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Lawula intshukumo yee-nanoparticles ze-magnetic iron oxide ukuze kuhanjiswe i-cytostatics ekujoliswe kuyo
Umbhali uToropova Y, Korolev D, Istomina M, Shulmeyster G, Petukhov A, Mishanin V, Gorshkov A, Podyacheva E, Gareev K, Bagrov A, Demidov O
UYana Toropova,1 uDmitry Korolev,1 uMaria Istomina,1,2 uGalina Shulmeyster,1 uAlexey Petukhov,1,3 uVladimir Mishanin,1 uAndrey Gorshkov,4 uEkaterina Podyacheva,1 uKamil Gareev,2 uAlexei Bagrov,5 uOleg Demidov6,71 iAlmazov National Medical Research Center of the Ministry of Health of the Russian Federation, eSt. Petersburg, 197341, kwiRussian Federation; 2 iSt. Petersburg Electrotechnical University “LETI”, eSt. Petersburg, 197376, kwiRussian Federation; 3 iZiko lezonyango ezizimeleyo, iAlmazov State Medical Research Center, kwiRussian Federation, eSt. Petersburg, 197341, kwiRussian Federation; 4FSBI “Influenza Research Institute ebizwa ngegama le-AA Smorodintsev” kwiRussian Federation, eSt. Petersburg, kwiRussian Federation; 5 iSechenov Institute of Evolutionary Physiology and Biochemistry, kwiRussian Academy of Sciences, eSt. Petersburg, kwiRussian Federation; 6 I-RAS Institute of Cytology, eSt. Petersburg, 194064, kwiRussian Federation; 7INSERM U1231, kwiFakhalthi yezonyango kunye neKhemesti, kwiYunivesithi yaseBourgogne-Franche Comté yaseDijon, eFransi Unxibelelwano: Yana ToropovaAlmazov IZiko loPhando lwezoNyango leSizwe, kwiSebe lezeMpilo leRussian Federation, eSaint-Petersburg, 197341, kwiRussian Federation Ucingo +7 981 95264800 4997069 I-imeyile [email protected] Imvelaphi: Indlela ethembisayo kwingxaki yetyhefu ye-cytostatic kukusetyenziswa kwe-magnetic nanoparticles (MNP) ekuhanjisweni kwamayeza ajoliswe kuwo. Injongo: Ukusebenzisa izibalo ukumisela iimpawu ezilungileyo ze-magnetic field elawula ii-MNPs kwi-vivo, kunye nokuvavanya ukusebenza kakuhle kokuhanjiswa kwe-magnetron kwee-MNPs kwi-tumor yegundane kwi-vitro nakwi-vivo. (MNPs-ICG) isetyenziswa. Izifundo zobunzulu bokukhanya kwi-vivo zenziwe kwiimpuku ze-tumor, ezine-magnetic field kunye nezingenayo kwindawo ezinomdla kuyo. Ezi zifundo zenziwe kwi-scaffold ye-hydrodynamic eyenziwe yi-Institute of Experimental Medicine ye-Almazov State Medical Research Center ye-Russian Ministry of Health. Isiphumo: Ukusetyenziswa kweemagnethi ze-neodymium kwakhuthaza ukuqokelelwa kwe-MNP ngokukhetha. Umzuzu omnye emva kokunikezelwa kwe-MNPs-ICG kwiimpuku ezine-tumor, i-MNPs-ICG iqokelelana kakhulu esibindini. Ukuba akukho magnetic field kwaye akukho, oku kubonisa indlela yayo ye-metabolic. Nangona ukwanda kwe-fluorescence kwi-tumor kwabonwa xa kukho magnetic field, ubunzulu be-fluorescence kwisibindi sesilwanyana abuzange butshintshe ngokuhamba kwexesha. Isiphelo: Olu hlobo lwe-MNP, kunye namandla e-magnetic field abaliweyo, lunokuba sisiseko sophuhliso lokuhanjiswa kwamayeza e-cytostatic alawulwa yimagnethi kwizicubu ze-tumor. Amagama angundoqo: uhlalutyo lwe-fluorescence, i-indocyanine, i-iron oxide nanoparticles, ukuhanjiswa kwe-magnetron ye-cytostatics, ukujoliswa kwe-tumor
Izifo zethumba zezinye zezona zinto zibangela ukufa kwihlabathi liphela. Kwangaxeshanye, iindlela zokwanda kokugula nokufa kwezifo zethumba zisekho. 1 I-chemotherapy esetyenziswa namhlanje iseyenye yezona ndlela ziphambili zonyango lweethumba ezahlukeneyo. Kwangaxeshanye, uphuhliso lweendlela zokunciphisa ubuthi be-cytostatics lusabalulekile. Indlela ethembisayo yokusombulula ingxaki yayo yobuthi kukusebenzisa abathwali be-nano-scale ukujolisa kwiindlela zokuhambisa amayeza, ezinokubonelela ngokuqokelelwa kwamayeza kwindawo ethile kwizicubu zethumba ngaphandle kokwandisa ukuqokelelwa kwawo kwizicubu eziphilileyo. 2 Le ndlela yenza kube nokwenzeka ukuphucula ukusebenza kakuhle kunye nokujoliswa kwamayeza e-chemotherapy kwizicubu zethumba, ngelixa kunciphisa ubuthi bawo be-systemic.
