauv lawv cov ntaub ntawv ib txwm muaj.
Cell-SELEX tau tsim los xaiv tawm tsam cell-surface proteins uas nquag nyuaj rau purify hauv lawv haiv neeg cov ntaub ntawv [63]. Ib qho aptamer uas paub txog acell nto protein tuaj yeem coopt tus receptor rau internalize cov khoom thauj mus rau lub aptamer.Nrog rau txoj kev no, ib tug tuaj yeem xaiv aptamers rau receptors feem ntau qhia ntawm ib leeg celltype uas tuaj yeem tsom rau hauv vivo [57].
Piv txwv li, anti-PSMA (prostate-specific membraneantigen) aptamers tau tsim los rau kev xa cov siRNAs rau cov qog nqaij hlav hauv nas lossis kab mob hlwb [62,64–66].
Hauv neuroscience, kev siv aptamers muaj, txog tam sim no, tau txwv, txawm hais tias thaum muaj ntau yam kev siv peev xwm. Aptamers tau tshaj tawm tias muaj kev xaiv kho mob rau cov kab mob neurodegenerative uas ua rau poob ntawm lub hauv paus paj hlwb (CNS) cov qauv thiab kev ua haujlwm, suav nrog Alzheimer's disease (AD), Parkinson'sdisease (PD), Creutzfeldt-Jakob kab mob, cov kab mob neuron lub cev muaj zog, thiab Huntington's. kab mob (HD) (Daim duab 1). Tam sim no, nyob ib ncig ntawm 50 lab tus tib neeg hauv ntiaj teb ntsib teeb meem dementia, uas tus nqi kho mob thoob ntiaj teb yog ze rau ib lab lab daus las hauv ib xyoos.
Qhov no ua rau dementias yog ib qho teeb meem loj tshaj plaws kho mob thiab nyiaj txiag rau peb lub neej [67]. Ib yam li ntawd, raws li United Nations thiab Lub Koom Haum Saib Xyuas Kev Noj Qab Haus Huv Hauv Ntiaj Teb, cov pej xeem hauv ntiaj teb muaj hnub nyoog tshaj 65 xyoo kwv yees yuav nce ob npaug los ntawm 2050.
Yog li ntawd, hnub nyoog-dependent kab mob neurodegenerative yuav tsum tau nce kev siv nyiaj rau kev kuaj mob thiab kev kho mob [67].
Cov kev xav tau tseem ceeb no los pab txhawb kev kuaj mob ntxov thiab kev siv tshuaj kho tshiab tuaj yeem ntsib byaptamers, uas tuaj yeem yog cov kev daws teeb meem rau qee qhov teeb meem hauv qab [68,69].
Aptamers tau tsim los rau cov ntawv thov hauv lub hlwb kev yees duab (MRI, PET, thiab lwm yam), neurotransmitter visualization, kuaj mob, thiab kev kho mob rau lub hlwb hlav thiab lwm yam kab mob hauv lub hlwb. Hauv ntau txoj hauv kev no, aptamers tau sau npe nrog cov khoom siv hluav taws xob, xws li fluorine -18 rau PET duab [70]. Hauv qhov kev tshuaj xyuas no, peb yuav tham txog kev ua tiav thiab cov teeb meem ntawm kev siv aptamers rau lub hlwb duab thiab cov kab mob neural.
2. Kev kuaj xyuas Molecular
2.1. Kev Tshawb Nrhiav Neurotoxin
Neurotoxins yog ib pab pawg neeg sib txawv ntawm cov tshuaj pharmacologically active compounds.Lawv siv cov tshuaj lom neeg muaj txiaj ntsig zoo rau lub paj hlwb ntawm cov kab mob, tab sis txawv ntawm lawv cov qauv tshuaj thiab cov txheej txheem ntawm kev ua.
Lawv hloov qhov kev ua tau zoo, thiab cuam tshuam nrog kev sib kis ntawm cov hlab ntsha impulses. Txhawm rau ntsuas lawv cov kev pheej hmoo rau tib neeg kev noj qab haus huv thiab kev cuam tshuam ib puag ncig, nws yog ib qho tseem ceeb uas yuav tsum tau siv cov txheej txheem rhiab txaus rau lawv qhov kev txheeb xyuas tseeb.
