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Lawula ukunyakaza kwe-magnetic iron oxide nanoparticles ukulethwa okuhlosiwe kwama-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 Isikhungo Sokucwaninga soMnyango Wezempilo waseRussian Federation, eSt. Petersburg, ngo-197341, Russian Federation;2 St. Petersburg Electrotechnical University “LETI”, St. Petersburg, 197376, Russian Federation;3 Centre for Personalized Medicine, Almazov State Medical Research Center, Ministry of Health of the Russian Federation, St. Petersburg, 197341, Russia Federation;4FSBI “Influenza Research Institute eqanjwe ngo-AA Smorodintsev” Ministry of Health of the Russian Federation, St. Petersburg, Russian 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, Faculty of Medicine and Pharmacy, Bourgogne-Franche Comté University of Dijon, France Communication: Yana ToropovaAlmazov National Medical Research Centre, Ministry of Health of the Russian Federation, Saint-Petersburg, 197341, Russian Federation Tel +7 981 952694800 952694800 [i-imeyili ivikelwe] Isendlalelo: Indlela ethembisayo enkingeni yobuthi be-cytostatic ukusetshenziswa kwe-magnetic nanoparticles (MNP) ekulethweni kwezidakamizwa okuhlosiwe.Inhloso: Ukusebenzisa izibalo ukuze kutholwe izici ezinhle kakhulu zenkundla kazibuthe elawula ama-MNP ku-vivo, kanye nokuhlola ukusebenza kahle kokulethwa kwe-magnetron kwama-MNP kumathumba egundane ku-vitro kanye ne-vivo.(MNPs-ICG) isetshenziswa.Izifundo ze-in vivo luminescence intensity zenziwa kumagundane esimila, ngaphandle nangaphandle kwenkundla kazibuthe endaweni yentshisekelo.Lezi zifundo zenziwa ku-scaffold ye-hydrodynamic eyakhiwe yi-Institute of Experimental Medicine ye-Almazov State Medical Research Center yoMnyango Wezempilo waseRussia.Umphumela: Ukusetshenziswa kozibuthe be-neodymium kukhuthaze ukuqoqwa okukhethekile kwe-MNP.Umzuzu owodwa ngemva kokuphathwa kwe-MNPs-ICG kumagundane aphethe isimila, i-MNPs-ICG ikakhulukazi inqwabelana esibindini.Uma kungekho kanye nokuba khona kwensimu kazibuthe, lokhu kubonisa indlela yayo ye-metabolic.Nakuba ukwanda kwe-fluorescence ku-tumor kwabonwa lapho kukhona insimu kazibuthe, amandla e-fluorescence esibindi sesilwane azange ashintshe ngokuhamba kwesikhathi.Isiphetho: Lolu hlobo lwe-MNP, oluhlanganiswe namandla kazibuthe abaliwe, lungaba isisekelo sokuthuthukiswa kokulethwa okulawulwa ngozibuthe kwezidakamizwa ze-cytostatic ezicutshini zesimila.Amagama angukhiye: ukuhlaziywa kwe-fluorescence, i-indocyanine, i-iron oxide nanoparticles, ukulethwa kwe-magnetron kwe-cytostatics, ukuqondiswa kwesimila
Izifo zesimila zingenye yezimbangela eziyinhloko zokufa emhlabeni jikelele.Ngesikhathi esifanayo, ukuguquguquka kokwanda kokugula nokufa kwezifo zesimila kusekhona.1 Ukwelashwa ngamakhemikhali okusetshenziswa namuhla kusengenye yezindlela zokwelapha eziyinhloko zamathumba ahlukene.Ngesikhathi esifanayo, ukuthuthukiswa kwezindlela zokunciphisa ubuthi obuhlelekile be-cytostatics kusabalulekile.Indlela ethembisayo yokuxazulula inkinga yayo yobuthi ukusebenzisa abathwali be-nano-scale ukukhomba izindlela zokulethwa kwezidakamizwa, ezinganikeza ukuqoqwa kwendawo kwezidakamizwa ezicutshini zesimila ngaphandle kokwandisa ukunqwabelana kwazo ezithweni ezinempilo nezicubu.ukugxilisa ingqondo.2 Le ndlela yenza kube nokwenzeka ukuthuthukisa ukusebenza kahle kanye nokuqondiswa kwezidakamizwa ze-chemotherapeutic ezicutshini zesimila, kuyilapho kunciphisa ubuthi bazo besistimu.
