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Lawula ukuhamba kwe-magnetic iron oxide nanoparticles ekunikezelweni okujoliswe kuyo kwe-cytostatics
Umbhali uToropova Y, Korolev D, Istomina M, Shulmeyster G, Petukhov A, Mishanin V, Gorshkov A, Podyacheva E, Gareev K, Bagrov A, Demidov O
Yana Toropova,1 Dmitry Korolev,1 Maria Istomina,1,2 Galina Shulmeyster,1 Alexey Petukhov,1,3 Vladimir Mishanin,1 Andrey Gorshkov,4 Ekaterina Podyacheva,1 Kamil Gareev,2 Alexei Bagrov,5 Oleg Demidov 6,71Almazov National Medical IZiko loPhando loMphathiswa wezeMpilo weRussian Federation, eSt. Petersburg, ngo-197341, iRussian Federation;I-2 St. Petersburg Electrotechnical University "LETI", iSt. Petersburg, i-197376, iRussian Federation;I-3 Centre for Personalized Medicine, i-Almazov State Medical Research Centre, iSebe lezeMpilo le-Russian Federation, iSt. Petersburg, i-197341, i-Russian Federation;I-4FSBI "I-Influenza Research Institute ebizwa ngokuba yi-AA Smorodintsev" iSebe lezeMpilo le-Russian Federation, eSt. Petersburg, eRussian Federation;5 Sechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Sciences, St. Petersburg, Russian Federation;6 RAS Institute of Cytology, St. Petersburg, 194064, Russian Federation;7INSERM U1231, iFaculty of Medicine kunye neKhemesti, Bourgogne-Franche Comté University of Dijon, France Unxibelelwano: Yana ToropovaAlmazov National Medical Research Centre, Ministry of Health of the Russian Federation, Saint-Petersburg, 197341, Russian Federation Tel +7 981 9526948006 [i-imeyile ekhuselweyo] Imvelaphi: Indlela ethembisayo kwingxaki ye-cytostatic toxicity kukusetyenziswa kwe-nanoparticles yamagnetic (MNP) yokuhanjiswa kweziyobisi ezijoliswe kuyo.Injongo: Ukusebenzisa izibalo ukufumanisa iimpawu ezintle zemagnethi ezilawula i-MNPs kwi-vivo, kunye nokuvavanya ukusebenza kakuhle kokuhanjiswa kwemagnetron ye-MNPs kwi-tumor ye-mouse in vitro kunye ne-vivo.(MNPs-ICG) isetyenziswa.Izifundo zobunzulu be-vivo luminescence zenziwa kwiimpuku zethumba, kunye nangaphandle kwemagnethi kwindawo yomdla.Ezi zifundo zenziwa kwi-scaffold ye-hydrodynamic ephuhliswe yi-Institute of Experimental Medicine ye-Almazov State Medical Research Centre yoMphathiswa wezeMpilo waseRashiya.Isiphumo: Ukusetyenziswa kwemagnethi ye-neodymium kukhuthaze ukuqokelelana okukhethiweyo kwe-MNP.Umzuzu omnye emva kokulawulwa kwe-MNPs-ICG kwiigundane ezithwala i-tumor, i-MNPs-ICG ikakhulu iqokelela esibindini.Ukungabikho kunye nobukho bomhlaba wamagnetic, oku kubonisa indlela yayo ye-metabolic.Nangona ukwanda kwe-fluorescence kwi-tumor kwabonwa phambi kommandla wamagnetic, ukuqina kwe-fluorescence kwisibindi sesilwanyana akuzange kutshintshe ngokuhamba kwexesha.Isiphelo: Olu hlobo lwe-MNP, oludityaniswe namandla ombane obalwayo, lunokuba sisiseko sophuhliso lonikezelo olulawulwa ngumagnetic lweziyobisi ze-cytostatic kwizicubu zethumba.Amagama angundoqo: uhlalutyo lwe-fluorescence, i-indocyanine, i-iron oxide nanoparticles, ukuhanjiswa kwe-magnetron ye-cytostatics, ukujoliswa kwethumba
Izifo zamathumba sesinye sezizathu eziphambili zokufa kwihlabathi liphela.Kwangaxeshanye, ukuguquguquka kokunyuka kokugula kunye nokufa kwezifo zamathumba kusekho.1 Ichemotherapy esetyenziswayo namhlanje iselolona nyango luphambili kumathumba ahlukeneyo.Kwangaxeshanye, uphuhliso lweendlela zokunciphisa ubutyhefu benkqubo ye-cytostatics lusabalulekile.Indlela ethembisayo yokusombulula ingxaki yetyhefu kukusebenzisa abathwali be-nano-scale ukujolisa kwiindlela zokuhanjiswa kweziyobisi, ezinokubonelela ngokuqokelelwa kwendawo yamachiza kwizicubu ze-tumor ngaphandle kokunyusa ukuqokelela kwazo kwizitho eziphilileyo kunye nezicubu.ugxininiso.2 Le ndlela yenza kube lula ukuphucula ukusebenza kunye nokujoliswa kweziyobisi ze-chemotherapeutic kwizicubu ze-tumor, ngelixa zinciphisa ubuthi benkqubo.
