I-Javascript okwamanje ikhutshaziwe kusiphequluli sakho. Uma i-javascript ikhutshaziwe, eminye imisebenzi yale webhusayithi ngeke isebenze.
Bhalisa imininingwane yakho ethile kanye nemithi ethile oyithandayo, futhi sizofanisa ulwazi olunikezayo nezihloko eziku-database yethu ebanzi bese sikuthumelela ikhophi ye-PDF nge-imeyili ngesikhathi esifanele.
Lawula ukuhamba kwama-nanoparticles e-magnetic iron oxide ukuze kutholakale ama-cytostatics aqondiwe
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 u-Alexey Petukhov,1,3 uVladimir Mishanin,1 uAndrey Gorshkov,4 uEkaterina Podyacheva,1 uKamil Gareev,2 u-Alexei Bagrov,5 u-Oleg Demidov6,71 i-Almazov National Medical Research Center yoMnyango Wezempilo we-Russian Federation, eSt. Petersburg, 197341, i-Russian Federation; 2 i-St. Petersburg Electrotechnical University “LETI”, eSt. Petersburg, 197376, i-Russian Federation; 3 Isikhungo Sezokwelapha Eziqondene Nakho, i-Almazov State Medical Research Center, i-Ministry of Health ye-Russian Federation, eSt. Petersburg, 197341, i-Russian Federation; 4 i-FSBI “Influenza Research Institute eqanjwe nge-AA Smorodintsev” i-Ministry of Health ye-Russian Federation, eSt. Petersburg, i-Russian Federation; 5 i-Sechenov Institute of Evolutionary Physiology and Biochemistry, i-Russian Academy of Sciences, eSt. Petersburg, i-Russian Federation; 6 I-RAS Institute of Cytology, eSt. Petersburg, 194064, eRussian Federation; 7INSERM U1231, i-Faculty of Medicine and Pharmacy, eBourgogne-Franche Comté University of Dijon, eFrance Ukuxhumana: Yana ToropovaAlmazov National Medical Research Centre, Ministry of Health of the Russian Federation, Saint-Petersburg, 197341, Russian Federation Ucingo +7 981 95264800 4997069 I-imeyili [email protected] Ingemuva: Indlela ethembisayo yenkinga yobuthi be-cytostatic ukusetshenziswa kwama-magnetic nanoparticles (MNP) ekulethweni kwemithi okuqondiswe kuyo. Inhloso: Ukusebenzisa izibalo ukuthola izici ezinhle kakhulu zensimu yamagnetic elawula ama-MNPs emzimbeni, kanye nokuhlola ukusebenza kahle kokulethwa kwe-magnetron kwama-MNPs ezimila zegundane ngaphakathi kwe-vitro kanye nase-vivo. Kusetshenziswa (i-MNPs-ICG). Izifundo zokukhanya kwe-in vivo zenziwa emagundwini esimila, anensimu yamagnetic nangaphandle kwayo endaweni ethandwayo. Lezi zifundo zenziwe esikhaleni se-hydrodynamic esakhiwe yi-Institute of Experimental Medicine ye-Almazov State Medical Research Center yoMnyango Wezempilo waseRussia. Umphumela: Ukusetshenziswa kwama-neodymium magnets kwakhuthaza ukuqongelela okukhethekile kwe-MNP. Umzuzu owodwa ngemuva kokunikezwa kwe-MNPs-ICG kumagundane aphethe isimila, i-MNPs-ICG iqongelela kakhulu esibindini. Uma kungekho futhi kukhona insimu yamagnetic, lokhu kubonisa indlela yayo yokusebenza. Nakuba ukwanda kwe-fluorescence esimila kwabonakala lapho kukhona insimu yamagnetic, ukuqina kwe-fluorescence esibindini sesilwane akuzange kushintshe ngokuhamba kwesikhathi. Isiphetho: Lolu hlobo lwe-MNP, oluhlanganiswe namandla ensimu yamagnetic abaliwe, lungaba yisisekelo sokuthuthukiswa kokulethwa kwemithi ye-cytostatic elawulwa ngomagnetic ezicutshini zesimila. Amagama angukhiye: ukuhlaziywa kwe-fluorescence, i-indocyanine, ama-nanoparticles e-iron oxide, ukulethwa kwe-magnetron kwe-cytostatics, ukuqondiswa kwesimila