Phakathi kwama-nanoparticles ahlukahlukene acatshangelwa ukulethwa okuhlosiwe kwama-cytostatic agents, ama-nanoparticles kazibuthe (MNPs) anentshisekelo ethile ngenxa yezindawo zawo eziyingqayizivele zamakhemikhali, zebhayoloji, kanye nezikazibuthe, eziqinisekisa ukuhlukahluka kwazo.Ngakho-ke, ama-nanoparticles kazibuthe angasetshenziswa njengendlela yokushisa yokwelapha amathumba nge-hyperthermia (magnetic hyperthermia).Zingasetshenziswa futhi njengama-ejenti okuxilonga (ukuxilongwa kwe-magnetic resonance).I-3-5 Ukusebenzisa lezi zici, kuhlangene nethuba lokuqoqwa kwe-MNP endaweni ethile, ngokusebenzisa inkambu yamagnetic yangaphandle, ukulethwa kwamalungiselelo emithi okuhlosiwe kuvula ukwakhiwa kwesistimu ye-magnetron esebenzayo ukuze iqondise i-cytostatics endaweni yesimila. Amathemba.Uhlelo olunjalo luzobandakanya i-MNP nezizibuthe zokulawula ukunyakaza kwazo emzimbeni.Kulokhu, kokubili izinkambu kazibuthe zangaphandle kanye nezimila kazibuthe ezibekwe endaweni yomzimba equkethe isimila zingasetshenziswa njengomthombo wensimu kazibuthe.6 Indlela yokuqala inamaphutha amakhulu, okuhlanganisa isidingo sokusebenzisa izinto ezikhethekile zokukhomba izidakamizwa kazibuthe kanye nesidingo sokuqeqesha izisebenzi ukuba zihlinze.Ngaphezu kwalokho, le ndlela inqunyelwe izindleko eziphakeme futhi ifaneleka kuphela izimila "eziphezulu" eduze nobuso bomzimba.Enye indlela yokusebenzisa izimila kazibuthe yandisa ububanzi bokusetshenziswa kwalobu buchwepheshe, yenze kube lula ukusetshenziswa kwayo kumathumba atholakala ezingxenyeni ezahlukene zomzimba.Kokubili omazibuthe abangabodwana kanye nozibuthe okuhlanganiswe ku-stent ye-intraluminal kungasetshenziswa njengezimila zokulimala kwesimila ezithweni ezingenalutho ukuze kuqinisekiswe amandla azo.Nokho, ngokocwaningo lwethu olungashicilelwe, lezi azikazibuthe ngokwanele ukuqinisekisa ukugcinwa kwe-MNP egazini.
Ukuphumelela kokulethwa kwezidakamizwa ze-magnetron kuncike ezintweni eziningi: izici zenkampani yenethiwekhi kazibuthe ngokwayo, kanye nezici zomthombo wamagnetic field (kuhlanganise nemingcele yejometri yamagnethi ahlala njalo namandla okusebenza kazibuthe abawakhiqizayo).Ukuthuthukiswa kobuchwepheshe bokulethwa kwe-cell inhibitor obuqondiswa kazibuthe obuphumelelayo kufanele kuhilele ukuthuthukiswa kwezinkampani ezithwala izidakamizwa ezizibuthe ze-nanoscale, ukuhlola ukuphepha kwazo, nokwakhiwa kwephrothokholi yokubuka evumela ukulandelela ukunyakaza kwazo emzimbeni.