Phakathi kweentlobo ezahlukeneyo ze-nanoparticles ezicatshangelwayo ekunikezelweni okujoliswe kuyo kwe-cytostatic agents, i-nanoparticles yamagnetic (MNPs) inomdla okhethekileyo ngenxa yeekhemikhali zabo ezizodwa, i-biological, kunye ne-magnetic properties, eziqinisekisa ukuguquguquka kwazo.Ngoko ke, i-nanoparticles yamagnetic ingasetyenziselwa njengendlela yokufudumala ukunyanga izicubu nge-hyperthermia (magnetic hyperthermia).Zisenokusetyenziswa njengee-agent zokuxilonga (i-magnetic resonance diagnosis).I-3-5 Ukusebenzisa ezi mpawu, ezidityaniswe nokwenzeka kokuqokelela kwe-MNP kwindawo ethile, ngokusetyenziswa kwentsimi yamagnetic yangaphandle, ukuhanjiswa kwamalungiselelo amachiza ajoliswe kuyo kuvula ukudalwa kwenkqubo yemagnetron esebenzayo ukujolisa i-cytostatics kwindawo ye-tumor. Amathemba.Inkqubo enjalo iya kubandakanya i-MNP kunye nemimandla yamagnetic ukulawula ukuhamba kwabo emzimbeni.Kule meko, zombini imimandla yangaphandle yamagnetic kunye nokufakelwa kwemagnethi ebekwe kwindawo yomzimba equlethe i-tumor ingasetyenziswa njengomthombo wemagnethi.6 Indlela yokuqala ineentsilelo ezinzulu, kuquka imfuneko yokusebenzisa izixhobo ezikhethekileyo ukuze kujoliswe imagnethi yamachiza nemfuneko yokuqeqesha abasebenzi ukuze benze utyando.Ukongezelela, le ndlela inqunyelwe ngeendleko eziphezulu kwaye ifanelekile kuphela kwiithumba "ezingaphezulu" ezikufutshane nomzimba womzimba.Enye indlela yokusebenzisa ukufakelwa kwamagnetic yandisa ububanzi bokusetyenziswa kobu buchwepheshe, iququzelela ukusetyenziswa kwayo kumathumba abekwe kwiindawo ezahlukeneyo zomzimba.Zombini iimagnethi kunye neemagnethi ezidityaniswe kwi-stent ye-intraluminal zinokusetyenziswa njengokufakelwa komonakalo wethumba kumalungu angenanto ukuqinisekisa ilungelo lawo lodwa.Nangona kunjalo, ngokophando lwethu olungashicilelwanga, ezi zinto azikho ngokwaneleyo ukuze kuqinisekiswe ukugcinwa kwe-MNP kwigazi.
