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Laola motsamao oa magnetic iron oxide nanoparticles bakeng sa phano e lebisitsoeng ea cytostatics
Mongoli Toropova 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 Demidov6,71Almazov National Setsi sa Lipatlisiso sa Lekala la Bophelo la Russia Federation, St. Petersburg, 197341, Russia Federation;2 St. Petersburg Electrotechnical University "LETI", St. Petersburg, 197376, Russia Federation;3 Setsi sa Meriana ea Boipheliso, Setsi sa Lipatlisiso sa Bongaka sa Almazov State, Lekala la Bophelo la Russia Federation, St. Petersburg, 197341, Russia Federation;4FSBI "Influenza Research Institute e reheletsoeng ka AA Smorodintsev" Lekala la Bophelo la Russia Federation, St. Petersburg, Russia Federation;5 Sechenov Institute of Evolutionary Physiology le Biochemistry, Russian Academy of Sciences, St. Petersburg, Russia Federation;6 RAS Institute of Cytology, St. Petersburg, 194064, Russia Federation;7INSERM U1231, Faculty of Medicine le Pharmacy, Bourgogne-Franche Comté University of Dijon, Fora Puisano: Yana ToropovaAlmazov National Medical Research Center, Lekala la Bophelo la Russia Federation, Saint-Petersburg, 197341, Russia Federation Tel +7 981 952694800 952694800 [imeile e sirelelitsoeng] Background: Tsela e tšepisang bothateng ba cytostatic toxicity ke tšebeliso ea magnetic nanoparticles (MNP) bakeng sa ho fana ka lithethefatsi tse lebisitsoeng.Sepheo: Ho sebelisa lipalo ho fumana litšobotsi tse ntle ka ho fetisisa tsa matla a khoheli a laolang MNPs ka har'a vivo, le ho lekola bokhoni ba ho fana ka magnetron ea MNP ho lihlahala tsa mouse in vitro le vivo.(MNPs-ICG) e sebelisoa.Lithuto tse matla tsa in vivo luminescence li entsoe ho litoeba tsa hlahala, ka ntle le matla a khoheli sebakeng sa thahasello.Lithuto tsena li ile tsa etsoa ka scaffold ea hydrodynamic e entsoeng ke Institute of Experimental Medicine ea Almazov State Medical Research Center ea Lekala la Bophelo la Russia.Sephetho: Tšebeliso ea makenete a neodymium e khothalelitse ho bokellana ha MNP.Motsotso o le mong ka mor'a tsamaiso ea MNPs-ICG ho litoeba tse nang le tumor, MNPs-ICG haholo-holo e bokella sebeteng.Ha ho le sieo le boteng ba matla a khoheli, sena se bontša tsela ea eona ea metabolic.Le hoja ho eketseha ha fluorescence ka hlahala ho ile ha hlokomeloa ka pel'a matla a khoheli, matla a fluorescence sebeteng sa phoofolo ha aa ka a fetoha ka mor'a nako.Qetello: Mofuta ona oa MNP, o kopantsoeng le matla a matla a khoheli a baloang, e ka ba motheo oa nts'etsopele ea phano e laoloang ke matla ea lithethefatsi tsa cytostatic ho lisele tsa hlahala.Mantsoe a bohlokoa: tlhahlobo ea fluorescence, indocyanine, iron oxide nanoparticles, magnetron delivery of cytostatics, tumor targeting
Mafu a hlahala ke a mang a lisosa tse ka sehloohong tsa lefu lefatšeng ka bophara.Ka nako e ts'oanang, matla a ho eketseha ha mafu le ho shoa ha mafu a hlahala a ntse a le teng.1 Kalafo ea lik'hemik'hale e sebelisoang kajeno e ntse e le e 'ngoe ea liphekolo tsa mantlha bakeng sa lihlahala tse fapaneng.Ka nako e ts'oanang, nts'etsopele ea mekhoa ea ho fokotsa chefo ea systemic ea cytostatics e ntse e sebetsa.Mokhoa o ts'episang oa ho rarolla bothata ba chefo ke ho sebelisa li-nano-scale carriers ho lebisa mekhoa ea phepelo ea lithethefatsi, e ka fanang ka pokello ea lehae ea lithethefatsi ka har'a lisele tsa tumor ntle le ho eketsa ho bokellana ha tsona lithong le liseleng tse phetseng hantle.ho tsepamisa maikutlo.2 Mokhoa ona o etsa hore ho khonehe ho ntlafatsa ts'ebetso le sepheo sa lithethefatsi tsa chemotherapeutic ho lisele tsa tumor, ha li ntse li fokotsa chefo ea tsona.