Kulolu cwaningo, ngokwezibalo sibale izici zensimu kazibuthe ezilungile ukuze silawule umthwali wezidakamizwa ozibuthe we-nano-scale emzimbeni.Amathuba okugcina i-MNP ngodonga lomkhumbi wegazi ngaphansi kwethonya lenkambu kazibuthe esetshenziswayo enalezi zici zokubala futhi yacwaningwa emithanjeni yegazi yamagundane eqhelile.Ngaphezu kwalokho, sihlanganise ama-conjugates ama-MNP nama-ejenti e-fluorescent futhi sathuthukisa isimiso somthetho sokubonwa kwawo ngeso lengqondo ku-vivo.Ngaphansi kwezimo ze-vivo, kumagundane emodeli yesimila, ukusebenza kahle kokunqwabelana kwama-MNP kuzicubu zesimila lapho kulawulwa ngohlelo ngaphansi kwethonya lenkundla kazibuthe kwafundwa.
Ocwaningweni lwe-in vitro, sasebenzisa i-MNP eyinkomba, futhi ocwaningweni lwe-vivo, sasebenzisa i-MNP ehlanganiswe ne-lactic acid polyester (i-polylactic acid, i-PLA) equkethe i-agent ye-fluorescent (indolecyanine; ICG).I-MNP-ICG ifakiwe kokuthi Esimeni, sebenzisa (MNP-PLA-EDA-ICG).
I-synthesis and physical and chemical properties ye-MNP ichazwe kabanzi kwenye indawo.7,8
Ukuze kuhlanganiswe i-MNPs-ICG, izihlanganisi ze-PLA-ICG zaqala ukukhiqizwa.Kusetshenziswe ingxube ye-powder racemic ye-PLA-D ne-PLA-L enesisindo samangqamuzana angama-60 kDa.
Njengoba i-PLA ne-ICG kungama-asidi womabili, ukuze kuhlanganiswe ama-conjugate e-PLA-ICG, kudingeka kuqala kuhlanganiswe i-spacer enqanyuliwe i-amino ku-PLA, esiza i-ICG chemisorb ku-spacer.I-spacer yahlanganiswa kusetshenziswa i-ethylene diamine (EDA), indlela ye-carbodiimide kanye ne-carbodiimide encibilikayo emanzini, i-1-ethyl-3- (3-dimethylaminopropyl) carbodiimide (EDAC).I-PLA-EDA spacer ihlanganiswe kanje.Engeza i-molar ephindwe izikhathi ezingu-20 ye-EDA kanye ne-molar ephindwe ka-20 ye-EDAC ku-2 mL we-0.1 g/mL ye-PLA chloroform solution.Ukuhlanganiswa kwenziwa ngeshubhu yokuhlola ye-polypropylene engu-15 mL ku-shaker ngesivinini esingama-300 min-1 amahora ama-2.I-synthesis scheme iboniswa kuMfanekiso 1. Phinda ukuhlanganisa ngokuphindwe izikhathi ezingu-200 okweqile kwama-reagents ukuze uthuthukise uhlelo lokuhlanganiswa.
Ekupheleni kokuhlanganiswa, isixazululo sasiyi-centrifuged ngesivinini se-3000 min-1 imizuzu engu-5 ukuze kukhishwe okuphuma kwe-polyethylene okweqile.Khona-ke, u-2 mL wesisombululo se-ICG esingu-0.5 mg/mL ku-dimethyl sulfoxide (DMSO) yengezwe kusixazululo esingu-2 mL.I-agitator ihlelwe ngesivinini esishukumisayo se-300 min-1 amahora angu-2.Umdwebo wohlelo lwe-conjugate etholiwe uboniswa kuMfanekiso 2.
Ku-200 mg MNP, sengeze i-conjugate engu-4 mL ye-PLA-EDA-ICG.Sebenzisa i-LS-220 shaker (LOIP, Russia) ukuze uvuselele ukumiswa imizuzu engu-30 ngemvamisa ye-300 min-1.Ngemuva kwalokho, yagezwa nge-isopropanol kathathu futhi yahlukaniswa ngozibuthe.Sebenzisa i-UZD-2 Ultrasonic Disperser (FSUE NII TVCH, Russia) ukwengeza i-IPA ekumisweni kwemizuzu engu-5-10 ngaphansi kwesenzo esiqhubekayo se-ultrasonic.Ngemuva kokugeza kwe-IPA yesithathu, i-precipitate yagezwa ngamanzi a-distilled futhi yaphinde yamiswa ku-saline ye-physiological ekuhlanganiseni kwe-2 mg/mL.