Izifo zesimila zingenye yezimbangela ezinkulu zokufa emhlabeni jikelele. Ngesikhathi esifanayo, ukuguquguquka kokwanda kokugula nokufa kwezifo zesimila kusekhona. 1 I-chemotherapy esetshenziswa namuhla isengenye yezindlela eziyinhloko zokwelapha izimila ezahlukene. Ngesikhathi esifanayo, ukuthuthukiswa kwezindlela zokunciphisa ubuthi be-cytostatics kusabalulekile. Indlela ethembisayo yokuxazulula inkinga yayo yobuthi ukusebenzisa abathwali be-nano-scale ukuqondisa izindlela zokulethwa kwemithi, ezinganikeza ukuqongelela kwemithi endaweni ethile ezicutshini zesimila ngaphandle kokwandisa ukuqongelela kwayo ezithweni nasezicutshini ezinempilo. 2 Le ndlela yenza kube nokwenzeka ukuthuthukisa ukusebenza kahle kanye nokuqondiswa kwemithi ye-chemotherapy ezicutshini zesimila, ngenkathi kunciphisa ubuthi bayo be-systemic.
Phakathi kwama-nanoparticle ahlukahlukene acatshangelwa ukulethwa okuqondiwe kwama-cytostatic agents, ama-magnetic nanoparticles (MNPs) athakazelisa kakhulu ngenxa yezakhiwo zawo ezihlukile zamakhemikhali, zebhayoloji, kanye nezama-magnetic, okuqinisekisa ukuguquguquka kwawo. Ngakho-ke, ama-magnetic nanoparticles angasetshenziswa njengohlelo lokushisa ukwelapha izimila ezine-hyperthermia (magnetic hyperthermia). Angasetshenziswa futhi njengezinto zokuxilonga (magnetic resonance diagnosis). 3-5 Ukusebenzisa lezi zici, kuhlanganiswe nokwenzeka kokuqongelela kwe-MNP endaweni ethile, ngokusebenzisa insimu yamagnetic yangaphandle, ukulethwa kwemithi eqondiwe kuvula ukudalwa kohlelo lwe-magnetron olunemisebenzi eminingi ukuze kuqondiswe ama-cytostatics endaweni yesimila Amathemba. Uhlelo olunjalo luzofaka i-MNP kanye nama-magnetic field ukulawula ukunyakaza kwawo emzimbeni. Kulokhu, kokubili ama-magnetic field angaphandle kanye nokufakelwa kwama-magnetic okubekwe endaweni yomzimba equkethe isimila kungasetshenziswa njengomthombo wensimu yamagnetic. 6 Indlela yokuqala inezinkinga ezinkulu, okuhlanganisa isidingo sokusebenzisa imishini ekhethekile yokuqondisa izidakamizwa kuma-magnetic kanye nesidingo sokuqeqesha abasebenzi ukwenza ukuhlinzwa. Ngaphezu kwalokho, le ndlela inqunyelwe yizindleko eziphakeme futhi ifaneleka kuphela kuma-tumors "angaphandle" aseduze nobuso bomzimba. Enye indlela yokusebenzisa ama-implants kazibuthe yandisa ububanzi bokusetshenziswa kwalobu buchwepheshe, okwenza kube lula ukusetshenziswa kwawo kuma-tumors atholakala ezingxenyeni ezahlukene zomzimba. Ama-magnets ngamanye kanye nama-magnets ahlanganiswe ne-intraluminal stent angasetshenziswa njenge-implants yokulimala kwama-tumour ezithweni ezingenalutho ukuqinisekisa ukuthi ayakwazi ukuqina. Kodwa-ke, ngokocwaningo lwethu olungakashicilelwa, lawa awanele ama-magnetic ukuqinisekisa ukugcinwa kwe-MNP egazini.