Phakathi kwee-nanoparticles ezahlukeneyo eziqwalaselwayo ekuhanjisweni kwee-cytostatic agents ekujoliswe kuzo, ii-magnetic nanoparticles (MNPs) zinomdla kakhulu ngenxa yeempawu zazo ezikhethekileyo zekhemikhali, zebhayoloji, kunye nezemagnethi, eziqinisekisa ukuguquguquka kwazo. Ke ngoko, ii-magnetic nanoparticles zingasetyenziswa njengenkqubo yokufudumeza ukunyanga ii-tumor ezine-hyperthermia (magnetic hyperthermia). Zingasetyenziswa njengee-agents zokuxilonga (magnetic resonance diagnosis). 3-5 Ukusebenzisa ezi mpawu, kunye nokwenzeka kokuqokelelwa kwe-MNP kwindawo ethile, ngokusebenzisa intsimi yemagnethi yangaphandle, ukuhanjiswa kwamalungiselelo eyeza ajoliswe kuwo kuvula ukudalwa kwenkqubo yemagnetron esebenza ngeendlela ezininzi ukujolisa kwi-cytostatics kwindawo yethumba Amathemba. Inkqubo enjalo iya kubandakanya i-MNP kunye neentsimi zemagnethi ukulawula intshukumo yazo emzimbeni. Kule meko, zombini iintsimi zemagnethi zangaphandle kunye nee-implants zemagnethi ezibekwe kwindawo yomzimba equlethe ithumba zingasetyenziswa njengomthombo wentsimi yemagnethi. 6 Indlela yokuqala ineziphene ezinkulu, kubandakanya imfuneko yokusebenzisa izixhobo ezikhethekileyo zokujolisa amayeza ngemagnethi kunye nesidingo sokuqeqesha abasebenzi ukuba benze utyando. Ukongeza, le ndlela inqunyelwe yindleko ephezulu kwaye ifanelekile kuphela kwiithumba "ezingaphandle" ezikufutshane nomphezulu womzimba. Enye indlela yokusebenzisa ii-implants zemagnethi yandisa ububanzi bokusetyenziswa kobu buchwepheshe, iququzelela ukusetyenziswa kwayo kwiithumba ezikwiindawo ezahlukeneyo zomzimba. Zombini iimagnethi kunye neemagnethi ezidityaniswe kwi-intraluminal stent zingasetyenziswa njengee-implants zomonakalo wethumba kwizitho ezingenanto ukuqinisekisa ukuba ziyakwazi ukusebenza. Nangona kunjalo, ngokophando lwethu olungapapashwanga, ezi azinamagnethi ngokwaneleyo ukuqinisekisa ukugcinwa kwe-MNP egazini.