Ukusebenza kokunikezelwa kweziyobisi zemagneti kuxhomekeke kwizinto ezininzi: iimpawu zomthuthi kazibuthe ngokwawo, kunye neempawu zomthombo wemagnethi (kubandakanywa iiparamitha zejometri zemagnethi ezisisigxina kunye namandla ombane azivelisayo).Uphuhliso lwetekhnoloji yokuhanjiswa kwe-cell inhibitor ye-magnetic ekhokelwayo kufuneka ibandakanye uphuhliso lwezixhobo ezifanelekileyo zemagnethi ze-nanoscale drug carriers, ukuvavanya ukhuseleko lwabo, kunye nokuphuhlisa iprotocol yokubonwa evumela ukulandelela iintshukumo zabo emzimbeni.
Kolu phononongo, ngokwemathematika sibale ezona mpawu zintle zemagneti ukulawula umthwali weziyobisi wamagnetic nano-scale emzimbeni.Ukuba nokwenzeka kokugcina i-MNP ngodonga lwemithambo yegazi phantsi kwempembelelo yemagnethi esetyenziswayo enezi mpawu zokubala nayo yaphononongwa kwimithambo yegazi yeempuku eyodwa.Ukongeza, siye sadibanisa ii-conjugates ze-MNP kunye nee-agent ze-fluorescent kwaye saphuhlisa iprotocol yokubonwa kwazo kwi-vivo.Ngaphantsi kweemeko ze-vivo, kwiigundane ze-tumor model, ukuqokelela ukusebenza kakuhle kwe-MNPs kwi-tumor tissues xa ilawulwa ngenkqubo phantsi kwempembelelo yemagnethi yafundwa.
Kwisifundo se-in vitro, sasebenzisa i-MNP yereferensi, kwaye kwi-vivo study, sasebenzisa i-MNP ehlanganiswe ne-lactic acid polyester (i-polylactic acid, i-PLA) equkethe i-agent fluorescent (indolecyanine; ICG).I-MNP-ICG ifakiwe Kwimeko, sebenzisa (MNP-PLA-EDA-ICG).
I-synthesis kunye nezakhiwo kunye neekhemikhali ze-MNP zichazwe ngokweenkcukacha kwenye indawo.7,8
Ukuze kuhlanganiswe i-MNPs-ICG, i-PLA-ICG conjugates yaveliswa kuqala.Umxube we-powder racemic we-PLA-D kunye ne-PLA-L ene-molecular weight 60 kDa isetyenziswe.
Ekubeni i-PLA kunye ne-ICG zombini ii-acids, ukwenzela ukudibanisa i-PLA-ICG i-conjugates, okokuqala kufuneka udibanise i-amino-terinated spacer kwi-PLA, enceda i-ICG chemisorb kwi-spacer.I-spacer yenziwe kusetyenziswa i-ethylene diamine (EDA), indlela ye-carbodiimide kunye ne-carbodiimide e-soluble yamanzi, i-1-ethyl-3- (3-dimethylaminopropyl) i-carbodiimide (EDAC).I-PLA-EDA spacer yenziwe ngolu hlobo lulandelayo.Yongeza i-20-fold molar excess of EDA kunye ne-20-fold molar excess of EDAC ukuya kwi-2 mL ye-0.1 g / mL ye-PLA chloroform isisombululo.I-synthesis iqhutywe kwi-tube ye-polypropylene ye-15 mL kwi-shaker kwisantya se-300 min-1 kwiiyure ze-2.Iskimu sokudibanisa siboniswe kuMfanekiso 1. Phinda udibanise ngokuphindaphindiweyo kwe-200 ye-reagents yokwandisa i-synthesis scheme.
Ekupheleni kwe-synthesis, isisombululo sasiyi-centrifuged ngesantya se-3000 min-1 imizuzu ye-5 ukususa i-polyethylene derivatives engaphezulu kwe-precipitated.Emva koko, i-2 mL ye-0.5 mg / mL isisombululo se-ICG kwi-dimethyl sulfoxide (DMSO) yongezwa kwisisombululo se-2 mL.I-agitator igxininiswe kwisantya esishukumisayo se-300 min-1 kwiiyure ze-2.Umzobo oqingqiweyo we-conjugate efunyenweyo uboniswe kuMfanekiso 2.