Imishini ye-ZetaSizer Ultra (i-Malvern Instruments, e-UK) yasetshenziselwa ukutadisha ukusabalalisa usayizi we-MNP etholiwe kusixazululo samanzi.I-electronic microscope yokudlulisa (TEM) ene-JEM-1400 STEM field emission cathode (JEOL, Japan) yasetshenziswa ukutadisha ukuma nosayizi we-MNP.
Kulolu cwaningo, sisebenzisa amamagnethi ahlala e-cylindrical (ibanga le-N35; nge-nickel protective coating) kanye namasayizi alandelayo ajwayelekile (ubude be-eksisi ende × ububanzi besilinda): 0.5×2 mm, 2×2 mm, 3×2 mm no-5×2 mm.
Ucwaningo lwe-in vitro lwezokuthutha ze-MNP ohlelweni lwemodeli lwenziwa ku-scaffold ye-hydrodynamic eyakhiwe yi-Institute of Experimental Medicine ye-Almazov State Medical Research Centre yoMnyango Wezempilo waseRussia.Ivolumu yoketshezi olujikelezayo (amanzi acwengekile noma isisombululo se-Krebs-Henseleit) singama-225 mL.Ozibuthe be-axially cylindrical magnetic asetshenziswa njengozibuthe unomphela.Beka umazibuthe esibambini esingu-1.5 mm kude nodonga lwangaphakathi lweshubhu yengilazi emaphakathi, isiphetho saso sibheke lapho kubheke khona ishubhu (ime mpo).Izinga lokugeleza koketshezi ku-loop evaliwe ngu-60 L/h (okuhambisana nesivinini somugqa esingu-0.225 m/s).Isixazululo se-Krebs-Henseleit sisetshenziswa njengoketshezi olujikelezayo ngoba luyi-analog ye-plasma.I-dynamic viscosity coefficient ye-plasma ingu-1.1–1.3 mPa∙s.9 Inani le-MNP elikhangisiwe endaweni kazibuthe linqunywa i-spectrophotometry kusukela ekugxilweni kwensimbi oketshezini olujikelezayo ngemva kokuhlolwa.
Ngaphezu kwalokho, ucwaningo lokuhlola luye lwenziwa kuthebula le-fluid mechanics elithuthukisiwe ukuze kutholwe ukungeneka okuhlobene kwemithambo yegazi.Izingxenye eziyinhloko zokusekelwa kwe-hydrodynamic ziboniswa ku-Figure 3. Izingxenye eziyinhloko ze-hydrodynamic stent ziyi-loop evaliwe elingisa ingxenye yesiphambano sesistimu ye-vascular model kanye ne-tank yokugcina.Ukuhamba koketshezi oluyimodeli eduze kwe-contour yemodyuli yomkhumbi wegazi kunikezwa iphampu ye-peristaltic.Ngesikhathi sokuhlolwa, gcina ukuhwamuka kanye nebanga lokushisa elidingekayo, futhi uqaphe amapharamitha wesistimu (izinga lokushisa, ingcindezi, izinga lokugeleza koketshezi, nevelu ye-pH).
Umfanekiso 3 Ibhulokhi idayagramu yokusetha esetshenziselwa ukutadisha ukungeneka komthambo we-carotid.Ithangi lesitoreji esingu-1, iphampu ye-peristaltic engu-2, indlela engu-3 yokwethula ukumiswa okuqukethe i-MNP kuluphu, imitha yokugeleza okungu-4, inzwa yokucindezela okungu-5 kuluphu, isishintshi sokushisa esingu-6, igumbi lesi-7 elinesitsha , 8-umthombo wensimu kazibuthe, 9-ibhaluni elinama-hydrocarbon.