Ukusebenza kakuhle kokuhanjiswa kweziyobisi zemagnetron kuxhomekeke kwizinto ezininzi: iimpawu zomthwali wemagnethi ngokwawo, kunye neempawu zomthombo wemagnethi (kubandakanya iiparameter zejometri zeemagnethi ezisisigxina kunye namandla emagnethi azivelisayo). Uphuhliso lwetekhnoloji yokuhanjiswa kwe-magnetic cell inhibitor ephumelelayo kufuneka ibandakanye uphuhliso lwe-magnetic nanoscale drug carriers ezifanelekileyo, ukuvavanya ukhuseleko lwazo, kunye nokuphuhlisa iprotokholi yokubona evumela ukulandelela iintshukumo zazo emzimbeni.
Kolu phononongo, sibale ngokwezibalo iimpawu ezifanelekileyo zentsimi yemagnethi ukulawula isithwali seziyobisi se-magnetic nano-scale emzimbeni. Amathuba okugcina i-MNP eludongeni lwemithambo yegazi phantsi kwempembelelo yentsimi yemagnethi esetyenzisiweyo enezi mpawu zokubala nawo afundwe kwimithambo yegazi yegundane ehlukanisiweyo. Ukongeza, sidibanise ii-conjugates ze-MNPs kunye nee-fluorescent agents kwaye saphuhlisa iprotokholi yokubonakala kwazo kwi-vivo. Phantsi kweemeko ze-in vivo, kwiimpuku zemodeli ye-tumor, ukusebenza kakuhle kwe-MNPs kwizicubu ze-tumor xa zisetyenziswa ngokwenkqubo phantsi kwempembelelo yentsimi yemagnethi kufundwe.
Kwisifundo se-in vitro, sisebenzise i-reference MNP, kwaye kwisifundo se-in vivo, sisebenzise i-MNP egqunywe yi-lactic acid polyester (i-polylactic acid, i-PLA) equlethe i-fluorescent agent (indolecyanine; ICG). I-MNP-ICG ifakiwe kwimeko, sebenzisa (MNP-PLA-EDA-ICG).
Iimpawu zokwenziwa kunye neempawu zomzimba nezekhemikhali ze-MNP zichazwe ngokweenkcukacha kwenye indawo.
Ukuze kwenziwe i-MNPs-ICG, kwaqala kwaveliswa ii-conjugates ze-PLA-ICG. Kwasetyenziswa umxube we-powder racemic we-PLA-D kunye ne-PLA-L onobunzima be-molecular obuyi-60 kDa.
Ekubeni i-PLA kunye ne-ICG zombini ziyi-asidi, ukuze kwenziwe i-PLA-ICG conjugates, kufuneka kuqala kwenziwe i-amino-terminated spacer kwi-PLA, enceda i-ICG chemisorb kwi-spacer. I-spacer yenziwe kusetyenziswa i-ethylene diamine (EDA), indlela ye-carbodiimide kunye ne-water-soluble carbodiimide, i-1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDAC). I-PLA-EDA spacer yenziwe ngolu hlobo lulandelayo. Yongeza i-EDA engaphezulu kwe-molar ka-20 kunye ne-EDAC engaphezulu kwe-molar ka-20 kwi-2 mL yesisombululo se-0.1 g/mL se-PLA chloroform. Ukwenziwa kwenziwe kwityhubhu yovavanyo ye-polypropylene ye-15 mL kwi-shaker ngesantya se-300 min-1 iiyure ezi-2. I-synthesis scheme iboniswe kuMfanekiso 1. Phinda ukwenziwa ngee-reagents ezingaphezulu ka-200 ukuze uphucule i-synthesis scheme.
Ekupheleni kokwenziwa, isisombululo safakwa kwi-centrifuge ngesantya se-3000 min-1 imizuzu emi-5 ukususa izinto eziphuma kwi-polyethylene ezigqithisileyo. Emva koko, i-2 mL yesisombululo se-0.5 mg/mL se-ICG kwi-dimethyl sulfoxide (DMSO) yongezwa kwisisombululo se-2 mL. I-agitator iqiniswe ngesantya sokuxubha se-300 min-1 iiyure ezi-2. Umzobo we-schematic we-conjugate efunyenweyo uboniswe kuMfanekiso 2.
