雙色納米泡增強炎癥的生物發(fā)光成像摘要：

炎癥是許多嚴重疾病的關鍵因素。為了更好地理解炎癥發(fā)展的機制和提高疾病的診斷準確性，生物發(fā)光成像技術日益成為一種重要的工具。然而，由于缺乏靈敏和特異性標記劑，這種技術的應用存在一些挑戰(zhàn)。本文介紹了一種新型雙色納米泡，能夠通過增強炎癥的生物發(fā)光信號來提高成像的靈敏度。此外，利用基因工程技術基于生物體外抗原（apoptoticcellphagocytosisstimulated，ACPS）設計的雙色納米泡，可以實現(xiàn)更準確的炎癥成像。我們證明這種新型雙色納米泡對炎性細胞具有高度特異性，且具有較低的毒性和良好的生物相容性。因此，這種新型雙色納米泡具備了良好的應用前景，可用于更好地理解和治療炎癥相關疾病。

關鍵詞：

雙色納米泡，生物發(fā)光成像，炎癥，特異性標記劑，生物體外抗原（apoptoticcellphagocytosisstimulated，ACPS）。

Introduction:

Inflammationisthekeyfactorinmanyseriousdiseases.Inordertobetterunderstandthemechanismsofinflammationdevelopmentandimprovetheaccuracyofdiseasediagnosis,bioluminescenceimagingtechnologyisbecominganincreasinglyimportanttool.However,duetothelackofsensitiveandspecificlabelingagents,theapplicationofthistechnologyhassomechallenges.Inthispaper,weintroduceanewtypeofdual-colornanobubblethatenhancesthebiologicalluminescencesignalofinflammationtoimproveimagingsensitivity.Inaddition,usinggeneticengineeringtechnologybasedontheapoptoticcellphagocytosisstimulated(ACPS),adual-colornanobubbleisdesigned,whichcanachievemoreaccurateinflammationimaging.Wedemonstratethatthisnewtypeofdual-colornanobubblehashighspecificityforinflammatorycells,withlowtoxicityandgoodbiocompatibility.Therefore,thisnewtypeofdual-colornanobubblehasgoodapplicationprospectsandcanbeusedtobetterunderstandandtreatinflammation-relateddiseases.

Methods:

Thedual-colornanobubbleswerepreparedbylayer-by-layerassemblyofcationicandanionicpolyelectrolytes.Thesurfacemodificationofnanobubblesfunctionalizedwithantibodiescouldbedetectedbyfluorescencemicroscopyorflowcytometry.Cellularuptakeofthedual-colornanobubbleswasdeterminedbyconfocalmicroscopy.Theinflammatoryresponseswereevaluatedbyfluorescencemicroscopyandflowcytometry.Thetoxicityandbiocompatibilityofthedual-colornanobubbleswereevaluatedbyMTTassayandsubcutaneousinjection.

Results:

Wesuccessfullypreparedanewtypeofdual-colornanobubblethatenhancesthebiologicalluminescencesignalofinflammationtoimproveimagingsensitivity.Throughfluorescencemicroscopyandflowcytometry,wefoundthatthedual-colornanobubbleshavehighspecificityforinflammatorycells.Furthermore,thedual-colornanobubbleshavelowtoxicityandgoodbiocompatibility,suggestingagoodapplicationprospectforinflammation-relateddiseases.

Conclusion:

Insummary,thisstudypresentsanewtypeofdual-colornanobubblethatcanenhancethebiologicalluminescencesignalofinflammationtoimproveimagingsensitivity.Theresultssuggestthatthedual-colornanobubbleshavehighspecificityforinflammatorycells,lowtoxicity,andgoodbiocompatibility,indicatingagoodapplicationprospectforinflammation-relateddiseases.Thisnewtypeofdual-colornanobubbleoffersanewplatformforunderstandingthemechanismsofinflammationdevelopmentandimprovingtheaccuracyofdiseasediagnosis.Thedevelopmentofinflammationiscloselyassociatedwithmanydiseases,suchasrheumatoidarthritis,atherosclerosis,andcancer.Accurateimagingofinflammatorycellscanhelptodiagnosethesediseasesintheirearlystagesandmonitordiseaseprogression.However,traditionalimagingtechniqueshavelimitationsinsensitivityandspecificity.Therefore,thedevelopmentofnewandeffectiveimagingagentsforinflammationisofgreatsignificance.

Inrecentyears,nanobubbleshavebeenincreasinglyusedasimagingagentsduetotheiruniqueproperties,suchashighstabilityinblood,goodbiocompatibility,andtheabilitytoencapsulatevariousdrugsandimagingagents.However,thelowimagingsensitivityoftraditionalnanobubblesstillhinderstheirclinicalapplication.Tosolvethisproblem,researchershavebeenexploringnewtypesofnanobubblesthatcanenhanceimagingsensitivity.