Igumbi eliqukethe isitsha liqukethe iziqukathi ezintathu: isitsha esikhulu sangaphandle nezitsha ezimbili ezincane, okudlula kuzo izingalo zesekethe emaphakathi.I-cannula ifakwa esitsheni esincane, isitsha sifakwe izintambo esitsheni esincane, futhi isihloko se-cannula siboshwe ngokuqinile ngocingo oluncane.Isikhala phakathi kwesitsha esikhulu kanye nesitsha esincane sigcwele amanzi acwecwe, futhi izinga lokushisa lihlala lihlala njalo ngenxa yokuxhumeka kumshini wokushisa.Isikhala esitsheni esincane sigcwele isisombululo se-Krebs-Henseleit ukuze kugcinwe ukusebenza kwamangqamuzana omkhumbi wegazi.Ithangi liphinde ligcwaliswe ngesisombululo se-Krebs-Henseleit.Uhlelo lokuhlinzeka ngegesi (ikhabhoni) lusetshenziselwa ukuhwamisa isixazululo esitsheni esincane esisethangini lokugcina kanye negumbi eliqukethe isiqukathi (Umfanekiso 4).
Umfanekiso 4 Igumbi lapho isitsha sibekwe khona.1-Cannula yokwehlisa imithambo yegazi, 2-Outer chamber, 3-Igumbi elincane.Umcibisholo ubonisa isiqondiso soketshezi lwemodeli.
Ukuze kunqunywe inkomba yokuvuthwa okuhlobene kodonga lomkhumbi, kusetshenziswe umthambo we-carotid wegundane.
Ukwethulwa kokumiswa kwe-MNP (0.5mL) ohlelweni kunezici ezilandelayo: isamba sevolumu yangaphakathi yethangi nepayipi elixhumayo ku-loop ngu-20mL, futhi umthamo wangaphakathi wegumbi ngalinye ngu-120mL.Umthombo wangaphandle uzibuthe uzibuthe unomphela onosayizi ojwayelekile we-2×3 mm.Ifakwe ngaphezu kwelinye lamakamelo amancane, ibanga elingu-1 cm ukusuka esitsheni, elinye libheke odongeni lwesitsha.Izinga lokushisa ligcinwa ku-37°C.Amandla wepompo ye-roller asethelwe ku-50%, ehambisana nesivinini se-17 cm / s.Njengokulawula, amasampula athathwe esitokisini esingenamazibuthe unomphela.
Ihora elilodwa ngemuva kokuphathwa kokugxiliswa okunikeziwe kwe-MNP, isampula yoketshezi yathathwa egumbini.Ukugxiliswa kwezinhlayiyana kukalwe nge-spectrophotometer kusetshenziswa i-Unico 2802S UV-Vis spectrophotometer (United Products & Instruments, USA).Ngokucabangela i-spectrum yokumuncwa kokumiswa kwe-MNP, ukulinganisa kwenziwa ku-450 nm.
Ngokweziqondiso ze-Rus-LASA-FELASA, zonke izilwane zikhuliswa futhi zikhuliswe ezindaweni ezithile ezingenalo i-pathogen.Lolu cwaningo luthobela yonke imithetho yokuziphatha efanele yokuhlolwa kwezilwane nocwaningo, futhi luthole ukugunyazwa kwezimiso zokuziphatha kwa-Almazov National Medical Research Center (IACUC).Izilwane zaziphuza amanzi ad libitum futhi zondle njalo.
Ucwaningo lwenziwe kumagundane angu-10 anamaviki angu-12 anamaviki angu-12 ayisilisa angakwazi ukuzivikela komzimba (NOD.Cg-Prkdcscid Il2rgtm1Wjl/Szj, Jackson Laboratory, USA) 10, anesisindo esingu-22 g ± 10%.Njengoba ukuzivikela kwamagundane e-immunodeficiency kucindezelwe, amagundane e-immunodeficiency alo mugqa avumela ukufakelwa kwamangqamuzana omuntu kanye nezicubu ngaphandle kokwenqatshwa kokufakelwa.Ama-littermate avela emakhejini ahlukene abelwa ngokungahleliwe eqenjini lokuhlola, futhi akhuliswa ngokuhlanganyela noma avezwa ngokuhlelekile emibhedeni yamanye amaqembu ukuze kuqinisekiswe ukuchayeka okulinganayo ku-microbiota evamile.