Kwi-200 mg ye-MNP, songeze i-4 mL PLA-EDA-ICG conjugate. Sebenzisa i-LS-220 shaker (LOIP, eRashiya) ukuze uvuse i-suspension imizuzu engama-30 rhoqo kwi-300 min-1. Emva koko, yahlanjwa nge-isopropanol kathathu yaza yahlulwa ngemagnethi. Sebenzisa i-UZD-2 Ultrasonic Disperser (FSUE NII TVCH, eRashiya) ukongeza i-IPA kwi-suspension imizuzu emi-5-10 phantsi kwesenzo se-ultrasonic esiqhubekayo. Emva kokuhlamba kwesithathu kwe-IPA, i-precipitate yahlanjwa ngamanzi acocekileyo yaza yaphinda yaxhonywa kwi-physiological saline kuxinzelelo lwe-2 mg/mL.
Izixhobo zeZetaSizer Ultra (eMalvern Instruments, e-UK) zisetyenzisiwe ukufunda ukusasazwa kobungakanani be-MNP efunyenweyo kwisisombululo samanzi. I-transmission electron microscope (TEM) ene-JEM-1400 STEM field emission cathode (JEOL, eJapan) isetyenzisiwe ukufunda imo kunye nobukhulu be-MNP.
Kolu phononongo, sisebenzisa iimagnethi ezisisigxina ze-cylindrical (udidi lwe-N35; ezine-nickel protective coating) kunye nobukhulu obulandelayo obuqhelekileyo (ubude be-axis ende × ububanzi be-cylinder): 0.5×2 mm, 2×2 mm, 3×2 mm kunye ne-5×2 mm.
Uphononongo lwe-in vitro lokuthuthwa kwe-MNP kwinkqubo yomzekelo lwenziwe kwi-scaffold ye-hydrodynamic eyenziwe yi-Institute of Experimental Medicine ye-Almazov State Medical Research Center ye-Russian Ministry of Health. Umthamo wolwelo olujikelezayo (amanzi anyibilikisiweyo okanye isisombululo se-Krebs-Henseleit) yi-225 mL. Iimagnethi ze-cylindrical ezi-Axially magnetized zisetyenziswa njengemagnethi ezisisigxina. Beka imagnethi kwisibambi 1.5 mm kude nodonga lwangaphakathi lwetyhubhu yeglasi ephakathi, isiphelo sayo sijonge kwicala letyhubhu (ethe nkqo). Izinga lokuhamba kolwelo kwi-closed loop yi-60 L/h (elihambelana nesantya esithe ngqo se-0.225 m/s). Isisombululo se-Krebs-Henseleit sisetyenziswa njengolwelo olujikelezayo kuba luyi-analog ye-plasma. I-dynamic viscosity coefficient ye-plasma yi-1.1–1.3 mPa∙s. 9 Ubungakanani be-MNP obufakwe kwi-magnetic field bumiselwa yi-spectrophotometry ukusuka kuxinzelelo lwesinyithi kulwelo olujikelezayo emva kovavanyo.
Ukongeza, izifundo zovavanyo zenziwe kwitheyibhile ye-fluid mechanics ephuculweyo ukuze kuchongwe ukuvuleka kwemithambo yegazi. Izinto eziphambili zenkxaso ye-hydrodynamic ziboniswe kuMfanekiso 3. Izinto eziphambili ze-hydrodynamic stent yi-closed loop elinganisa i-cross-section yenkqubo ye-vascular yemodeli kunye netanki yokugcina. Ukuhamba kolwelo lwemodeli ecaleni kwe-contour ye-blood vessel module kunikezelwa yi-peristaltic pump. Ngexesha lovavanyo, gcina umphunga kunye nobubanzi bobushushu obufunekayo, kwaye ujonge iiparameter zenkqubo (ubushushu, uxinzelelo, izinga lokuhamba kolwelo, kunye nexabiso le-pH).
Umfanekiso 3 Umzobo webhloko yendlela esetyenzisiweyo ukufunda ukuvuleka kodonga lwe-carotid artery. Itanki yokugcina eyi-1, ipompo ye-peristaltic eyi-2, indlela ye-3 yokufaka i-suspension equlethe i-MNP kwi-loop, imitha ye-flow eyi-4, i-sensor yoxinzelelo olu-5 kwi-loop, i-exchanger yobushushu eyi-6, igumbi eli-7 elinesikhongozeli, i-8-umthombo we-magnetic field, i-9-ibhaluni ene-hydrocarbons.