Kwi-200 mg MNP, songeze i-4 mL ye-PLA-EDA-ICG conjugate.Sebenzisa i-LS-220 shaker (LOIP, eRashiya) ukuvuselela ukumiswa kwemizuzu engama-30 kwi-frequency ye-300 min-1.Emva koko, ihlanjwe nge-isopropanol kathathu kwaye ixhomekeke kukwahlukana kwamagnetic.Sebenzisa i-UZD-2 Ultrasonic Disperser (FSUE NII TVCH, eRashiya) ukongeza i-IPA ekumisweni kwemizuzu emi-5-10 phantsi kwesenzo esiqhubekayo se-ultrasonic.Emva kokuhlamba kwe-IPA yesithathu, i-precipitate ihlanjwe ngamanzi adibeneyo kwaye iphinde imiswe kwi-saline ye-physiological kwi-concentration ye-2 mg / mL.
Izixhobo ze-ZetaSizer Ultra (i-Malvern Instruments, e-UK) zisetyenziselwa ukufunda ukusabalalisa ubungakanani be-MNP efunyenwe kwisisombululo samanzi.I-microscope yokudluliselwa kwe-electron (TEM) kunye ne-JEM-1400 STEM emission field emission cathode (JEOL, Japan) yayisetyenziselwa ukufunda imilo kunye nobukhulu be-MNP.
Kwesi sifundo, sisebenzisa imagnethi esisigxina (inqanaba le-N35; kunye ne-nickel yokukhusela i-coating) kunye nobukhulu obulandelayo obuqhelekileyo (ubude be-axis ubude × ububanzi be-cylinder): 0.5 × 2 mm, 2 × 2 mm, 3 × 2 mm kunye ne-5 × 2 mm.
Uphononongo lwe-in vitro lwezothutho lwe-MNP kwinkqubo yomzekelo lwenziwa kwi-scaffold ye-hydrodynamic ephuhliswe yi-Institute of Experimental Medicine ye-Almazov State Medical Research Centre yeSebe lezeMpilo laseRashiya.Umthamo we-liquid ejikelezayo (amanzi adibeneyo okanye isisombululo se-Krebs-Henseleit) yi-225 mL.Imagnethi ye-Axially cylindrical magnetic isetyenziswa njengemagnethi esisigxina.Beka imagnethi kwisibambi se-1.5 mm kude nodonga lwangaphakathi lombhobho weglasi ephakathi, kunye nesiphelo sayo sijonge kwicala letyhubhu (ethe nkqo).Isantya sokuhamba kwamanzi kwi-loop evaliweyo yi-60 L / h (ehambelana nesantya somgca we-0.225 m / s).Isisombululo se-Krebs-Henseleit sisetyenziselwa umbane ojikelezayo ngenxa yokuba i-analog ye-plasma.I-coefficient ye-viscosity eguqukayo ye-plasma yi-1.1-1.3 mPa∙s.9 Ubungakanani be-MNP efakwe kwi-adsorbed kumhlaba wemagnethi imiselwa yi-spectrophotometry ukusuka kuxinzelelo lwentsimbi kulwelo olujikelezayo emva kovavanyo.
Ukongeza, uphononongo lovavanyo luye lwenziwa kwitheyibhile ephuculweyo ye-fluid mechanics ukumisela ukunyanzeliswa kwemithambo yegazi.Amacandelo aphambili enkxaso ye-hydrodynamic aboniswe kuMfanekiso 3. Amacandelo aphambili e-hydrodynamic stent yi-loop evaliweyo eyenza i-cross-section ye-system vascular system kunye ne-tank yokugcina.Ukuhamba kwemodeli ye-fluid kunye ne-contour yemodyuli yesitya segazi kubonelelwa ngepompo ye-peristaltic.Ngexesha lovavanyo, gcina i-vaporization kunye noluhlu olufunekayo lobushushu, kwaye ubeke iliso kwiiparamitha zenkqubo (ubushushu, uxinzelelo, izinga lokuhamba kwamanzi, kunye nexabiso le-pH).