Ukusebenza kahle kokulethwa kwemithi ye-magnetron kuncike ezintweni eziningi: izici zesithwali sikamazibuthe uqobo, kanye nezici zomthombo wensimu kazibuthe (kufaka phakathi amapharamitha ejiyometri wamagnethi ahlala njalo kanye namandla ensimu kazibuthe ayikhiqizayo). Ukuthuthukiswa kobuchwepheshe bokulethwa kwe-magnetic cell inhibitor obuqondiswa amandla kazibuthe obuphumelelayo kufanele kuhilele ukuthuthukiswa kwezithwali zemithi ze-magnetic nanoscale ezifanele, ukuhlola ukuphepha kwazo, kanye nokuthuthukisa inqubo yokubona evumela ukulandelela ukunyakaza kwazo emzimbeni.
Kulolu cwaningo, sibale ngokwezibalo izici zensimu yamagnetic ezifanele ukulawula isithwali semithi ye-magnetic nano-scale emzimbeni. Amathuba okugcina i-MNP odongeni lwemithambo yegazi ngaphansi kwethonya lensimu yamagnetic esetshenzisiwe enalezi zici zokubala nawo afundwe emithanjeni yegazi yamagundane ahlukanisiwe. Ngaphezu kwalokho, sakha ama-conjugates e-MNP kanye nama-fluorescent agents futhi sakha inqubo yokubonakala kwawo emzimbeni. Ngaphansi kwezimo ze-in vivo, emagundwini emodeli yesimila, ukusebenza kahle kokuqongelela kwe-MNPs ezicutshini zesimila lapho kunikezwa ngendlela ehlelekile ngaphansi kwethonya lensimu yamagnetic kwafundwa.
Esifundweni se-in vitro, sisebenzise i-MNP ebhekisela kuyo, kanti esifundweni se-in vivo, sisebenzise i-MNP embozwe nge-lactic acid polyester (i-polylactic acid, i-PLA) equkethe i-fluorescent agent (indolecyanine; i-ICG). I-MNP-ICG ifakiwe kulesi sihloko. Esimweni, sebenzisa (i-MNP-PLA-EDA-ICG).
Izakhiwo zokwenziwa kanye nezakhiwo zomzimba nezamakhemikhali ze-MNP zichazwe ngokuningiliziwe kwenye indawo.
Ukuze kuhlanganiswe ama-MNP-ICG, kwaqala kwakhiqizwa ama-conjugates e-PLA-ICG. Kwasetshenziswa ingxube ye-racemic ye-PLA-D ne-PLA-L enesisindo sama-molecule esingu-60 kDa.
Njengoba i-PLA kanye ne-ICG zombili ziyi-asidi, ukuze kuhlanganiswe ama-PLA-ICG conjugates, kudingeka kuqala kuhlanganiswe i-amino-terminated spacer ku-PLA, esiza i-ICG chemisorb ku-spacer. I-spacer yenziwe 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 yenziwe kanje. Engeza i-EDA eningi ka-20-fold molar kanye ne-EDAC eningi ka-20-fold molar kuya ku-2 mL yesisombululo se-PLA chloroform esingu-0.1 g/mL. Ukuhlanganiswa kwenziwe nge-15 mL polypropylene test tube ku-shaker ngesivinini semizuzu engu-300-1 amahora ama-2. Uhlelo lokuhlanganisa luboniswe ku-Figure 1. Phinda ukuhlanganiswa ngama-reagents eningi ka-200-fold ukuze uthuthukise uhlelo lokuhlanganisa.
Ekupheleni kokwenziwa, isixazululo safakwa ku-centrifuge ngesivinini esingu-3000 min-1 imizuzu emi-5 ukuze kususwe ama-precipitated polyethylene derivatives amaningi. Ngemuva kwalokho, i-2 mL yesisombululo se-ICG esingu-0.5 mg/mL ku-dimethyl sulfoxide (DMSO) yanezelwa kusisombululo esingu-2 mL. I-agitator iqiniswa ngesivinini sokuxubha esingu-300 min-1 amahora ama-2. Umdwebo we-schematic we-conjugate etholiwe uboniswe ku-Figure 2.
