《Temperature-adaptive hydrogel optical waveguide with soft tissue-affinity for thermal regulated interventional photomedicine.docx》由会员分享，可在线阅读，更多相关《Temperature-adaptive hydrogel optical waveguide with soft tissue-affinity for thermal regulated interventional photomedicine.docx（11页珍藏版）》请在课桌文档上搜索。
1、naturecommunicationsArticlehttps:doi.org/10.1038/s41467-022-35440-wTemperature-adaptivehydrogelopticalwaveguidewithsofttissue-affinityforthermalregulatedinterventionalphotomedicineReceived: 21 January 2022Accepted: 2 December 2022Published online: 16 December 2022Check for updatesGuoyinCheni,KaiHouO
2、State Key Laboratory for Modifi cation of Chemical Fibers and Polymer Materials, College of Materials Science and Engineerinq, Donghua University, 2999 North Renmin Road, Shanghai 201620, China. iDepartment of Chemistry, Stony Brook University, Stony Brook, NewYork, NY 11794r USA.e-mail: houkai711;
3、rancao; zmf,NuoYui,PeilingWeii,TaoChem,CaihongZhangi,ShunWang,HongmeiLiu,RanCao1,LipingZhuBenjaminS.HsiaoS&MeifangZhuO1Photomedicinehasgainedgreatattentionduetoitsnontoxicity,goodselectivityandsmalltrauma.However,owingtothelimitedpenetrationoflightanddifficultmonitoringofthephoto-mediatherapies,itis
4、challengingtoapplyphotomedicaltreatmentindeeptissueastheymaydamagenormaltissues.Herein,athermalregulatedinterventionalphotomedidnebasedonatemperature-adaptivehydrogelIiber-basedopticalwaveguide(THFOW)isproposed,capableofeliminatingdeeplyseatedtumorcellswhileloweringrisksofovertemperature(causesthede
5、athofhealthycellsaroundthetumor).TheTHFOWisfabricatedbyanintegratedhomogeneous-dynamiccrosslinking-spinningmethod,andshowsaremarkablesofttissue-affinity(lowcytotoxicity,swellingstability,andsofttissue-likeYoung,smodulus).Moreover,theTHFOWshowsanexcellentlightpropagationpropertywithdifferentwavenumbe
6、rs(especially-0.32dBcm-with915nmlaserlight),andtemperature-gatedlightpropagationeffect.TheTHFOWandrelevanttherapeuticstrategyofferapromisingapplicationforintelligentphotomedicineindeepissue.Inrecentyears,asanemergingtechnology,photomedicinehasbeenusedfortreatingcancerousdiseaseswithadvantagesofsmall
7、trauma,nontoxicity,andgoodselectivity!Thetreatmentisprincipallybasedonthelight-inducedphysicalreactions(generationofheat,suchasphotothermaltherapy)-chemicalreaction(photochemicalreaction)?.,orbiologicalprocesses(optogenetic,PhOtObioIogiCaI)Gontothediseaselocationbyinducingexogenousphotosensitivereag
8、ent如.However,asthelightpenetratesonlyafewcentimetersthroughthetissue,itisdifficulttoapplyphotomedicaltreatmentindeeptissueu.Interventionaltherapyisoneofthemosteffectiveclinicaltreatmentstoreplacethedeeplyinvasivesurgicaloperations,whichreliesmainlyonanintervenedmedium(metalwire,silicaopticalfiber,et
9、c.)toimportapparatusintothedeeplyseateddiseaselocation.Andinvitroequipment(suchlikecomputedtomographyangiography,ultrasound,magneticresonance,andetc.)iscombinedtorealizediagnosisandtreatmenti4,s.Inconsequence,inthewaythatlightguidesusedforinterventionaltherapy,photomedicinecouldeffectivelysolvethepr
10、oblemoflightpenetrationthroughtissue.Althoughlight-guidessuchassilica-andpolymer-basedopticalfibershavebeenproventobefeasible,theirstiffnessandpoorbiocompatibilitymaycauseinflammationordamagetohosttissue12j6.Besides,duringphotomedicaltreatment,thephoto-inducedeffectsshouldbecontrolledinamannertoavoi
11、dthedamageofnormaltissuearoundthediseaseslocationTothisend,combiningequipmentassistedimagingtechniquewithinterventionalphotomedicaltreatmenttomonitorandguidethetherapeuticprocessisanefficientwayiu.However,thiskindoftreatmentishigh-cost,time-consumingandcomplicated.Hence,anef-fidentmethodfordynamican