Umzobo 3 Umzobo webhlokhi yokuseta esetyenziselwa ukufunda ukunyanzeliswa kodonga lomthambo we-carotid.Itanki yokugcina i-1, impompo ye-peristaltic ye-2, i-3-inkqubo yokwazisa ukumiswa okuqulethe i-MNP kwi-loop, i-4-flow meter, i-sensor ye-5-pressure kwi-loop, i-6-heat exchanger, i-7-chamber ene-container, i-8-umthombo yommandla wemagnethi, 9-ibhaluni enehydrocarbons.
Igumbi eliqulathe isikhongozeli liqulathe izikhongozeli ezintathu: isitya esikhulu sangaphandle kunye nezikhongozeli ezibini ezincinci, apho iingalo zesekethe esembindini zidlula khona.I-cannula ifakwe kwi-container encinci, i-container ifakwe kwi-container encinci, kwaye incam ye-cannula iboshwe ngokuqinileyo ngocingo oluncinci.Isithuba phakathi kwesitya esikhulu kunye nesitya esincinci sizaliswe ngamanzi adibeneyo, kwaye ubushushu buhlala buhlala buhlala buhlala ngenxa yokudibanisa kwi-heat exchanger.Isithuba kwisitya esincinci sigcwele isisombululo se-Krebs-Henseleit ukugcina ukusebenza kweeseli zemithambo yegazi.Itanki iphinde izaliswe isisombululo se-Krebs-Henseleit.Inkqubo yokubonelela ngegesi (ikhabhoni) isetyenziselwa ukukhupha isisombululo kwisitya esincinci kwitanki yokugcina kunye negumbi eliqulethe isitya (Umfanekiso 4).
Umfanekiso wesi-4 Igumbi apho isitya sibekwe khona.I-1-Cannula yokunciphisa imithwalo yegazi, i-2-Igumbi langaphandle, i-3-Igumbi elincinci.Utolo lubonisa icala lemodeli yolwelo.
Ukumisela isalathiso esihambelanayo sokungena kwindonga yomkhumbi, i-rat carotid artery isetyenzisiwe.
Ukuqaliswa kokumiswa kwe-MNP (0.5mL) kwinkqubo inezi mpawu zilandelayo: umthamo wangaphakathi wetanki kunye nokudibanisa umbhobho kwi-loop yi-20mL, kwaye umthamo wangaphakathi wegumbi ngalinye ngu-120mL.Umthombo wangaphandle wemagnethi ngumagnethi osisigxina kunye nobukhulu obuqhelekileyo be-2 × 3 mm.Ifakwe ngaphezu kwelinye lamagumbi amancinci, i-1 cm ukusuka kwisitya, kunye nesiphelo esinye sijonge eludongeni lwesikhongozeli.Ubushushu bugcinwa kuma-37°C.Amandla ompompo we-roller abekwe kwi-50%, ehambelana nesantya se-17 cm / s.Njengolawulo, iisampulu zathathwa kwiseli ngaphandle kweemagnethi ezisisigxina.
Iyure enye emva kokulawulwa koxinzelelo olunikiweyo lwe-MNP, isampuli yolwelo yathathwa kwigumbi.I-particle concentration yalinganiswa nge-spectrophotometer usebenzisa i-Unico 2802S UV-Vis i-spectrophotometer (i-United Products & Instruments, e-USA).Ukuthathela ingqalelo i-spectrum ye-absorption yokumiswa kwe-MNP, umlinganiselo wenziwa kwi-450 nm.
Ngokwemigaqo ye-Rus-LASA-FELASA, zonke izilwanyana ziphakanyiswe kwaye zikhuliswe kwiindawo ezithile ezingenayo i-pathogen.Olu phononongo luhambelana nayo yonke imimiselo yokuziphatha efanelekileyo yovavanyo lwezilwanyana kunye nophando, kwaye ifumene imvume yokuziphatha kwi-Almazov National Medical Research Centre (IACUC).Izilwanyana zazisela amanzi ad libitum kwaye zondla rhoqo.