Har'a li-nanoparticles tse fapaneng tse nkiloeng bakeng sa ho fana ka li-cytostatic agents, magnetic nanoparticles (MNPs) li thahasella ka ho khetheha ka lebaka la lik'hemik'hale tsa tsona tse ikhethang, tsa likokoana-hloko le tsa matla a khoheli, tse netefatsang hore li na le mekhoa e mengata.Ka hona, li-magnetic nanoparticles li ka sebelisoa e le mokhoa oa ho futhumatsa ho phekola lihlahala tse nang le hyperthermia (magnetic hyperthermia).Li ka boela tsa sebelisoa e le lisebelisoa tsa ho hlahloba (magnetic resonance diagnosis).3-5 Ho sebelisa litšoaneleho tsena, ho kopantsoe le monyetla oa ho bokella MNP sebakeng se itseng, ka tšebeliso ea matla a khoheli a kantle, ho fana ka litokisetso tsa meriana tse lebisitsoeng ho bula ho thehoa ha tsamaiso e mengata ea magnetron ho lebisa tlhokomelo ea cytostatics sebakeng sa hlahala. Litebello.Tsamaiso e joalo e ka kenyelletsa MNP le matla a khoheli ho laola motsamao oa tsona 'meleng.Tabeng ena, matla a khoheli a ka ntle le li-implants tse behiloeng sebakeng sa 'mele tse nang le hlahala li ka sebelisoa e le mohloli oa matla a khoheli.6 Mokhoa oa pele o na le mefokolo e tebileng, ho kopanyelletsa le tlhokahalo ea ho sebelisa thepa e khethehileng bakeng sa ho lebisa matla a khoheli a lithethefatsi le tlhokahalo ea ho koetlisa basebetsi ho etsa opereishene.Ho phaella moo, mokhoa ona o lekanyelitsoe ka litšenyehelo tse phahameng 'me o loketse feela lihlahala "tse holimo" tse haufi le holim'a' mele.Mokhoa o mong oa ho sebelisa li-implants tsa makenete o holisa boholo ba ts'ebeliso ea theknoloji ena, e nolofalletsa ts'ebeliso ea eona ho lihlahala tse likarolong tse fapaneng tsa 'mele.Ka bobeli limakete le limakenete tse kenyellelitsoeng ho intraluminal stent li ka sebelisoa e le li-implants bakeng sa tšenyo ea hlahala lithong tse se nang letho ho netefatsa patency ea tsona.Leha ho le joalo, ho ea ka lipatlisiso tsa rona tse sa hatisoang, tsena ha li matla ka ho lekaneng ho netefatsa hore MNP e bolokoa maling.
Katleho ea phano ea lithethefatsi ea magnetron e ipapisitse le lintlha tse ngata: litšoaneleho tsa mochini oa khoheli ka boeona, le litšoaneleho tsa mohloli oa matla a khoheli (ho kenyeletsoa likarolo tsa geometri tsa limakete tse sa feleng le matla a matla a khoheli ao ba a hlahisang).Nts'etsopele ea thekenoloji e atlehileng ea ho tsamaisa li-cell inhibitor e tsamaisoang ka matla e lokela ho kenyelletsa nts'etsopele ea li-magnetic nanoscale drug carriers, ho lekola polokeho ea bona, le ho theha protocol ea pono e lumellang ho latela metsamao ea bona 'meleng.