Ku-200 mg ye-MNP, sengeze i-4 mL PLA-EDA-ICG conjugate. Sebenzisa i-LS-220 shaker (LOIP, Russia) ukuze uvuselele i-suspension imizuzu engama-30 ngemvamisa yemizuzu engama-300-1. Ngemuva kwalokho, yagezwa nge-isopropanol kathathu futhi yahlukaniswa nge-magnetic. Sebenzisa i-UZD-2 Ultrasonic Disperser (FSUE NII TVCH, Russia) ukuze wengeze i-IPA ku-suspension imizuzu emi-5-10 ngaphansi kwesenzo se-ultrasonic esiqhubekayo. Ngemva kokugeza kwesithathu kwe-IPA, i-precipitate yagezwa ngamanzi acwengekile futhi yaphinde yaxhonywa ku-physiological saline ku-concentration engu-2 mg/mL.
Imishini ye-ZetaSizer Ultra (i-Malvern Instruments, e-UK) yasetshenziswa ukutadisha ukusatshalaliswa kosayizi we-MNP etholwe kusisombululo samanzi. I-transmission electron microscope (TEM) ene-JEM-1400 STEM field emission cathode (i-JEOL, eJapane) yasetshenziswa ukutadisha ukuma nobukhulu be-MNP.
Kulesi sifundo, sisebenzisa omaginethi abaphakade abayisilinda (ibanga le-N35; abane-nickel protective coating) kanye nosayizi abalandelayo abajwayelekile (ubude be-axis ende × ububanzi besilinda): 0.5×2 mm, 2×2 mm, 3×2 mm kanye no-5×2 mm.
Ucwaningo lwe-in vitro lokuthuthwa kwe-MNP ohlelweni lwemodeli lwenziwe ku-scaffold ye-hydrodynamic eyakhiwe yi-Institute of Experimental Medicine ye-Almazov State Medical Research Center yoMnyango Wezempilo waseRussia. Umthamo woketshezi olujikelezayo (amanzi acwengekile noma isixazululo se-Krebs-Henseleit) ungama-225 mL. Amamagnethi aqinile ane-axial asetshenziswa njengamamagnethi ahlala njalo. Beka imagnethi ku-holder 1.5 mm kude nodonga lwangaphakathi lwe-tube yengilazi ephakathi, kanti ukuphela kwayo kubheke ohlangothini lwe-tube (okuqondile). Izinga lokugeleza koketshezi ku-loop evaliwe lingu-60 L/h (okuhambisana nejubane eliqondile elingu-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 elifakwe ensimini yamagnetic linqunywa yi-spectrophotometry kusukela ekugxilweni kwensimbi kuketshezi olujikelezayo ngemuva kokuhlolwa.
Ngaphezu kwalokho, kwenziwe izifundo zokuhlola etafuleni elithuthukisiwe le-fluid mechanics ukuze kutholakale ukugeleza kwegazi okuhlobene. Izingxenye eziyinhloko zokusekelwa kwe-hydrodynamic ziboniswe kuMfanekiso 3. Izingxenye eziyinhloko ze-hydrodynamic stent ziyi-loop evaliwe elingisa ingxenye evundlile yesistimu yemithambo yegazi eyisibonelo kanye nethangi lokugcina. Ukuhamba koketshezi lwemodeli eceleni kwe-contour ye-module yemithambo yegazi kunikezwa yiphampu ye-peristaltic. Ngesikhathi sokuhlola, gcina ukuhwamuka kanye nobubanzi bokushisa obudingekayo, futhi uqaphe amapharamitha esistimu (izinga lokushisa, ingcindezi, izinga lokugeleza koketshezi, kanye nenani le-pH).
Umfanekiso 3 Umdwebo webhulokhi wokusetha okusetshenziselwa ukutadisha ukuvuleka kodonga lwe-carotid artery. Ithangi lokugcina eli-1, iphampu ye-peristaltic engu-2, indlela engu-3 yokufaka ukumiswa okuqukethe i-MNP ku-loop, imitha yokugeleza engu-4, inzwa yokucindezela engu-5 ku-loop, i-heat exchanger engu-6, igumbi elingu-7 elinesitsha, 8-umthombo wensimu yamagnetic, 9-ibhaluni elinama-hydrocarbon.