12、dpreciseinsituphysiologicalmicroenvironmentalmonitoring(temperature,pH,etc.)isdesiredforguidingthephotomedicaltherapeuticprocessinacontrolledmannerunderthedeeptissue.Hydrogel-basedopticalWaveguideareidealcandidatesforusingasintervenedlight-guidesforaccurateandtargetedlightpropagationa.i9.Asamatrix,h
13、ydrogelscanbeextensivelymodifiedbymoleculardesignandrealizeenvironmentalresponses,suchastemperature,pH,andmolecularresponse”.；Inthisregard,fabricatinghydrogelopticalwaveguidewithacertaincondensedstructureandadjustableopticalproperties,couldrealizelightguidingandphysiologicalmicroenvironmentalmonitor
14、ingsimultaneously.Forexample,basedonthecoiltoglobulewinducedtransparency-opacitytransitionatthelowercriticalsolutiontemperature(LCST)1thermosensitivehydrogelscouldbeusedastemperature-dependentopticalswitches”.However,monomerswerenotpreferredforfiberformingduetoinsufficientinteraction.Furthermore,ine
15、vitablephaseseparationduringexothermicfreeradicalpolymerizationwouldinduceagglomerationofmolecularchainsorcross-linkedmicroregions,whicharedisadvantageousforfunctionalhydrogelfiberformation,thusitisdifficulttoobtainahydrogelfiberwithauniformstructure.Inthiswork,adesiredtemperature-adaptivehydrogelfi
16、ber-basedopticalwaveguide(THFOW)isfabricatedbyanintegratedhomogeneous-dynamic-crosslinking-spinningonlarge-scale.ThefabricatedTHFOWshowsanexcellentlightpropagationpropertywithdifferentwavenumbers(especially-0.32dBCm-oflightattenuationwith915nmlaserlight)andhighlysensitivetemperature-gatedlightpropag
17、ationeffect.Inaddition,athermalregulatedinterventionalphotomedicinebasedontheTHFOWisdemonstrated,capableofeliminatingdeeplyseatedtumorcellswhileloweringtherisksofovertemperature.Inconsequence,thefabricatedTHFOWshowsagreatpotentialforapplicationinthefieldofintelligentphotomedicine.Resultsanddiscussio
18、nConceptofthermalregulatedinterventionalphotomedicineAconceptofthermalregulatedinten/entionalphotomedicine(Fig.1)isproposedhere,whichiscapableofefficientlyeliminatingthetumorcellswhileloweringtherisksoftheovertemperaturethatcausesthedeathofnormalcellsaroundthetumorsite.Firstwithremarkablesofttissue-
19、affinity,thefabricatedTHFOWcanbeimplantedintodeeptissuesofhumanbodyandtargetthetumorsitewithoutinflanimation.TheuniformgelstructureandhightransparenceenabletheTHFOWefficientlytransport915nmlaserlightfromexternallaserequipmenttothediseasesiteinvivo.Consequently,photothermalheatingaroundthetumorisindu
20、cedaspre-injectedphotothermalnanoparticlesFig.1Aconceptofthermalregulatedinterventionalphotomedicine.Schematicillustrationofthethermalregulatedinterventionalphotomedicine(LCSTmeansthelowercriticalsolutiontemperature)indeeptissuebyusingthetemperature-adaptivehydrogeliberbasedopticalwaveguide(THFOW).e
21、xposingto915nmNIRlaser.WhenthetemperatureofthetumorsiteapproachesLCSToftheTHFOW,phaseseparationwouldoccurbetweenthepolymernetworkandH2Owithinthecorehydrogelfiber,causingareducedtransparencyofTHFOW(Fig.1top-rightpart),andthe915nmNIRlaserwouldscatterthesurroundingtissue.Hence,thetemperatureofthetumors
22、itecanberegulatedaroundthelowercriticalsolutiontemperature(LCST)oftheTHFOW.Atthistemperature,thecancercellswillbeefficientlykilled,whileavoidingseriousdamagetothesurroundingnormaltissuecausedbyovertemperature.Thus,thefabricatedTHFOWshowedgreatapplicationpotentialinthefieldofintelligentphotomedicine.