Nucleic acid aptamers tau siv los ua pov thawj tias muaj cov co toxins hauv cov dej thiab cov qauv tshuaj lom neeg nrog kev nkag siab zoo thiab kev xaiv [71]. Cov kev tshawb fawb tau tshaj tawm tias ua kom pom qhov tseeb ntawm botulinum neurotoxins (Botulinum A, E), saxitoxin, brevotoxin, paraquat, thiab tetrodotoxinby aptasensors.
Botulinum neurotoxins (BoNTs) yog ib qho ntawm cov kab mob neurotoxins uas tuag taus tshaj plaws thiab tuaj yeem ua haujlwm los ua cov neeg ua phem rau bioterrorism. Txhawm rau hais txog qhov xav tau tseem ceeb rau qhov kev xav tau, muaj txiaj ntsig zoo, thiab lub sijhawm tshawb nrhiav lub sijhawm tiag tiag rau BoNTs, sol-gel-based SELEX tau siv toisolate DNA aptamers tawm tsam botulinum neurotoxin hom E (BoNT-E) [47].
Cov aptamercandidate sequences, tom qab lub thib tsib puag ncig, tau soj ntsuam los ntawm cov tiam tom ntej sequencing (NGS), thiab high-frequency aptamers tau characterized. Hauv cov tsev neeg aptamer no, aptamerBT5.6 tau pom muaj kev sib raug zoo siab, ntawm 53 nM Kd, rau BoNT-E thiab tau immobilized ntawm lub platform grapheneoxide. Lub sensor no tau tso tawm ib qho 0.83 nM txwv kev kuaj pom (LoD) rau BoNT-E.
Brevotoxins (BTXs) thiab saxitoxins yog marine neurotoxins uas ua rau neurologicalshellfish lom (NSP). BTXs yog tus cwj pwm los ntawm kev mob toxicity siab thiab pib sai ntawm NSP.Technical teeb meem cuam tshuam nrog lawv cov kev tshuaj ntsuam tau txhawb cov kws tshawb fawb los tshawb nrhiav lwm txoj hauv kev, ua tau zoo, thiab pheej yig nrhiav txoj hauv kev rau cov neurotoxins muaj zog.
Rau lub hom phiaj no, ib qho electrochemical aptasensor tau tsim los kuaj BTX-2, rau cov uas tau xaiv DNA aptamers yog tus cwj pwm siv electrochemical impedance spectroscopy (EIS) thiab fluorescence.
Lub aptamer BT10, nrog rau kev sib raug zoo ntawm 42 nM rau BTX-2, tau muab tso rau hauv daim ntawv lo-dawb kev sib tw impedimetric biosensor uas pom tau tias muaj kev txwv tsis pub dhau 95 pM ntawm BTX-2.
Qhov aptasensor no tuaj yeem ntes BTX -2 nyob rau hauv lub plhaub plhaub ntses uas muaj cov lus teb txhim khu kev qha nyob rau hauv lub xub ntiag ntawm shellfish matrix [72]. Raws li cov chav kawm thib ob ntawm marine neurotoxins, saxitoxin yog tus cwj pwm rau pej xeem kev noj qab haus huv tseem ceeb.
Novelstudies yuav tsum tau tsim los ua lwm txoj hauv kev tsim nyog vim yog cov teeb meem technical thiab kev coj ncaj ncees ntawm cov tshuab siv tam sim no. Txhawm rau daws qhov xav tau no, ib daim ntawv lo-dawb opticalbiolayer interferometry kev sib tw aptasensor tau tsim. Lub biosensor muaj qhov txwv tsis pub tshaj 1.66 nM rau saxitoxin, nrog rau qib siab ntawm kev xaiv thiab rhiab heev, ruaj khov, thiab muaj peev xwm nrhiav tau sai [73].
Zoo ib yam li cov co toxins hauv hiav txwv, cov neurotoxins tso tawm raws li cov nab npawb ntawm cov co toxins uas muaj zog tshaj plaws thiab tuag taus. Hmoov tsis zoo, cov kev kuaj pom tus nab nab raws li kev soj ntsuam ntawm cov ntshav coagulation thiab cov tsos mob hauv chaw kho mob tsis tuaj yeem muab kev kuaj mob kom raug. Tsis tas li ntawd, batch-dependent variations ntawm antibody kev ua haujlwm nyuaj rau lawv siv hauv kev kuaj mob.