Igumbi eliqulathe isitya linezikhongozeli ezintathu: isitya esikhulu sangaphandle kunye nezikhongozeli ezimbini ezincinci, apho iingalo zesekethe ephakathi zidlula khona. I-cannula ifakwa kwisitya esincinci, isitya sibotshelelwe kwisitya esincinci, kwaye incam ye-cannula ibotshelelwe ngokuqinileyo ngentambo encinci. Isithuba esiphakathi kwesitya esikhulu kunye nesitya esincinci sizaliswe ngamanzi acocekileyo, kwaye ubushushu buhlala bungaguquki ngenxa yoqhagamshelo kwi-heat exchanger. Isithuba kwisitya esincinci sizaliswe ngesisombululo seKrebs-Henseleit ukugcina ukusebenza kweeseli zemithambo yegazi. Itanki ikwazaliswe ngesisombululo seKrebs-Henseleit. Inkqubo yokubonelela ngegesi (ikhabhoni) isetyenziselwa ukufutha isisombululo kwisitya esincinci kwitanki yokugcina kunye negumbi eliqulathe isitya (Umfanekiso 4).
Umfanekiso 4 Igumbi apho isitya sibekwe khona. 1-I-Cannula yokwehlisa imithambo yegazi, 2-Igumbi langaphandle, 3-Igumbi elincinci. Utolo lubonisa icala lolwelo lomzekelo.
Ukufumanisa isalathisi sokuvuleka kodonga lwemithambo yegazi, kusetyenziswe umthambo we-rat carotid.
Ukungeniswa kwe-MNP suspension (0.5mL) kwinkqubo kuneempawu ezilandelayo: umthamo wangaphakathi wetanki kunye nombhobho wokudibanisa kwi-loop yi-20mL, kwaye umthamo wangaphakathi wegumbi ngalinye yi-120mL. Umthombo wangaphandle wemagnethi yimagnethi esisigxina enobukhulu obuqhelekileyo be-2×3 mm. Ifakwe ngaphezulu kwelinye lamagumbi amancinci, i-1 cm ukusuka kwisikhongozeli, kwaye isiphelo esinye sijonge eludongeni lwesikhongozeli. Ubushushu bugcinwa kwi-37°C. Amandla epompo yeroller amiselwe kwi-50%, ehambelana nesantya se-17 cm/s. Njengolawulo, iisampulu zithathwe kwiseli engenamagnethi esisigxina.
Emva kweyure enye yokunikwa koxinzelelo oluthile lwe-MNP, isampuli yolwelo yathathwa kwigumbi. Uxinzelelo lwamasuntswana lwalinganiswa nge-spectrophotometer kusetyenziswa i-Unico 2802S UV-Vis spectrophotometer (United Products & Instruments, USA). Xa kujongwa i-absorption spectrum ye-MNP suspension, umlinganiselo wenziwe kwi-450 nm.
Ngokwezikhokelo zeRus-LASA-FELASA, zonke izilwanyana zikhuliswa kwaye zikhuliswe kwiindawo ezithile ezingenazo iintsholongwane. Olu phononongo luhambelana nayo yonke imithetho yokuziphatha efanelekileyo yovavanyo lwezilwanyana kunye nophando, kwaye lufumene imvume yokuziphatha kwi-Almazov National Medical Research Center (IACUC). Izilwanyana zazisela amanzi ngokukhawuleza kwaye zondliwa rhoqo.