Ikamelo eliqukethe isitsha liqukethe izitsha ezintathu: isitsha esikhulu sangaphandle kanye nezitsha ezimbili ezincane, lapho izingalo zesekethe eliphakathi zidlula khona. I-cannula ifakwa esitsheni esincane, isitsha siboshwe ngentambo esitsheni esincane, kanti isihloko se-cannula siboshwe ngokuqinile ngentambo encane. Isikhala esiphakathi kwesitsha esikhulu nesitsha esincane sigcwele amanzi acwengekile, futhi izinga lokushisa lihlala lingaguquki ngenxa yokuxhumeka ku-heat exchanger. Isikhala esitsheni esincane sigcwele isixazululo se-Krebs-Henseleit ukuze kugcinwe ukusebenza kwamaseli emithambo yegazi. Ithangi liphinde ligcwaliswe ngesisombululo se-Krebs-Henseleit. Uhlelo lokuhlinzeka ngegesi (ikhabhoni) lusetshenziselwa ukufudumeza isixazululo esitsheni esincane esisethangini lokugcina kanye negumbi eliqukethe isitsha (Isithombe 4).
Isithombe 4 Igumbi lapho kufakwa khona isitsha. 1-I-Cannula yokwehlisa imithambo yegazi, 2-Igumbi langaphandle, 3-Igumbi elincane. Umcibisholo ubonisa indlela uketshezi oluyimodeli oluqondiswa ngayo.
Ukuze kutholakale inkomba yokuvuleka kodonga lwemithambo yegazi, kwasetshenziswa umthambo we-rat carotid.
Ukufakwa kokumiswa kwe-MNP (0.5mL) ohlelweni kunezici ezilandelayo: ivolumu yangaphakathi iyonke yethangi kanye nepayipi lokuxhuma ku-loop ingu-20mL, kanti ivolumu yangaphakathi yekamelo ngalinye ingu-120mL. Umthombo wangaphandle wensimu yamagnetic uyimagnethi ehlala njalo enosayizi ojwayelekile ongu-2×3 mm. Ifakwe ngaphezu kwelinye lamakamelo amancane, 1 cm ukusuka esitsheni, kanti umkhawulo owodwa ubheke odongeni lwesitsha. Izinga lokushisa ligcinwa ku-37°C. Amandla epompo ye-roller asethwe ku-50%, okuhambisana nesivinini esingu-17 cm/s. Njengokulawula, amasampula athathwe esitokisini esingenamagnethi ahlala njalo.
Ihora elilodwa ngemva kokuphathwa kwe-MNP ethile, kwathathwa isampula yoketshezi ekamelweni. I-particle concentration yalinganiswa nge-spectrophotometer kusetshenziswa i-Unico 2802S UV-Vis spectrophotometer (United Products & Instruments, USA). Uma kucatshangelwa i-absorption spectrum ye-MNP suspension, ukulinganisa kwenziwa ku-450 nm.
Ngokweziqondiso ze-Rus-LASA-FELASA, zonke izilwane zikhuliswa futhi zikhuliswe ezindaweni ezithile ezingenazo izifo. Lolu cwaningo luhambisana nayo yonke imithetho yokuziphatha efanele yokuhlolwa kwezilwane nocwaningo, futhi luthole imvume yokuziphatha evela e-Almazov National Medical Research Center (IACUC). Izilwane zaziphuza amanzi ngokushesha futhi zondliwa njalo.
Ucwaningo lwenziwe kumagundane ayi-10 abesilisa angenawo amasosha omzimba angenawo amasosha omzimba aneminyaka engu-12 ubudala (NOD.Cg-Prkdcscid Il2rgtm1Wjl/Szj, Jackson Laboratory, USA) 10, anesisindo esingu-22 g ± 10%. Njengoba ukuzivikela kwamagundane angenawo amasosha omzimba kucindezelwe, amagundane angenawo amasosha omzimba alolu hlobo avumela ukufakelwa kwamangqamuzana nezicubu zabantu ngaphandle kokwenqatshwa kokufakelwa. Amagundane avela ezindlini ezahlukene abelwa ngokungahleliwe eqenjini lokuhlola, futhi ahlanganiswa ndawonye noma abekwe ngokuhlelekile embhedeni wamanye amaqembu ukuqinisekisa ukuvezwa okufanayo kwi-microbiota evamile.