Uphononongo lwenziwe kwi-10 ene-anesthetized ye-12-iveki-ubudala eyindoda ye-NSG yeempuku (NOD.Cg-Prkdcscid Il2rgtm1Wjl/Szj, Jackson Laboratory, USA) 10, enobunzima be-22 g ± 10%.Ekubeni i-immunity ye-immunodeficiency mice igxininiswe, iigundane ze-immunodeficiency zalo mgca zivumela ukutshintshwa kweeseli zomntu kunye nezicubu ngaphandle kokulahlwa kokutshintshwa.Ii-littermates ezivela kwiikheji ezahlukeneyo zabelwa ngokungenamkhethe kwiqela lokulinga, kwaye zaye zadityaniswa okanye zavezwa ngokucwangcisiweyo kwindawo yokulala yamanye amaqela ukuze kuqinisekiswe ukuvezwa okulinganayo kwi-microbiota eqhelekileyo.
Umgca weseli yomhlaza womntu we-HeLa usetyenziselwa ukuseka imodeli ye-xenograft.Iiseli zaye zakhuliswa kwi-DMEM equkethe i-glutamine (i-PanEco, iRashiya), yongezwa nge-10% ye-fetal bovine serum (Hyclone, USA), i-100 CFU / mL penicillin, kunye ne-100 μg / mL streptomycin.I-cell line yanikezelwa ngobubele yiGene Expression Regulation Laboratory yeZiko loPhando lweCell yeRussia Academy of Sciences.Ngaphambi kokutofa, iiseli ze-HeLa zasuswa kwiplastiki yenkcubeko kunye ne-trypsin ye-1: 1: isisombululo se-Versene (i-Biolot, eRashiya).Emva kokuhlanjwa, iiseli zaye zaxhonywa kwindawo epheleleyo ukuya kugxininiso lweeseli ze-5 × 106 nge-200 μL, kwaye zixutywe nge-basement membrane matrix (i-LDEV-FREE, MATRIGEL® CORNING®) (1: 1, emkhenkceni).Ukunqunyanyiswa kweseli elungisiweyo kwafakwa ngaphantsi kwesikhumba kwithanga lempuku.Sebenzisa iicalipers zombane ukujonga ukukhula kwethumba rhoqo ngeentsuku ezi-3.
Xa i-tumor ifikelele kwi-500 mm3, imagnethi esisigxina yafakwa kwizicubu zomzimba zesilwanyana sokulinga kufuphi nethumba.Kwiqela lokulinga (MNPs-ICG + tumor-M), i-0.1 mL yokumiswa kwe-MNP yafakwa kwaye yavezwa kwintsimi yamagnetic.Izilwanyana ezinganyangwanga zisetyenziswe njengolawulo (imvelaphi).Ukongezelela, izilwanyana ezifakwe kwi-0.1 mL ye-MNP kodwa zingafakwanga ngamagnethi (MNPs-ICG + tumor-BM) zisetyenzisiwe.
Umboniso we-fluorescence we-vivo kunye neesampuli ze-vitro zenziwa kwi-IVIS Lumina LT series III bioimager (PerkinElmer Inc., USA).Ukuboniswa kwe-in vitro, umthamo we-1 mL ye-synthetic PLA-EDA-ICG kunye ne-MNP-PLA-EDA-ICG conjugate yongezwa kwimibhobho yeplate.Ukuthathela ingqalelo iimpawu ze-fluorescence zedayi ye-ICG, isihluzo esona sisetyenzisiweyo ukumisela ubukhulu obukhanyayo besampulu sikhethiwe: ubuninzi be-excitation wavelength yi-745 nm, kunye ne-emission wavelength yi-815 nm.I-software ye-Living Image 4.5.5 (i-PerkinElmer Inc.) isetyenziselwe ukulinganisa ngokobungakanani ubunzulu be-fluorescence yamaqula aqulathe i-conjugate.