23、ContinuoussynthesisandstructuralcharacterizationoftheTHFOWThekeyofthethermalregulatedinterventionalphotomedicineindeeptissueisfabricatinganopticalhydrogelfiberwithlowlightattenuationandtunablethermosensitivity.Here,WechoseN-isopropylacrylamide(NIPAM)asthefunctionalmonomer,andN,N-dimethylacrylamide(D
24、MAAm)asthehydrophiliccomponenttotunetheLCSTofthefabricatedhydrogel.Toobtainalowlightguidingattenuation,theopticaltransparencyoftherawmaterialsisanimportantparameter,andthecoreshouldhavehigherrefractiveindexthantheSIieathNg.AlltheNIPAM/DMAAm(ND)hydrogelsintuitivelyshowedahightransparencyfromthephotog
25、raphsofthe(NxD100-)50hydrogels(SupplementaryFig.1a)landSupplementaryFig.1bshowsthetransmittanceandphotographsofthe(NXDlOo-X)50hydrogels.Allthehydrogelsshowedahightransmittance(90%)inthe460-920nmrange,indicatinghightransparency,andthusguaranteedlowlightattenuatio116,a.Inaddition,theLCSTofthedifferent
26、(NXDloO-X)50hydrogelswasinvestigatedtoselectasuitablemonomercompositionforthepre-gelsolution(SupplementaryFig.2);whenthetemperaturewashigherthantheLCSTfphase-separation-causedopacitywasobservedin(NDoo-)sohydrogels(SupplementaryFig,2c),whichshowedasensitivetemperature-controlledswitchforlighttransmit
27、tance.Furthermore,itcanbeseenthatwiththeincreaseinDMAAm,theLCSTofthefabricatedhydrogelincreased,andcoincidedwiththeformulaofLCST=31.37+0.58XCd,whereCdistheconcentrationofDMAAmintotalmonomers,causedbyincreaseinDMAAm(hydrophilicity)content.Asthehydrophiliccomponentinthepolymernetworkincreased,itrequir
28、esahighertemperaturetotriggerthephase-separatio2i.22.Consideringthesuitabilityoftransmittanceandthermosensitivity,and48wasthetemperaturethatcouldefficientlyeliminatethecancercells,thuswechose(N70D30)50(LCST=48.6)astheprecursorcompositiontofabricatethedesiredTHFOW.THFOWwasfabricatedusinganintegratedh
29、omogeneous-dynamic-crosslinking-spinningmethod.AsillustratedinFig.2a,2wt%Na-alginatesolutionand(N70D30)50solutionwereusedassheathandcorespinningsolution,respectively.Theformingprocessesmainlyconsistoftwostages:duringthefirststage,theNa-alginatesolutiongelledimmediatelyintotheCa-alginatesheathhydroge
30、lfiberwhenitwasinjectedintoaCaChcoagulatingbath(10C,asillustratedinthebottom-rightpartofFig.2a)?c”.Duringthesecondstage,thesheathhydrogeltubebringsthecoremonomersolutionintotheUVlightregion,whichtriggersradicalpolymerizationofdoublebondsamongthemonomers(NIPAm,DMAAm1andPEGDA),formingthecorehydrogelpo
31、lymernetworks(asillustratedinthetop-leftpartofFig.2a).However,owingtotheheatreleasedfromthepolymerization,thetemperaturewouldincreasesharplyovertheLCSTofthepre-gelledNIPAM-basedhydrogelwithouttimelyheatdissipation,causingphaseseparationwithinthethermosensitivepre-gelledcoremonomersolution.Thus,polym
32、erizationoccursintwodifferentphases,leadingtoinhomogeneouspolymernetworks.Toaddressthisproblem,thecoagulatingbathwascooledusingiceduringthespinningprocess(PAAmhydrogel力berwithfiberdiameterof500m(0.25dBcm-,with472nmlaserlight).ItcanbeseenthatTHFOWattenuation,asthelightwithalargerwavelengthhadbettertr
33、ansmissionthroughTHFOW(SupplementaryFig.1b).Furthermore,theresultsalsoshowthatdiameteroftheTHFOWsslightlyaffectthelightloss;thelargerthediameter,thesmallerthelightloss,whichwasduetothelongerraypropagationdistancesbeforereflectionatthesheath/coreinterfacewithinTHFOW-11.SupplementaryFig.8ashowslaserli
34、ghtwithdifferentpowercouldallpropagatethroughtheTHFOW,andthelightlossofthelightprofiIesshowsthatlightpowerdidntaffecttheattenuationofthelightinTHFOW(SupplementaryFig.8b).Inaddition,TheTHFOWcouldbeusedasanimplantablelight-guidetotransportNIRlight(SupplementaryFig.9),howeverispartiallydetectedbythedig
35、italcameraduetothattheNIRlightisakindofinvisiblelight.Thus,Wetestedthelightattenuationwiththe915nmNIRlightthroughtheTHFOWbythemethodofcutbacktechnique,theresultinFig.3dshowsthatthemeasuredlightlossoftheTHFOWsintheairwereintherangeof-0.32dBcm-：to0.39dBcm-.Temperature-gatedlightpropagationeffectThermo
36、sensitivityisakeypropertyoftheTHFOW1whichendowstheopticalhydrogelfiberwithintelligentresponsivenesstoenvironmentaltemperature,thusrealizingcontrollablephotothermalcancertherapyindeeptissue.AsshowninFig.4a,theTHFOWshowedexcellentlightpropagationwhenitwaspartlyimmersedinawaterUOnenUeAa M6-1 d (BP) coc
37、cser Length (cm)Fig. 3 Light propagation through the THFOW. a Laser light with different wavelength ( = 450, 515 and 650 nm) propagate through the THFOW; (b) Laser light propagates through THFOWs with different diameters; (c) Light attenuation of the THFOW calculated from the scattered light intensi
38、ty along with the THFOWprofi Ie (n = 3 independent experiments), data were presented as mean SD; (d) Propagation loss of the 915 nm laser light through THFOWs, measured by a cutback technique (n = 3 independent experiments), data were presented as mean SD. Scale bars in (a)r (b) are 1 cm.AirWater：Laser：LightV：LaserVLight4 2Fig. 4 Thermo-sensitivity of the THFOW. a Photos of light propagation through THFOW in water under different temperatures (48 C and 52 0C); (b) Photos of the light propagate through the THFOW with a segment of THFOW heating up and getting cool in sequence; (c) Light int