Recently,ateamofresearchershasdevelopedanewtypeofdual-colornanobubblethatcanenhancethebiologicalluminescencesignalofinflammation.Thedual-colornanobubbleiscomposedofalipidshellandabioluminescentagent,whichcanemittwodifferentcolorsoflightunderdifferentconditions.Thelipidshellcanalsobefunctionalizedwithtargetingligands,suchasantibodiesorpeptides,tospecificallybindtoinflammatorycells.

Theresearcherstestedthedual-colornanobubbleinvitroandinvivoonananimalmodelofinflammation.Theyfoundthatthenanobubblescanspecificallylabelinflammatorycells,andthebioluminescencesignalissignificantlyenhancedcomparedtotraditionalimagingagents.Thenanobubblesalsoshowedlowtoxicityandgoodbiocompatibility,indicatingtheirpotentialforclinicaluse.

Overall,thedevelopmentofdual-colornanobubblesprovidesanewplatformforthestudyofinflammationandtheimprovementofdiseasediagnosis.Thehighspecificityandsensitivityofthenanobubblesoffergreatpotentialforearly-stagedetectionandmonitoringofinflammatorydiseases,whichcansignificantlyimprovetheirclinicalmanagementandoutcomes.Furthermore,thedual-colornanobubblescanalsobeutilizedforotherbiomedicalapplications.Forinstance,theycanbeloadedwithdrugsorgenesfortargeteddeliverytoinflamedtissues.Whenstimulatedwithultrasound,thenanobubblescanreleasethepayload,leadingtolocalizedtherapeuticeffectswhileminimizingsideeffectsinhealthytissues.Thisapproach,knownassonoporation,hasshownpromisingresultsinpreclinicalstudiesandiscurrentlybeingevaluatedinclinicaltrialsforvariousdiseases.

Inaddition,thedual-colornanobubblescanalsobeusedforimagingotherbiologicalprocesses,suchasangiogenesis,tumorgrowth,anddrugmetabolism.Byconjugatingspecifictargetingligandsorfluorescentdyestothenanobubbles,researcherscancreatecustomizedprobesforvariousbiologicaltargets.Moreover,theuseofadvancedimagingtechniques,suchasconfocalmicroscopy,multiphotonmicroscopy,andopticalcoherencetomography,canenhancethespatialresolutionanddepthpenetrationoftheimaging,enablingvisualizationofbiologicalstructuresandeventsatthecellularandsubcellularlevels.

Inconclusion,thedevelopmentofdual-colornanobubblesrepresentsasignificantadvancementinthefieldofbiomedicalimagingandtherapeutics.Theiruniqueopticalandacousticproperties,aswellastheirbiocompatibilityandlowtoxicity,makethemidealforstudyinganddiagnosingvariousinflammatorydiseases.Furthermore,theirpotentialfortargeteddrugorgenedeliveryandmultifunctionalimagingopensupnewopportunitiesforprecisionmedicineandpersonalizedhealthcare.Assuch,continuedresearchanddevelopmentofdual-colornanobubblesarewarranted,withthegoaloftranslatingthemintoclinicalpracticeforthebenefitofpatientsworldwide.Withtherapidadvancementsinnanotechnology,nanobubbleshaveemergedasanexcitingplatformforbiomedicalapplications.Dual-colornanobubbles,inparticular,havegarneredsignificantattentionduetotheiruniqueopticalpropertiesandpotentialfordiseasediagnosisandtherapy.

Onemajoradvantageofdual-colornanobubblesistheirabilitytofluoresceintwodistinctcolors.Thispropertycanbeexploitedfortargetedimagingofspecificcellsortissueswithhighspecificityandsensitivity.Forinstance,byfunctionalizingthenanobubbleswithbiomoleculesthatcanbindtospecificdiseasebiomarkers,dual-colornanobubblescanbeusedtodetectandmonitorvariousinflammatorydiseases,includingcancer,arthritis,andatherosclerosis.Additionally,thedifferentcolorscanhelpdistinguishbetweenhealthyanddiseasedcells,enablingnon-invasivemonitoringofdiseaseprogressionandtreatmentefficacy.

Anotheradvantageofdual-colornanobubblesistheirbiocompatibilityandlowtoxicity.Thesepropertiesmakethemsafeforuseinvivoandreducetheriskofadverseeffects.Furthermore,theirsmallsizeallowsthemtoeasilypenetratebiologicalbarriersandtargetspecificcellsortissues,reducingthedosesrequiredforeffectivetherapy.

Dual-colornanobubblescanalsoserveasapowerfultoolfortargeteddrugdelivery.Byencapsulatingdrugswithinthenanobubblesandfunctionalizingtheirsurfacewithspecifictargetingmoieties,drug-loadednanobubblescanselectivelybindtodiseasedcells,facilitatingthereleaseofthedrugatthesiteofaction.Thisapproachcanincreasetheefficacyofthedrugwhileminimizingoff-targeteffectsandreducingtherequireddose.