Umugqa weseli lomdlavuza womuntu i-HeLa usetshenziselwa ukusungula imodeli ye-xenograft. Amaseli akhuliswe ku-DMEM equkethe i-glutamine (i-PanEco, eRussia), engezwe nge-serum ye-fetal bovine engu-10% (i-Hyclone, e-USA), i-penicillin engu-100 CFU/mL, kanye ne-streptomycin engu-100 μg/mL. Umugqa weseli wanikezwa ngomusa yi-Gene Expression Regulation Laboratory ye-Institute of Cell Research ye-Russian Academy of Sciences. Ngaphambi kokujova, amaseli e-HeLa asuswa epulasitikini lokukhuliswa ngesisombululo se-trypsin:Versene esingu-1:1 (i-Biolot, eRussia). Ngemva kokugezwa, amaseli alengiswe endaweni ephakathi nendawo kuze kube yilapho kuqongelelwa amaseli angu-5×106 ku-200 μL, futhi axutshwe ne-basement membrane matrix (i-LDEV-FREE, MATRIGEL® CORNING®) (1:1, eqhweni). Ukumiswa kweseli okulungiselelwe kwajovwa ngaphansi kwesikhumba sethanga legundane. Sebenzisa ama-caliper kagesi ukuqapha ukukhula kwesimila njalo ezinsukwini ezi-3.
Lapho isimila sifinyelela ku-500 mm3, kwafakwa i-magnet ehlala njalo ezicutshini zemisipha yesilwane esihlolwayo eduze kwesimila. Eqenjini lokuhlola (i-MNPs-ICG + i-tumor-M), i-0.1 mL yokumiswa kwe-MNP yajovwa futhi yavezwa ensimini yamagnetic. Izilwane eziphelele ezingalashwanga zasetshenziswa njengezilawuli (ingemuva). Ngaphezu kwalokho, kwasetshenziswa izilwane ezijovwe nge-0.1 mL ye-MNP kodwa ezingafakwanga omamagnethi (i-MNPs-ICG + i-tumor-BM).
Ukuboniswa kwe-fluorescence kwamasampula e-in vivo kanye ne-in vitro kwenziwe ku-IVIS Lumina LT series III bioimager (PerkinElmer Inc., USA). Ukuze kuboniswe nge-in vitro, ivolumu engu-1 mL ye-synthetic PLA-EDA-ICG kanye ne-MNP-PLA-EDA-ICG conjugate yengezwe emigodini yamapuleti. Uma kucatshangelwa izici ze-fluorescence zedayi ye-ICG, kukhethwa isihlungi esingcono kakhulu esisetshenziselwa ukunquma ukuqina okukhanyayo kwesampula: ubude be-excitation obukhulu bungu-745 nm, kanti ubude be-emission bungu-815 nm. Isofthiwe ye-Living Image 4.5.5 (PerkinElmer Inc.) yasetshenziswa ukulinganisa ngobuningi ukuqina kwe-fluorescence yemigodi equkethe i-conjugate.
Ukuqina kwe-fluorescence kanye nokuqongelela kwe-conjugate ye-MNP-PLA-EDA-ICG kwalinganiswa kumagundane emodeli yesimila esiphilayo, ngaphandle kokuba khona kanye nokusetshenziswa kwensimu yamagnetic endaweni ethandwayo. Amagundane ahlanzwa nge-isoflurane, kwabe sekufakwa i-0.1 mL ye-conjugate ye-MNP-PLA-EDA-ICG ngomthambo womsila. Amagundane angelashwanga asetshenziswa njengokulawula okungekuhle ukuthola isizinda se-fluorescent. Ngemva kokufaka i-conjugate ngemithambo yegazi, beka isilwane esigabeni sokushisa (37°C) ekamelweni le-IVIS Lumina LT series III fluorescence imager (PerkinElmer Inc.) ngenkathi uqhubeka nokuphefumula nge-2% isoflurane anaesthetization. Sebenzisa isihlungi esakhelwe ngaphakathi se-ICG (745–815 nm) ukuthola isignali umzuzu owodwa nemizuzu eyi-15 ngemuva kokufakwa kwe-MNP.