Olu phononongo lwenziwe kwiimpuku ezili-10 ze-NSG ezingamadoda ezineeveki ezili-12 ubudala ezingasebenzi kakuhle emzimbeni (NOD.Cg-Prkdcscid Il2rgtm1Wjl/Szj, Jackson Laboratory, USA) 10, ezinobunzima obuyi-22 g ± 10%. Ekubeni ukhuseleko lwempuku ezingasebenzi kakuhle emzimbeni lucinezelwe, iimpuku ezingasebenzi kakuhle emzimbeni zale migca zivumela ukufakelwa kweeseli kunye nezicubu zabantu ngaphandle kokulahlwa kokufakelwa. Iimpuku ezihlala kunye ezivela kwiikheyiji ezahlukeneyo zabelwa ngokungacwangciswanga kwiqela lovavanyo, kwaye zazaliswa kunye okanye zavezwa ngokucwangcisiweyo kwiibhedi zamanye amaqela ukuqinisekisa ukuba zichaphazeleka ngokulinganayo kwi-microbiota eqhelekileyo.
Umgca weeseli zomhlaza womntu we-HeLa usetyenziselwa ukuseka imodeli ye-xenograft. Iiseli zakhuliswa kwi-DMEM equlethe i-glutamine (i-PanEco, eRashiya), yongezwa nge-10% ye-fetal bovine serum (i-Hyclone, e-USA), i-100 CFU/mL penicillin, kunye ne-100 μg/mL streptomycin. Umgca weseli wanikezelwa ngobubele yi-Gene Expression Regulation Laboratory ye-Institute of Cell Research ye-Russian Academy of Sciences. Ngaphambi kokufakwa, iiseli ze-HeLa zasuswa kwiplastiki yokukhulisa ngesisombululo se-1:1 trypsin:Versene (i-Biolot, eRashiya). Emva kokuhlamba, iiseli zaxhonywa kwindawo ephakathi ukuya kuxinzelelo lweeseli ezi-5×106 kwi-200 μL nganye, zaza zaxutywa nge-basement membrane matrix (LDEV-FREE, MATRIGEL® CORNING®) (1:1, kwiqhwa). Ukumiswa kweseli okulungiselelweyo kwafakwa ngaphantsi kwesikhumba sethanga lempuku. Sebenzisa ii-calipers ze-elektroniki ukujonga ukukhula kwethumba rhoqo kwiintsuku ezi-3.
Xa ithumba lifikelela kwi-500 mm3, imagnethi esisigxina yafakwa kwizicubu zemisipha yesilwanyana esivavanyiweyo kufutshane nethumba. Kwiqela lovavanyo (i-MNPs-ICG + i-tumor-M), i-0.1 mL ye-MNP suspension yafakwa yaza yavezwa kwindawo yemagnethi. Izilwanyana ezipheleleyo ezinganyangwanga zasetyenziswa njengezilawuli (imvelaphi). Ukongeza, izilwanyana ezifakwe i-0.1 mL ye-MNP kodwa ezingafakwanga iimagnethi (i-MNPs-ICG + i-tumor-BM) zasetyenziswa.
Ukuboniswa kwe-fluorescence kweesampuli ze-in vivo kunye ne-in vitro kwenziwe kwi-IVIS Lumina LT series III bioimager (PerkinElmer Inc., e-USA). Kwi-in visualization, umthamo we-1 mL we-synthetic PLA-EDA-ICG kunye ne-MNP-PLA-EDA-ICG conjugate yongezwe kwi-plate wells. Xa kujongwa iimpawu ze-fluorescence zedayi ye-ICG, kukhethwe isihluzi esifanelekileyo esisetyenziselwa ukumisela i-luminous intensity yesampuli: ubude be-excitation obukhulu yi-745 nm, kwaye ubude be-emission yi-815 nm. Isoftware ye-Living Image 4.5.5 (PerkinElmer Inc.) yasetyenziswa ukulinganisa i-fluorescence intensity ye-wells equlethe i-conjugate ngokwenani.