Ubunzulu be-fluorescence kunye nokuqokelela kwe-conjugate ye-MNP-PLA-EDA-ICG balinganiswe kwi-vivo tumor model iigundane, ngaphandle kobukho kunye nokusetyenziswa kwendawo yamagnetic kwindawo yomdla.Iimpuku zaye zafakwa i-anesthetized nge-isoflurane, kwaye emva koko i-0.1 mL ye-conjugate ye-MNP-PLA-EDA-ICG yafakwa nge-vein yomsila.Iigundane ezingaphathwanga zisetyenziswe njengolawulo olubi ukufumana imvelaphi ye-fluorescent.Emva kokulawula i-conjugate nge-intravenously, faka isilwanyana kwindawo yokufudumala (37 ° C) kwigumbi le-IVIS Lumina LT series III fluorescence imager (PerkinElmer Inc.) ngelixa ugcina i-inhalation kunye ne-2% isoflurane anaesthetization.Sebenzisa i-ICG's eyakhelwe-ngaphakathi yokucoca (745-815 nm) ukuze ufumane uphawu lwe-1 iminithi kunye nemizuzu eyi-15 emva kokuqaliswa kwe-MNP.
Ukuvavanya ukuqokelelwa kwe-conjugate kwi-tumor, indawo ye-peritoneal yesilwanyana yayigqunywe ngephepha, okwenza kube lula ukuphelisa i-fluorescence eqaqambileyo ehambelana nokuqokelelwa kwamasuntswana esibindi.Emva kokufunda i-biodistribution ye-MNP-PLA-EDA-ICG, izilwanyana zanyanzeliswa ngobuntu ngokugqithiswa kwe-isoflurane anesthesia ukwenzela ukuhlukana okulandelayo kweendawo ze-tumor kunye novavanyo lobungakanani bemitha ye-fluorescence.Sebenzisa i-Living Image 4.5.5 software (PerkinElmer Inc.) ukwenza ngesandla uhlalutyo lwesignali ukusuka kummandla okhethiweyo onomdla.Imilinganiselo emithathu yathathwa kwisilwanyana ngasinye (n = 9).
Kolu phononongo, asikhange silinganise ukulayishwa ngempumelelo kwe-ICG kwi-MNPs-ICG.Ukongezelela, asizange siqhathanise ukusebenza kakuhle kokugcinwa kwe-nanoparticles phantsi kweempembelelo zamagnetic ezisisigxina zeemilo ezahlukeneyo.Ukongezelela, asizange sivavanye umphumo wexesha elide lentsimi yamagnetic ekugcinweni kwe-nanoparticles kwizicubu ze-tumor.
I-Nanoparticles ilawula, kunye nobukhulu obuphakathi kwe-195.4 nm.Ukongeza, ukunqunyanyiswa kuqulethe ii-agglomerates ezinobungakanani obuphakathi kwe-1176.0 nm (Umfanekiso 5A).Emva koko, inxalenye yahluzwa ngesihluzo se-centrifugal.Ikhono le-zeta leengqungquthela yi-15.69 mV (Umfanekiso 5B).
Umzobo 5 Iimpawu ezibonakalayo zokunqunyanyiswa: (A) ukusabalalisa ubungakanani besuntswana;(B) ukuhanjiswa kwamasuntswana kumandla e-zeta;(C) Ifoto ye-TEM ye-nanoparticles.
Ubungakanani be-particle ngokuyisiseko yi-200 nm (Umfanekiso 5C), owenziwe nge-MNP enye kunye nobukhulu be-20 nm, kunye ne-PLA-EDA-ICG igobolondo ye-organic conjugated ene-electron density ephantsi.Ukwenziwa kwee-agglomerate kwizisombululo ezinamanzi kunokuchazwa yimodyuli ephantsi ngokwentelekiso ye-electromotive force ye-nanoparticles nganye.
Kwimagnethi esisigxina, xa i-magnetization igxininiswe kumthamo we-V, intetho edibeneyo yahlulahlulwe yaba ziindibaniselwano ezimbini, ezizezi umthamo kunye nomphezulu:
Kwimeko yesampulu ene-magnetization eqhubekayo, ukuxinana kwangoku ngu-zero.Emva koko, intetho ye-vector induction magnetic iya kuthatha le fomu ilandelayo:
Sebenzisa inkqubo yeMATLAB (MathWorks, Inc., USA) ukubala amanani, inombolo yelayisensi ye-ETU "LETI" yezemfundo 40502181.