Thutong ena, ka lipalo re ile ra bala likarolo tse nepahetseng tsa matla a khoheli ho laola mojari oa lithethefatsi oa nano-scale 'meleng.Monyetla oa ho boloka MNP ka lerako la methapo ea mali tlas'a tšusumetso ea matla a khoheli a sebelisitsoeng a nang le litšobotsi tsena tsa computational e ile ea boela ea ithutoa ka methapo ea mali ea likhoto tse ka thōko.Ho feta moo, re ile ra kopanya li-conjugate tsa li-MNP le li-agent tsa fluorescent 'me ra etsa protocol bakeng sa pono ea bona ka vivo.Tlas'a maemo a vivo, ho litoeba tsa mohlala oa tumor, katleho ea ho bokella li-MNP ka har'a lisele tsa tumor ha li tsamaisoa ka mokhoa o hlophisitsoeng tlas'a tšusumetso ea matla a khoheli e ile ea ithutoa.
Thutong ea in vitro, re sebelisitse MNP ea referense, 'me thutong ea in vivo, re sebelisitse MNP e tlotsitsoeng ka lactic acid polyester (polylactic acid, PLA) e nang le fluorescent agent (indolecyanine; ICG).MNP-ICG e kenyelelitsoe ho Tabeng, sebelisa (MNP-PLA-EDA-ICG).
Sebopeho le sebopeho sa 'mele le lik'hemik'hale tsa MNP li hlalositsoe ka botlalo libakeng tse ling.7,8
E le ho kopanya MNPs-ICG, li-conjugate tsa PLA-ICG li ile tsa hlahisoa pele.Ho ile ha sebelisoa motsoako oa phofo oa racemic oa PLA-D le PLA-L o nang le boima ba molek'hule oa 60 kDa.
Kaha PLA le ICG ke li-acids ka bobeli, molemong oa ho kopanya li-conjugate tsa PLA-ICG, ho hlokahala pele ho kopanya spacer e felisitsoeng ke amino ho PLA, e thusang ICG chemisorb ho spacer.The spacer e entsoe ka ho sebelisa ethylene diamine (EDA), mokhoa oa carbodiimide le carbodiimide e qhibilihang ka metsing, 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide (EDAC).PLA-EDA spacer e entsoe ka tsela e latelang.Eketsa ka makhetlo a 20 molar e feteletseng ea EDA le 20-fold molar over EDAC ho 2 mL ea 0.1 g/mL PLA chloroform solution.Sehlahisoa se entsoe ka 15 mL polypropylene test tube holim'a shaker ka lebelo la 300 min-1 bakeng sa lihora tse peli.Morero oa ho kopanya o bontšoa ho Setšoantšo sa 1. Pheta motsoako ka makhetlo a 200 a feteletseng a li-reagents ho ntlafatsa leano la ho kopanya.
Qetellong ea motsoako, tharollo e ne e le centrifuged ka lebelo la 3000 min-1 bakeng sa metsotso ea 5 ho tlosa lihlahisoa tse ngata tsa polyethylene.Joale, 2 mL ea 0.5 mg/mL tharollo ea ICG ka dimethyl sulfoxide (DMSO) e ile ea kenngoa ho tharollo ea 2 mL.Agitator e tsitsitsoe ka lebelo le susumetsang la 300 min-1 bakeng sa lihora tse peli.Setšoantšo sa schematic sa conjugate e fumanoeng se bontšoa ho Setšoantšo sa 2.
Ka 200 mg MNP, re kentse 4 mL PLA-EDA-ICG conjugate.Sebelisa LS-220 shaker (LOIP, Russia) ho hlohlelletsa ho emisoa ka metsotso e 30 ka makhetlo a 300 min-1.Ka mor'a moo, e ile ea hlatsuoa ka isopropanol ka makhetlo a mararo 'me ea aroloa ka matla a khoheli.Sebelisa UZD-2 Ultrasonic Disperser (FSUE NII TVCH, Russia) ho eketsa IPA ho emisoa bakeng sa metsotso ea 5-10 tlas'a ketso e tsoelang pele ea ultrasonic.Ka mor'a ho hlatsoa IPA ea boraro, metsi a hlatsuoa a hlatsuoa ka metsi a hloekisitsoeng 'me a khutlisetsoa ka letsoai la physiological ka bongata ba 2 mg / mL.