Ukuze kuhlolwe ukuqongelela kwe-conjugate esimilanjeni, indawo ye-peritoneal yesilwane yambozwa ngephepha, okwenza kwaba nokwenzeka ukuqeda ukukhanya okukhanyayo okuhlobene nokuqongelela kwezinhlayiya esibindini. Ngemva kokufunda ukusatshalaliswa kwe-biodistribution ye-MNP-PLA-EDA-ICG, izilwane zabulawa ngobuntu ngokudla ngokweqile i-isoflurane anesthesia ukuze kuhlukaniswe izindawo zesimila ngokulandelayo kanye nokuhlolwa kobuningi bemisebe ye-fluorescence. Sebenzisa isofthiwe ye-Living Image 4.5.5 (PerkinElmer Inc.) ukucubungula ngesandla ukuhlaziywa kwesignali kusuka esifundeni esikhethiwe esithandwayo. Kwathathwa izilinganiso ezintathu zesilwane ngasinye (n = 9).
Kulolu cwaningo, asizange silinganisele ukulayisha okuphumelelayo kwe-ICG ku-MNPs-ICG. Ngaphezu kwalokho, asizange siqhathanise ukusebenza kahle kokugcinwa kwama-nanoparticles ngaphansi kwethonya lama-magnets ahlala njalo anezimo ezahlukene. Ngaphezu kwalokho, asizange sihlole umphumela wesikhathi eside wensimu yamagnetic ekugcinweni kwama-nanoparticles ezicutshini zesimila.
Ama-nanoparticles ayabusa, ngobukhulu obumaphakathi obungu-195.4 nm. Ngaphezu kwalokho, ukumiswa kwakuqukethe ama-agglomerate anobukhulu obumaphakathi obungu-1176.0 nm (Isithombe 5A). Ngemva kwalokho, ingxenye yahlungwa ngesihlungi se-centrifugal. Amandla e-zeta ezinhlayiya angu--15.69 mV (Isithombe 5B).
Umfanekiso 5 Izakhiwo ezibonakalayo zokumiswa: (A) ukusatshalaliswa kosayizi wezinhlayiya; (B) ukusatshalaliswa kwezinhlayiya ku-zeta potential; (C) Isithombe se-TEM sezinhlayiya ezincane.
Usayizi wezinhlayiya ngokuyisisekelo ungama-200 nm (Isithombe 5C), esakhiwe yi-MNP eyodwa enobukhulu obungama-20 nm, kanye negobolondo le-PLA-EDA-ICG elihlanganisiwe elinobuningi obuphansi be-electron. Ukwakheka kwama-agglomerate ezixazululweni zamanzi kungachazwa yi-modulus ephansi kakhulu yamandla e-electromotive e-nanoparticles ngayinye.
Kuma-magnet ahlala njalo, lapho i-magnetization igxile ku-volume V, ukubonakaliswa kwe-integral kuhlukaniswe ngama-integral amabili, okungukuthi i-volume kanye nobuso:
Uma kwenzeka isampula ene-magnetization engaguquki, ubuningi bamanje bungu-zero. Ngemuva kwalokho, ukubonakaliswa kwe-vector ye-magnetic induction kuzothatha isimo esilandelayo:
Sebenzisa uhlelo lwe-MATLAB (MathWorks, Inc., USA) ekubaleni ngezinombolo, inombolo yelayisensi yezemfundo ye-ETU “LETI” engu-40502181.