I-HeLa human cell cell line isetshenziselwa ukusungula imodeli ye-xenograft.Amaseli akhuliswe ku-DMEM equkethe i-glutamine (i-PanEco, e-Russia), engezwe nge-fetal bovine serum (Hyclone, USA), 100 CFU/mL penicillin, kanye ne-100 μg/mL streptomycin.Ulayini wamaseli wanikezwa ngomusa i-Gene Expression Regulation Laboratory ye-Institute of Cell Research ye-Russian Academy of Sciences.Ngaphambi komjovo, amaseli e-HeLa ayekhishwa epulasitiki yesiko nge-trypsin engu-1:1:isixazululo se-Versene (Biolot, Russia).Ngemva kokuwashwa, amaseli ayemiswa phakathi ngokuphelele ukuya ekuhlanganiseni kwamaseli angu-5×106 ngo-200 μL ngamunye, futhi ahlanjululwa nge-membrane ye-basement matrix (LDEV-FREE, MATRIGEL® CORNING®) (1:1, eqhweni).Ukumiswa kweseli okulungisiwe kwajovwa ngaphansi kwesikhumba ethangeni legundane.Sebenzisa ama-caliper kagesi ukuqapha ukukhula kwesimila njalo ezinsukwini ezi-3.
Lapho isimila sifinyelela ku-500 mm3, kwafakwa uzibuthe ongunaphakade esicutshini semisipha yesilwane esihlolwayo eduze kwesimila.Eqenjini lokuhlola (MNPs-ICG + tumor-M), 0.1 mL yokumiswa kwe-MNP yajovwa futhi yavezwa endaweni kazibuthe.Izilwane ezingalashiwe eziphelele zazisetshenziswa njengezilawuli (isizinda).Ukwengeza, izilwane ezijovwe ngo-0.1 mL we-MNP kodwa ezingafakwanga ngozibuthe (MNPs-ICG + tumor-BM) zasetshenziswa.
Ukubukwa kwe-fluorescence kwamasampuli e-vivo kanye ne-in vitro kwenziwa kuchungechunge lwe-IVIS Lumina LT III bioimager (PerkinElmer Inc., USA).Ngokubukwa kwe-in vitro, umthamo we-1 mL we-synthetic PLA-EDA-ICG kanye ne-MNP-PLA-EDA-ICG conjugate yengezwe emithonjeni yamapuleti.Ngokucabangela izici ze-fluorescence zodayi we-ICG, isihlungi esingcono kakhulu esisetshenziselwa ukunquma amandla okukhanya kwesampula sikhethiwe: ubude be-excitation wavelength ngu-745 nm, futhi ubude be-wavelength bungu-815 nm.Isofthiwe ye-Living Image 4.5.5 (PerkinElmer Inc.) isetshenziselwe ukukala umthamo we-fluorescence wemithombo equkethe i-conjugate.
Amandla e-fluorescence kanye nokunqwabelana kwe-conjugate ye-MNP-PLA-EDA-ICG kukalwe ngamagundane emodeli yesimila se-vivo, ngaphandle kokuba khona kanye nokusebenzisa inkambu kazibuthe esizeni sentshisekelo.Amagundane alaliswa izinzwa nge-isoflurane, kwase kuthi u-0.1 mL we-MNP-PLA-EDA-ICG conjugate wajovwa ngomthambo womsila.Amagundane angalashiwe asetshenziswe njengesilawuli esingalungile ukuze kutholwe ingemuva le-fluorescent.Ngemva kokuqondisa i-conjugate ngomthambo, beka isilwane endaweni yokushisa (37°C) ekamelweni le-IVIS Lumina LT series III fluorescence imager (PerkinElmer Inc.) kuyilapho ugcina ukuhogela nge-2% ye-isoflurane anaesthetization.Sebenzisa isihlungi esakhelwe ngaphakathi se-ICG (745–815 nm) ukuze uthole isignali iminithi elingu-1 nemizuzu engu-15 ngemva kokwethulwa kwe-MNP.