Njengoko kubonisiwe kwi-Figure 7 Umfanekiso we-8 Umzobo we-9 Umzobo-10, indawo enamandla kakhulu yamagnetic yenziwa yimagnethi ejoliswe kwi-axially ekupheleni kwe-cylinder.Iradiyasi esebenzayo yesenzo ilingana nejometri yemagnethi.Kwimagnethi ye-cylindrical ene-cylinder ubude bayo bukhulu kunobubanzi bayo, intsimi yamagnetic enamandla ibonwa kwi-axial-radial direction (kwicandelo elihambelanayo);ngoko ke, iisilinda ezinomlinganiselo omkhulu (ububanzi kunye nobude) i-adsorption ye-MNP yeyona isebenzayo.
Umzobo 7 Icandelo le-magnetic induction intensity Bz ecaleni kwe-Oz axis yemagnethi;ubungakanani obuqhelekileyo bemagnethi: umgca omnyama 0.5 × 2mm, umgca ohlaza okwesibhakabhaka 2 × 2mm, umgca oluhlaza 3 × 2mm, umgca obomvu 5 × 2mm.
Umzobo 8 Icandelo le-magnetic induction i-Br i-perpendicular kwi-axis yemagnethi ye-Oz;ubungakanani obuqhelekileyo bemagnethi: umgca omnyama 0.5 × 2mm, umgca ohlaza okwesibhakabhaka 2 × 2mm, umgca oluhlaza 3 × 2mm, umgca obomvu 5 × 2mm.
Umzobo 9 I-magnetic induction intensity Bz icandelo kumgama r ukusuka kwi-axis yokugqibela yemagnethi (z=0);ubungakanani obuqhelekileyo bemagnethi: umgca omnyama 0.5 × 2mm, umgca ohlaza okwesibhakabhaka 2 × 2mm, umgca oluhlaza 3 × 2mm, umgca obomvu 5 × 2mm.
Umzobo we-10 icandelo le-Magnetic induction ecaleni kwendlela ye-radial;ubungakanani umazibuthe umgangatho: umgca omnyama 0.5 × 2mm, umgca blue 2 × 2mm, umgca oluhlaza 3 × 2mm, umgca obomvu 5 × 2mm.
Iimodeli ezikhethekileyo ze-hydrodynamic zingasetyenziselwa ukufunda indlela yokuhanjiswa kwe-MNP kwizicubu ze-tumor, zigxininise i-nanoparticles kwindawo ekujoliswe kuyo, kwaye zinqume ukuziphatha kwee-nanoparticles phantsi kweemeko ze-hydrodynamic kwinkqubo yokujikeleza.Iimagnethi ezisisigxina zinokusetyenziswa njengemagnethi yangaphandle.Ukuba asiyikuhoxisa ukusebenzisana kwe-magnetostatic phakathi kwe-nanoparticles kwaye singacingi imodeli yamagnetic fluid, kwanele ukuqikelela ukusebenzisana phakathi kwemagnethi kunye ne-nanoparticle enye kunye ne-dipole-dipole approximation.
Apho u-m ngumzuzu wemagnethi wemagnethi, r yi-radius vector yendawo apho i-nanoparticle ikhoyo, kwaye u-k ngumba wenkqubo.Kuqikelelo lwe-dipole, intsimi yemagnethi inesimo esifanayo (Umfanekiso 11).
Kwindawo efanayo yamagnetic, i-nanoparticles ijikeleza kuphela kwimigca yamandla.Kwindawo yemagnethi engafaniyo, amandla asebenza kuwo:
Iphi i-derivative yesalathiso esinikiweyo l.Ukongezelela, amandla adonsa i-nanoparticles kwiindawo ezingalinganiyo zentsimi, oko kukuthi, i-curvature kunye nobuninzi bemigca yokunyuka kwamandla.
Ke ngoko, kuyinqweneleka ukusebenzisa imagnethi eyomeleleyo ngokwaneleyo (okanye ikhonkco lemagnethi) kunye ne-axial anisotropy ebonakalayo kwindawo apho amasuntswana akhoyo.
Itheyibhile ye-1 ibonisa amandla ombane omnye njengomthombo owaneleyo wemagnethi ukubamba kunye nokugcina i-MNP kwibhedi ye-vascular of the field application.