Lastly,themultifunctionalnatureofdual-colornanobubblesallowsthemtobeusedforawiderangeofbiomedicalapplicationsbeyonddiseasediagnosisandtherapy.Forinstance,theycanbeusedformolecularimaging,genedelivery,andtissueengineering,amongothers.

Inconclusion,dual-colornanobubblesareapromisingplatformforbiomedicalapplications.Theiruniqueopticalproperties,biocompatibility,andmultifunctionalitymakethemidealfordiseasediagnosisandtherapy,targeteddrugdelivery,andotherbiomedicalapplications.Continuedresearchanddevelopmentofthistechnologyareessentialtofullyrealizetheirpotentialandtranslatethemintoclinicalpracticeforthebenefitofpatientsworldwide.Furtherresearchanddevelopmentinthefieldofdual-colornanobubblescanhelpovercomecurrentchallengesandlimitations.Forinstance,effortscanbemadetooptimizethesynthesismethodsandparameterstoachievehigheryields,stability,anduniformityofthenanobubbles.Moreover,investigationsintothelong-termeffectsandbiodegradabilityoftheseparticlesinvivoarenecessarytoensuretheirsafetyandefficacyasclinicaltools.

Onepotentialapplicationofdual-colornanobubblesisincancertherapy.Forinstance,theseparticleshavebeenengineeredtocarryanticancerdrugsandselectivelydeliverthemtotumorcellsbyutilizingtheenhancedpermeabilityandretention(EPR)effect.Additionally,photothermaltherapycanbecombinedwithnanobubblestoincreasethetemperatureoftumorsandenhancedrugdeliveryefficiency.Furtherresearchinthisareacanleadtothedevelopmentofmoreeffectiveandtargetedcancertreatments.

Anotherareaofinterestfordual-colornanobubblesisinregenerativemedicine,particularlyintissueengineering.Nanobubblescanbeusedtomodulatetheactivityofstemcellsandpromotetissueregeneration.Bydeliveringgrowthfactorsandothertherapeuticmoleculestodamagedordiseasedtissues,nanobubblescanhelpimprovehealingandregeneration.

Insummary,dual-colornanobubblesareapromisingandversatiletoolinbiomedicalresearchandapplications.Theiruniquepropertiesmakethemusefulinavarietyoffields,includingcancertherapy,regenerativemedicine,andmolecularimaging.Continuedresearchanddevelopmentinthisfieldwillhelpoptimizetheirproperties,expandtheirapplications,andultimatelytranslatethemintoclinicalpractice.Inadditiontothecurrentapplicationsofdual-colornanobubbles,ongoingresearchisexploringtheirpotentialuseinotherareasofbiomedicine.Forexample,theabilityofthesenanobubblestoselectivelydeliverdrugstocancercellssuggeststheycouldbeusedasatargeteddrugdeliverysystem.Thiscouldminimizesideeffectsandmaximizetheefficacyofcancertreatments.

Furtherresearchisalsoexploringthepotentialfordual-colornanobubblesascontrastagentsinmedicalimaging.Theiruniqueopticalpropertiesallowforhigh-resolutionvisualizationofbiologicaltissuesandstructures,makingthemusefulinvariousimagingtechniquessuchasphotoacousticimaging,fluorescenceimaging,andopticalcoherencetomography.

Anotherpromisingapplicationofdual-colornanobubblesisintissueengineeringandregenerativemedicine.Byreleasinggrowthfactorsandpromotingcellularproliferation,thesenanobubblescanhelpstimulatetissuerepairandregeneration.Thiscouldbeparticularlyusefulintreatinginjuriesorconditionsthatresultintissuedamageorloss,suchasheartdisease,osteoarthritis,andnerveinjuries.

Overall,thedevelopmentanduseofdual-colornanobubblesisanexcitingandrapidlyevolvingfieldinbiomedicine.Withtheiruniquepropertiesandpotentialapplications,thesenanobubblescouldrevolutionizethewaywediagnoseandtreatdisease.Asfurtherresearchanddevelopmentareundertaken,wecanlookforwardtonewandinnovativeusesfortheseversatilenanoparticles.Inadditiontotheirpotentialusesinimagingandtherapeuticapplications,dual-colornanobubblesalsoholdpromiseindrugdelivery.Oneofthemajorchallengesindrugdeliveryisachievingtargeteddeliverytospecifictissuesandcellswhileminimizingoff-targeteffects.Dual-colornanobubblescouldpotentiallyovercomethischallengebyallowingforreal-timemonitoringofdrugdeliveryanddistribution.

Forexample,astudypublishedinACSAppliedMaterials&Interfacesdemonstratedtheuseofdual-colornanobubblesfortargeteddrugdeliveryincancercells.Theresearchersloadedthenanobubbleswithachemotherapydrugandafluorescentdye,whichallowedthemtovisualizeboththedrugandthenanobubblesinreal-time.Theythendeliveredthenanobubblestocancercellsandusedultrasoundtorupturethebubbles,releasingthedrugdirectlyintothecells.Thedual-colorimagingallowedtheresearcherstoconfirmthatthe