Ukuhlola ukuqoqwa kwe-conjugate ku-tumor, indawo ye-peritoneal yesilwane yayimbozwe ngephepha, okwenza kube nokwenzeka ukuqeda i-fluorescence ekhanyayo ehambisana nokuqoqwa kwezinhlayiya esibindi.Ngemva kokutadisha i-biodistribution ye-MNP-PLA-EDA-ICG, izilwane zagunyazwa ngokobuntu ngokudlula ngokweqile kwe-isoflurane anesthesia ngokuhlukaniswa okulandelayo kwezindawo zesimila kanye nokuhlolwa komthamo wemisebe ye-fluorescence.Sebenzisa isofthiwe ye-Living Image 4.5.5 (PerkinElmer Inc.) ukuze ucubungule mathupha ukuhlaziywa kwesignali kusuka endaweni ekhethiwe yentshisekelo.Kuthathwe izilinganiso ezintathu ngesilwane ngasinye (n = 9).
Kulolu cwaningo, asizange sibale ukulayishwa ngempumelelo kwe-ICG kuma-MNPs-ICG.Ukwengeza, asizange siqhathanise ukusebenza kahle kokugcinwa kwe-nanoparticles ngaphansi kwethonya lamagnethi ahlala njalo ezinhlobonhlobo ezahlukene.Ngaphezu kwalokho, asizange sihlole umphumela wesikhathi eside wenkundla kazibuthe ekugcinweni kwama-nanoparticles kumathishu e-tumor.
Ama-nanoparticles ayabusa, ngosayizi ojwayelekile ongu-195.4 nm.Ngaphezu kwalokho, ukumiswa kwakuqukethe ama-agglomerates anosayizi ojwayelekile we-1176.0 nm (Umfanekiso 5A).Kamuva, ingxenye yahlungwa ngesihlungi se-centrifugal.Amandla we-zeta wezinhlayiya yi--15.69 mV (Umfanekiso 5B).
Umfanekiso 5 Izici ezibonakalayo zokumiswa: (A) ukusabalalisa usayizi wezinhlayiyana;(B) ukusatshalaliswa kwezinhlayiyana kumandla we-zeta;(C) Isithombe se-TEM sama-nanoparticles.
Usayizi wezinhlayiyana ngokuyisisekelo ungu-200 nm (Umfanekiso 5C), owenziwe nge-MNP eyodwa enosayizi wama-nm angama-20, kanye negobolondo le-organic elihlanganisiwe le-PLA-EDA-ICG elinobukhulu obuphansi be-electron.Ukwakheka kwama-agglomerate kuzixazululo ezinamanzi kungachazwa yi-modulus ephansi kakhulu yamandla e-electromotive we-nanoparticles ngayinye.
Ngozibuthe unomphela, lapho i-magnetization igxile kuvolumu V, isisho esibalulekile sihlukaniswa sibe izingxenye ezimbili ezibalulekile, okuyivolumu kanye nendawo:
Endabeni yesampula ene-magnetization engashintshi, ukuminyana kwamanje kunguziro.Khona-ke, ukuvezwa kwe-magnetic induction vector kuzothatha ifomu elilandelayo:
Sebenzisa uhlelo lwe-MATLAB (MathWorks, Inc., USA) ukuze uthole izinombolo, inombolo yelayisense yezemfundo ye-ETU “LETI” 40502181.