Ubunzulu be-fluorescence kunye nokuqokelelwa kwe-conjugate ye-MNP-PLA-EDA-ICG kulinganiswe kwiimpuku zemodeli ye-tumor in vivo, ngaphandle kobukho kunye nokusetyenziswa kwe-magnetic field kwindawo enomdla kuyo. Iimpuku zahlanjwa nge-isoflurane, kwaye emva koko i-0.1 mL ye-conjugate ye-MNP-PLA-EDA-ICG yafakwa nge-tail vein. Iimpuku ezinganyangwanga zasetyenziswa njengolawulo olungalunganga ukuze zifumane imvelaphi ye-fluorescent. Emva kokusebenzisa i-conjugate nge-intravenous, beka isilwanyana kwisigaba sokufudumeza (37°C) kwigumbi le-IVIS Lumina LT series III fluorescence imager (PerkinElmer Inc.) ngelixa ugcina ukuphefumla nge-2% isoflurane anaesthetization. Sebenzisa isihluzi esakhelwe ngaphakathi se-ICG (745–815 nm) ukuze ufumane isignali umzuzu o-1 kunye nemizuzu eli-15 emva kokungeniswa kwe-MNP.
Ukuvavanya ukuqokelelwa kwe-conjugate kwi-tumor, indawo ye-peritoneal yesilwanyana yayigqunywe ngephepha, nto leyo eyenza ukuba kube nokwenzeka ukuphelisa ukukhanya okukhanyayo okunxulunyaniswa nokuqokelelwa kwamasuntswana esibindini. Emva kokufunda ngokusasazwa kwe-MNP-PLA-EDA-ICG, izilwanyana zabulawa ngobuntu ngokugqithisileyo kwe-isoflurane anesthesia ukuze kwahlulwe iindawo ze-tumor kunye novavanyo lobungakanani bemitha ye-fluorescence. Sebenzisa isoftware ye-Living Image 4.5.5 (PerkinElmer Inc.) ukuze ucubungule uhlalutyo lwesignali ngesandla ukusuka kummandla okhethiweyo onomdla. Kwathathwa amanyathelo amathathu kwisilwanyana ngasinye (n = 9).
Kolu phononongo, asizange silinganise ukulayisha ngempumelelo kwe-ICG kwi-MNPs-ICG. Ukongeza, asizange sithelekise ukusebenza kakuhle kokugcinwa kwee-nanoparticles phantsi kwempembelelo yeemagnethi ezihlala zihleli zeemilo ezahlukeneyo. Ukongeza, asizange sivavanye isiphumo sexesha elide se-magnetic field ekugcinweni kwee-nanoparticles kwizicubu zethumba.
Ii-nanoparticles zilawula, ngobukhulu obuphakathi kwe-195.4 nm. Ukongeza, i-suspension yayinee-agglomerates ezinobukhulu obuphakathi kwe-1176.0 nm (Umfanekiso 5A). Emva koko, inxalenye yahluzwa ngesihluzi se-centrifugal. Amandla e-zeta ee-particles yi--15.69 mV (Umfanekiso 5B).
Umfanekiso 5 Iimpawu ezibonakalayo zokumiswa: (A) ukusasazwa kobungakanani besuntswana; (B) ukusasazwa kwesuntswana kwi-zeta potential; (C) Umfanekiso we-TEM wee-nanoparticles.
Ubungakanani besuntswana buyi-200 nm (Umfanekiso 5C), obunjwe yi-MNP enye enobukhulu obuyi-20 nm, kunye negobolondo le-PLA-EDA-ICG elidityanisiweyo elinobunzima obuphantsi be-electron. Ukwakheka kwee-agglomerates kwizisombululo zamanzi kunokuchazwa yi-modulus ephantsi kakhulu yamandla e-electromotive e-nanoparticles nganye.
Kwimagnethi ezisisigxina, xa imagnetization igxininiswe kwivolumu V, ukubonakaliswa okuhlanganisiweyo kwahlulwe kwaba zii-integrals ezimbini, ezizezi ivolumu kunye nomphezulu:
Kwimeko yesampulu enemagnetization engaguqukiyo, uxinano lwangoku luyi-zero. Emva koko, ukubonakaliswa kwevektha ye-magnetic induction kuya kuthatha le ndlela ilandelayo:
Sebenzisa inkqubo yeMATLAB (iMathWorks, Inc., e-USA) yokubala amanani, inombolo yelayisenisi yezemfundo ye-ETU “LETI” engu-40502181.