Thepa ea ZetaSizer Ultra (Malvern Instruments, UK) e ne e sebelisetsoa ho ithuta kabo ea boholo ba MNP e fumanoeng ka tharollo ea metsi.Sebonela-hōle sa electron microscope (TEM) se nang le JEM-1400 STEM field emission cathode (JEOL, Japane) se ile sa sebelisoa ho ithuta sebōpeho le boholo ba MNP.
Thutong ena, re sebelisa limmanete tse sa feleng tsa cylindrical (N35 grade; e nang le litlolo tse sireletsang nickel) le boholo bo latelang bo tloaelehileng (bolelele ba bolelele ba × cylinder bophara): 0.5 × 2 mm, 2 × 2 mm, 3 × 2 mm le 5 × 2 mm.
Thuto ea in vitro ea lipalangoang tsa MNP tsamaisong ea mohlala e ile ea etsoa ka scaffold ea hydrodynamic e entsoeng ke Institute of Experimental Medicine ea Almazov State Medical Research Center ea Lekala la Bophelo la Russia.Bophahamo ba mokelikeli o potolohang (metsi a hloekisitsoeng kapa tharollo ea Krebs-Henseleit) ke 225 ml.Axially magnetized cylindrical magnets e sebelisoa e le limakenete tse sa feleng.Beha makenete holim'a sets'oants'o sa 1.5 mm hole le lebota le kahare la phaephe ea khalase e bohareng, 'me pheletso ea eona e shebane le tataiso ea tube (e theohileng).Sekhahla sa phallo ea mokelikeli ka har'a lupu e koetsoeng ke 60 L / h (e tsamaellanang le lebelo la mola oa 0.225 m / s).Tharollo ea Krebs-Henseleit e sebelisoa e le mokelikeli o potolohang hobane ke analoge ea plasma.The dynamic viscosity coefficient of plasma ke 1.1-1.3 mPa∙s.9 Palo ea MNP e bapalitsoeng ho matla a khoheli e khethoa ke spectrophotometry ho tloha ho tsitsipano ea tšepe mokelikeli o potolohang ka mor'a teko.
Ho feta moo, liphuputso tsa liteko li entsoe tafoleng ea mechanics e ntlafalitsoeng ea mokelikeli ho fumana hore na methapo ea mali e kenella hakae.Likarolo tse ka sehloohong tsa tšehetso ea hydrodynamic li bontšoa ho Setšoantšo sa 3. Likarolo tse ka sehloohong tsa stent ea hydrodynamic ke sekoti se koetsoeng se etsisang karolo ea sefapano sa tsamaiso ea methapo ea mohlala le tanka ea polokelo.Ho tsamaea ha mokelikeli oa mohlala haufi le mokoloko oa mojule oa methapo ea mali ho fanoa ke pompo ea peristaltic.Nakong ea teko, boloka mouoane le mocheso o hlokahalang, 'me u hlokomele liparamente tsa tsamaiso (mocheso, khatello, sekhahla sa phallo ea metsi, le pH boleng).
Setšoantšo sa 3 Block diagram ea setup e sebelisetsoang ho ithuta ho phunyeletsa ha lebota la methapo ea carotid.Tanka ea polokelo e le 1, pompo ea 2-peristaltic, 3-mokhoa oa ho kenyelletsa ho emisoa ho nang le MNP ka har'a lupu, 4-flow meter, 5-pressure sensor in the loop, 6-heat exchanger, kamore e 7 e nang le setshelo, 8-mohloli ea matla a khoheli, 9-balune e nang le li-hydrocarbon.
