Temperature-adaptive hydrogel optical waveguide with soft tissue-affinity for thermal regulated interventional photomedicine.docx

naturecommunicationsArticlehttps:doi.org/10.1038/s41467-022-35440-wTemperature-adaptivehydrogelopticalwaveguidewithsofttissue-affinityforthermalregulatedinterventionalphotomedicineReceived: 21 January 2022Accepted: 2 December 2022Published online: 16 December 2022Check for updatesGuoyinCheni,KaiHouOState 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; rancao; zmf,NuoYui,PeilingWeii,TaoChem,CaihongZhangi,ShunWang,HongmeiLiu,RanCao1,LipingZhuBenjaminS.HsiaoS&MeifangZhuO1Photomedicinehasgainedgreatattentionduetoitsnontoxicity,goodselectivityandsmalltrauma.However,owingtothelimitedpenetrationoflightanddifficultmonitoringofthephoto-mediatherapies,itischallengingtoapplyphotomedicaltreatmentindeeptissueastheymaydamagenormaltissues.Herein,athermalregulatedinterventionalphotomedidnebasedonatemperature-adaptivehydrogelIiber-basedopticalwaveguide(THFOW)isproposed,capableofeliminatingdeeplyseatedtumorcellswhileloweringrisksofovertemperature(causesthedeathofhealthycellsaroundthetumor).TheTHFOWisfabricatedbyanintegratedhomogeneous-dynamiccrosslinking-spinningmethod,andshowsaremarkablesofttissue-affinity(lowcytotoxicity,swellingstability,andsofttissue-likeYoung,smodulus).Moreover,theTHFOWshowsanexcellentlightpropagationpropertywithdifferentwavenumbers(especially-0.32dBcm-with915nmlaserlight),andtemperature-gatedlightpropagationeffect.TheTHFOWandrelevanttherapeuticstrategyofferapromisingapplicationforintelligentphotomedicineindeepissue.Inrecentyears,asanemergingtechnology,photomedicinehasbeenusedfortreatingcancerousdiseaseswithadvantagesofsmalltrauma,nontoxicity,andgoodselectivity!Thetreatmentisprincipallybasedonthelight-inducedphysicalreactions(generationofheat,suchasphotothermaltherapy)-chemicalreaction(photochemicalreaction)?.,orbiologicalprocesses(optogenetic,PhOtObioIogiCaI)Gontothediseaselocationbyinducingexogenousphotosensitivereagent如.However,asthelightpenetratesonlyafewcentimetersthroughthetissue,itisdifficulttoapplyphotomedicaltreatmentindeeptissue®u.Interventionaltherapyisoneofthemosteffectiveclinicaltreatmentstoreplacethedeeplyinvasivesurgicaloperations,whichreliesmainlyonanintervenedmedium(metalwire,silicaopticalfiber,etc.)toimportapparatusintothedeeplyseateddiseaselocation.Andinvitroequipment(suchlikecomputedtomographyangiography,ultrasound,magneticresonance,andetc.)iscombinedtorealizediagnosisandtreatmenti4,s.Inconsequence,inthewaythatlightguidesusedforinterventionaltherapy,photomedicinecouldeffectivelysolvetheproblemoflightpenetrationthroughtissue.Althoughlight-guidessuchassilica-andpolymer-basedopticalfibershavebeenproventobefeasible,theirstiffnessandpoorbiocompatibilitymaycauseinflammationordamagetohosttissue12j6.Besides,duringphotomedicaltreatment,thephoto-inducedeffectsshouldbecontrolledinamannertoavoidthedamageofnormaltissuearoundthediseaseslocationTothisend,combiningequipmentassistedimagingtechniquewithinterventionalphotomedicaltreatmenttomonitorandguidethetherapeuticprocessisanefficientwayiu.However,thiskindoftreatmentishigh-cost,time-consumingandcomplicated.Hence,anef-fidentmethodfordynamicandpreciseinsituphysiologicalmicroenvironmentalmonitoring(temperature,pH,etc.)isdesiredforguidingthephotomedicaltherapeuticprocessinacontrolledmannerunderthedeeptissue.Hydrogel-basedopticalWaveguideareidealcandidatesforusingasintervenedlight-guidesforaccurateandtargetedlightpropagationa.i9.Asamatrix,hydrogelscanbeextensivelymodifiedbymoleculardesignandrealizeenvironmentalresponses,suchastemperature,pH,andmolecularresponse”.；Inthisregard,fabricatinghydrogelopticalwaveguidewithacertaincondensedstructureandadjustableopticalproperties,couldrealizelightguidingandphysiologicalmicroenvironmentalmonitoringsimultaneously.Forexample,basedonthe"coiltoglobulewinducedtransparency-opacitytransitionatthelowercriticalsolutiontemperature(LCST)1thermosensitivehydrogelscouldbeusedastemperature-dependentopticalswitches”.However,monomerswerenotpreferredforfiberformingduetoinsufficientinteraction.Furthermore,inevitablephaseseparationduringexothermicfreeradicalpolymerizationwouldinduceagglomerationofmolecularchainsorcross-linkedmicroregions,whicharedisadvantageousforfunctionalhydrogelfiberformation,thusitisdifficulttoobtainahydrogelfiberwithauniformstructure.Inthiswork,adesiredtemperature-adaptivehydrogelfiber-basedopticalwaveguide(THFOW)isfabricatedbyanintegratedhomogeneous-dynamic-crosslinking-spinningonlarge-scale.ThefabricatedTHFOWshowsanexcellentlightpropagationpropertywithdifferentwavenumbers(especially-0.32dBCm-oflightattenuationwith915nmlaserlight)andhighlysensitivetemperature-gatedlightpropagationeffect.Inaddition,athermalregulatedinterventionalphotomedicinebasedontheTHFOWisdemonstrated,capableof