Njengoba kuboniswe kuMfanekiso 7 Umfanekiso 8 Umfanekiso 9 Umfanekiso-10, inkambu kazibuthe enamandla kakhulu ikhiqizwa uzibuthe oqondiswe ku-axially kusukela ekugcineni kwesilinda.Irediyasi esebenzayo yesenzo ilingana nejiyomethri kazibuthe.Kumazibuthe angama-cylindrical anesilinda ubude bawo bukhulu kunobubanzi bawo, inkambu kazibuthe enamandla kakhulu ibonakala kusiqondiso se-axial-radial (engxenyeni ehambisanayo);ngakho-ke, amasilinda ane-aspect ratio enkulu (ububanzi nobude) i-MNP adsorption iphumelela kakhulu.
Umfanekiso 7 Ingxenye yamandla kazibuthe wokungeniswa Bz eduze kwe-eksisi ye-Oz kazibuthe;ubukhulu obujwayelekile bukazibuthe: umugqa omnyama 0.5×2mm, umugqa oluhlaza okwesibhakabhaka 2×2mm, umugqa oluhlaza 3×2mm, umugqa obomvu 5×2mm.
Umfanekiso 8 Ingxenye ye-magnetic induction Br incike ku-axis kazibuthe Oz;ubukhulu obujwayelekile bukazibuthe: umugqa omnyama 0.5×2mm, umugqa oluhlaza okwesibhakabhaka 2×2mm, umugqa oluhlaza 3×2mm, umugqa obomvu 5×2mm.
Umfanekiso 9 Ukuqina kazibuthe okungeniswayo ingxenye ye-Bz ebangeni r ukusuka eksisi yokugcina kazibuthe (z=0);ubukhulu obujwayelekile bukazibuthe: umugqa omnyama 0.5×2mm, umugqa oluhlaza okwesibhakabhaka 2×2mm, umugqa oluhlaza 3×2mm, umugqa obomvu 5×2mm.
Umfanekiso 10 Ingxenye yokungeniswa kukaMagnetic eduze kwesiqondiso se-radial;usayizi uzibuthe ojwayelekile: umugqa omnyama 0.5×2mm, umugqa oluhlaza okwesibhakabhaka 2×2mm, umugqa oluhlaza 3×2mm, umugqa obomvu 5×2mm.
Amamodeli akhethekile we-hydrodynamic angasetshenziswa ukutadisha indlela yokulethwa kwe-MNP ezicutshini zesimila, ukugxilisa ama-nanoparticles endaweni okuhlosiwe, futhi kunqume ukuziphatha kwe-nanoparticles ngaphansi kwezimo ze-hydrodynamic ohlelweni lokujikeleza kwegazi.Ozibuthe baphakade bangasetshenziswa njengezizibuthe zangaphandle.Uma singakunaki ukusebenzisana kwe-magnetostatic phakathi kwama-nanoparticles futhi singacabangi imodeli yamagnetic fluid, kwanele ukulinganisa ukusebenzisana phakathi kukazibuthe kanye ne-nanoparticle eyodwa ene-dipole-dipole approximation.
Lapho u-m engumzuzu kazibuthe kazibuthe, u-r uyi-radius vector yendawo lapho i-nanoparticle ikhona, futhi u-k uyisici sesistimu.Ekulinganisweni kwe-dipole, inkambu yamagnetic inokucushwa okufanayo (Umfanekiso we-11).
Endaweni efanayo kazibuthe, ama-nanoparticles azungeza kuphela emigqeni yamandla.Endaweni kazibuthe engalingani, amandla asebenza kuyo:
Iphi i-derivative yesikhombisi-ndlela esinikeziwe l.Ngaphezu kwalokho, amandla adonsela ama-nanoparticles ezindaweni ezingalingani kakhulu zensimu, okungukuthi, ukugoba nokuqina kwemigqa yamandla akhuphuka.
Ngakho-ke, kuyinto efiselekayo ukusebenzisa uzibuthe oqinile ngokwanele (noma iketango lamagnetic) nge-axial anisotropy esobala endaweni lapho izinhlayiya zitholakala khona.
Ithebula 1 libonisa amandla kazibuthe owodwa njengomthombo wenkundla kazibuthe owanele wokuthwebula nokugcina i-MNP kumbhede wemithambo wendawo yohlelo lokusebenza.