Njengoko kubonisiwe kuMfanekiso 7 Umfanekiso 8 Umfanekiso 9 Umfanekiso-10, intsimi yemagnethi enamandla iveliswa yimagnethi ejolise kwi-axially ukusuka esiphelweni sesilinda. Irediyasi esebenzayo yesenzo ilingana nejometri yemagnethi. Kwiimagnethi zesilinda ezinesilinda ezinobude obungaphezulu kobubanzi bayo, intsimi yemagnethi enamandla ibonwa kwicala le-axial-radial (kwicandelo elihambelanayo); ke ngoko, isibini seesilinda ezinomlinganiselo omkhulu (ububanzi kunye nobude) i-MNP adsorption yeyona isebenzayo.
Umzobo 7 Inxalenye ye-magnetic induction intensity Bz ecaleni kwe-Oz axis yemagnethi; ubungakanani obuqhelekileyo bemagnethi: umgca omnyama 0.5×2mm, umgca oluhlaza okwesibhakabhaka 2×2mm, umgca oluhlaza okwesibhakabhaka 3×2mm, umgca obomvu 5×2mm.
Umfanekiso 8 Icandelo le-magnetic induction Br lithe nkqo kwi-magnet axis Oz; ubungakanani obuqhelekileyo bemagnethi: umgca omnyama 0.5×2mm, umgca oluhlaza okwesibhakabhaka 2×2mm, umgca oluhlaza okwesibhakabhaka 3×2mm, umgca obomvu 5×2mm.
Umfanekiso 9 Inxalenye ye-Bz yobunzulu bokungenisa amandla emagnethi kumgama ongu-r ukusuka kwi-axis yokugqibela yemagnethi (z=0); ubungakanani obuqhelekileyo bemagnethi: umgca omnyama ongu-0.5×2mm, umgca oluhlaza okwesibhakabhaka ongu-2×2mm, umgca oluhlaza ongu-3×2mm, umgca obomvu ongu-5×2mm.
Umfanekiso 10 Icandelo lokungenisa imagnethi kwicala le-radial; ubungakanani obuqhelekileyo bemagnethi: umgca omnyama 0.5×2mm, umgca oluhlaza okwesibhakabhaka 2×2mm, umgca oluhlaza 3×2mm, umgca obomvu 5×2mm.
Iimodeli ezikhethekileyo ze-hydrodynamic zingasetyenziselwa ukufunda indlela yokuhanjiswa kwe-MNP kwizicubu zethumba, ukugxininisa ii-nanoparticles kwindawo ekujoliswe kuyo, kunye nokuchonga indlela yokuziphatha kwee-nanoparticles phantsi kweemeko ze-hydrodynamic kwinkqubo yokujikeleza kwegazi. Iimagnethi ezisisigxina zingasetyenziswa njengeendawo zangaphandle zemagnethi. Ukuba asiyinaki intsebenziswano ye-magnetostatic phakathi kwee-nanoparticles kwaye singayicingi imodeli ye-magnetic fluid, kwanele ukuqikelela intsebenziswano phakathi kwemagnethi kunye ne-nanoparticle enye ene-dipole-dipole approximation.
Apho u-m lixesha lemagnethi lemagnethi, u-r yi-radius vector yendawo apho i-nanoparticle ikhoyo, kwaye u-k yi-system factor. Kwi-dipole approximation, intsimi yemagnethi inoqwalaselo olufanayo (Umfanekiso 11).
Kwintsimi yemagnethi efanayo, ii-nanoparticles zijikeleza kuphela kwimigca yamandla. Kwintsimi yemagnethi engalinganiyo, amandla asebenza kuyo:
Iphi i-derivative yesalathiso esinikiweyo l. Ukongeza, amandla atsala ii-nanoparticles kwiindawo ezingalinganiyo zentsimi, oko kukuthi, ukugoba kunye noxinano lwemigca yamandla luyanda.
Ngoko ke, kuyacetyiswa ukusebenzisa imagnethi enamandla ngokwaneleyo (okanye itshaneli yemagnethi) ene-anisotropy ecacileyo ye-axial kwindawo apho amasuntswana akhoyo khona.
Itheyibhile 1 ibonisa amandla emagnethi enye njengomthombo owaneleyo wentsimi yemagnethi ukubamba nokugcina i-MNP kwindawo yemithambo yegazi yentsimi yesicelo.