Ib tug high-affinity truncated version ntawm ib tug -Tox-FL aptamer, Ameslikas xaiv tawm tsam bungarotoxin ntawm Bungarus multicinctus (-Tox-T2) nrog ib tug ntau affinity (Kd=2.8 nM) tshaj cov niam txiv -Tox-FL (18 nM), tau siv rau hauv enzyme-linked aptamer assay format.
Hauv qhov teeb tsa no, -Tox-T2 aptamer tuaj yeem kuaj pom -toxin tsawg li 2 ng ntawm crude venom, uas pom tau tias nws muaj peev xwm rau Bungarus caeruleus venom detection [74].
2.2. Kev Tshawb Nrhiav Neurotransmitter
Txhawm rau tshawb xyuas qhov ua haujlwm nyuaj ntawm lub hlwb, kev saib xyuas cov neurotransmitteractivities thiab cov kev taw qhia yuav siv tau. Neurotransmitters yog qhov tseem ceeb rau cov ntaub ntawv hloov pauv ntawm cov hlwb thiab ua lub luag haujlwm tseem ceeb hauv kev mob hlwb xws li qaug dab peg, Parkinson's disease (PD), thiab Alzheimer's disease (AD).
Hauv ntau qhov kev tshawb fawb, aptamersspecific rau dopamine, epinephrine, los yog serotonin tau siv los tsim aptamer-based biosensors rau neurotransmitter nrhiav pom, hauv vivo thiab hauv vitro [75].
Ib qho catecholamine neurotransmitter, dopamine (DA) tswj cov yam ntxwv ntawm tib neeg cov metabolism, thiab cov hlab plawv, thiab lub raum ua haujlwm. Ntau cov kab mob neurodegenerative, tshwj xeeb tshaj yog PD, tau pom tias muaj kev cuam tshuam ncaj qha nrog cov metabolism hauv DA [76].
Yog li, tsim kom muaj kev nkag siab zoo thiab xaiv biosensors rau kev txiav txim siab DA yog ib qho tseem ceeb hauv cov kab mob. Thawj RNA aptamer tawm tsam DA, dopa2, khi DA nrog ib qho affinityrepresented los ntawm Kd=2.8 nM [77].
Siv cov aptamer no, ib daim ntawv lo-dawb electrochemical aptasensor raws li graphene-polyaniline composite zaj duab xis tau ntse kuaj pom muaj DA cov ntshav tsis zoo, nrog rau LoD ntawm 1.98 pM [78]. Hauv kev tshawb fawb tsis ntev los no, lwm qhov DA aptasensor tau tsim los ntawm DNA aptamer ua lub sensor thiab cov nyom carp daim tawv nqaij collagen graphene oxide (GCSC-GO) composite li transducer.
Cov khoom sib xyaw tau npaj los ntawm viaultra-sonication thiab tus cwj pwm los ntawm infrared (IR) thiab Raman spectroscopy, atomic forcemicroscopy, thiab EIS. Qhov system no suav nrog aptamer immobilization rau collagen tom qab sib txawv pulse voltammetry.
Txawm hais tias tus aptasensor tau pom qhov siab dua LoD ntawm 0.75 nM, piv rau lub sensor ua ntej nrog 2 pM, nws pom tau tias muaj kev xaiv siab rau DA cov sib txuas sib txuas ntau dhau thiab ntsuas DA kom raug nyob rau hauv muaj 10% ntshav qab zib [79].
Rau kev tsom xam ntawm ntau yam molecules nrog dawb-daim ntawv lo, siab rhiab heev, thiab xaiv, ib tug microcantilever array sensor nrog aptamers tsis ntev los no tau tshaj tawm. Lub sensor muaj ib tug array ntawm 12 microcantilevers hloov nrog thiolated DA aptamers thiab siv goldnanoparticles (AuNP) conjugated nrog ib tug stretch ntawm DNA uas yog complementary rau DAaptamer ntawm lub microcantilever nto.
Thaum xub thawj hybridized nrog DA aptamer, theAuNP-DNA conjugates raug tso tawm thaum lub aptamer khi DA, uas txhim kho qhov kev ntxhov siab ntawm cov array li ntawm 15 zaug thiab nce deflection.
Lub kaw lus muaj cov lus teb alinear hauv thaj tsam ntawm 0.5 mus rau 4 µM ntawm DA nrog LoD ntawm 77 nM. Nws qhov tshwj xeeb tau tshwm sim nrog 12 cov qauv thiab kev ua haujlwm zoo xws li L-DOPA, tsis muaj qhov pib deflections [80].
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