Njengoba kuboniswe kuMfanekiso 7 Umfanekiso 8 Umfanekiso 9 Umfanekiso-10, insimu yamagnetic enamandla kakhulu ikhiqizwa yi-magnet eqondiswe ku-axial kusukela ekugcineni kwesilinda. Irediyasi yesenzo ephumelelayo ilingana ne-geometry yamagnet. Kumagnethi asilinda anesilinda ubude bawo bukhulu kunobubanzi bawo, insimu yamagnetic enamandla kakhulu ibonwa ohlangothini lwe-axial-radial (lwengxenye ehambisanayo); ngakho-ke, amasilinda amabili anesilinganiso esikhulu (ububanzi nobude) i-MNP adsorption iyona ephumelela kakhulu.
Isithombe 7 Ingxenye yokuqina kokungeniswa kwamagnetic Bz eceleni kwe-Oz axis yamagnet; usayizi ojwayelekile wamagnet: umugqa omnyama ongu-0.5×2mm, umugqa oluhlaza okwesibhakabhaka ongu-2×2mm, umugqa oluhlaza ongu-3×2mm, umugqa obomvu ongu-5×2mm.
Umfanekiso 8 Ingxenye yokungenisa amandla kagesi i-Br iqonde ngqo ku-axis yemagnethi i-Oz; usayizi ojwayelekile wamagnethi: umugqa omnyama ongu-0.5×2mm, umugqa oluhlaza okwesibhakabhaka ongu-2×2mm, umugqa oluhlaza ongu-3×2mm, umugqa obomvu ongu-5×2mm.
Umfanekiso 9 Ingxenye ye-Bz yokufakwa kwamandla kagesi ebangeni elingu-r ukusuka ku-axis yokugcina kamazibuthe (z=0); usayizi ojwayelekile kamazibuthe: umugqa omnyama ongu-0.5×2mm, umugqa oluhlaza okwesibhakabhaka ongu-2×2mm, umugqa oluhlaza okwesibhakabhaka ongu-3×2mm, umugqa obomvu ongu-5×2mm.
Umfanekiso 10 Ingxenye yokungeniswa kwe-magnetic eceleni kwesiqondiso se-radial; usayizi ojwayelekile we-magnet: umugqa omnyama ongu-0.5×2mm, umugqa oluhlaza okwesibhakabhaka ongu-2×2mm, umugqa oluhlaza ongu-3×2mm, umugqa obomvu ongu-5×2mm.
Amamodeli akhethekile e-hydrodynamic angasetshenziswa ukutadisha indlela yokulethwa kwe-MNP ezicutshini zesimila, ukugxila kwama-nanoparticles endaweni eqondiwe, nokunquma ukuziphatha kwama-nanoparticles ngaphansi kwezimo ze-hydrodynamic ohlelweni lokujikeleza kwegazi. Ama-magnets ahlala njalo angasetshenziswa njengezinkundla zamagnetic zangaphandle. Uma singayinaki i-magnetostatic interactions phakathi kwama-nanoparticles futhi singacabangi ngemodeli ye-magnetic fluid, kwanele ukulinganisa i-interactions phakathi kwe-magnet kanye ne-nanoparticle eyodwa ene-dipole-dipole approximation.
Lapho u-m eyisikhathi esinobuthi semagnethi, u-r uyivektha yerediyasi yephuzu lapho kutholakala khona i-nanoparticle, kanti u-k uyisici sesistimu. Ku-poproximation ye-dipole, insimu yemagnethi inokulungiswa okufanayo (Isithombe 11).
Ensimini yamagnetic efanayo, ama-nanoparticles ajikeleza kuphela emigqeni yamandla. Ensimini yamagnetic engalingani, amandla asebenza kuwo:
Ikuphi i-derivative yesiqondiso esinikeziwe l. Ngaphezu kwalokho, amandla adonsela ama-nanoparticles ezindaweni ezingalingani kakhulu zensimu, okungukuthi, ukugoba kanye nobuningi bemigqa yamandla kuyanda.
Ngakho-ke, kuyafiseleka ukusebenzisa i-magnet enamandla ngokwanele (noma i-magnet chain) ene-anisotropy ecacile ye-axial endaweni lapho izinhlayiya zitholakala khona.
Ithebula 1 libonisa ikhono likamagnet elilodwa njengomthombo wensimu yamagnetic owanele wokubamba nokugcina i-MNP embhedeni wemithambo yensimu yesicelo.