Kamore e nang le setshelo e na le lijana tse tharo: sejana se seholo sa ka ntle le lijana tse peli tse nyenyane, tseo matsoho a potoloho e bohareng a fetang ho tsona.Cannula e kenngoa ka har'a sets'oants'o se senyenyane, sets'oants'o se kenngoa ka likhoele holim'a setshelo se senyenyane, 'me ntlha ea cannula e tlameletsoe ka thata ka terata e tšesaane.Sebaka se pakeng tsa setshelo se seholo le sejana se senyenyane se tletse metsi a silafetseng, 'me mocheso o lula o le teng ka lebaka la ho amana le mocheso oa mocheso.Sebaka se ka har'a setshelo se senyenyane se tletse tharollo ea Krebs-Henseleit ho boloka ts'ebetso ea lisele tsa methapo ea mali.Tanka e boetse e tletse tharollo ea Krebs-Henseleit.Sistimi ea phepelo ea khase (khabone) e sebelisetsoa ho etsa mouoane oa tharollo ka har'a setshelo se senyane ka tanka ea polokelo le phaposi e nang le setshelo (Setšoantšo sa 4).
Setšoantšo sa 4 Kamore eo setshelo se behoang ho sona.1-Cannula bakeng sa ho theola methapo ea mali, kamore ea 2-Outer, 3-Kamore e nyane.Motsu o bontša tataiso ea mokelikeli oa mohlala.
Ho fumana hore na ho na le index e lekanyelitsoeng ea "permeability") ea lebota la sekepe, ho ile ha sebelisoa mothapo oa rat carotid.
Kenyelletso ea ho emisoa ha MNP (0.5mL) ka har'a sistimi e na le litšoaneleho tse latelang: kakaretso ea ka hare ea tanka le phala e kopanyang ka loop ke 20mL, 'me molumo o ka hare oa kamore ka' ngoe ke 120mL.Mohloli oa matla a khoheli a kantle ke makenete e sa feleng e nang le boholo bo tloaelehileng ba 2 × 3 mm.E kenngoa ka holim'a e 'ngoe ea likamore tse nyenyane, 1 cm ho tloha setshelo, 'me ntlha e' ngoe e shebane le lerako la lijana.Mocheso o bolokoa ho 37°C.Matla a pompo ea rolara a behiloe ho 50%, e lumellanang le lebelo la 17 cm / s.E le taolo, lisampole li nkiloe ka seleng e se nang limakete tse sa feleng.
Hora e le 'ngoe ka mor'a tsamaiso ea khatello e fanoeng ea MNP, ho ile ha nkoa sampole ea metsi ho tsoa phaposing.Motsoako oa likaroloana o lekantsoe ka spectrophotometer ho sebelisa Unico 2802S UV-Vis spectrophotometer (United Products & Instruments, USA).Ha ho nahanoa ka sekhahla sa ho monya ha MNP ho emisoa, tekanyo e entsoe ho 450 nm.
Ho ea ka litataiso tsa Rus-LASA-FELASA, liphoofolo tsohle li holisoa le ho hōlisetsoa libakeng tse khethehileng tse se nang likokoana-hloko.Phuputso ena e ikamahanya le melao eohle e amehang ea boitšoaro bakeng sa liteko le lipatlisiso tsa liphoofolo, 'me e fumane tumello ea boitšoaro ho tsoa Setsing sa Sechaba sa Lipatlisiso sa Bongaka sa Almazov (IACUC).Liphoofolo li ne li noa metsi ad libitum 'me li fepa kamehla.
Boithuto bona bo entsoe ho litoeba tse 10 tse nang le li-anesthetized tsa libeke tse 12 tsa NSG (NOD.Cg-Prkdcscid Il2rgtm1Wjl/Szj, Jackson Laboratory, USA) 10, tse boima ba 22 g ± 10%.Kaha ho itšireletsa ha litoeba tsa immunodeficiency ho hatelloa, litoeba tsa immunodeficiency tsa mohala ona li lumella ho fetisoa ha lisele tsa motho le lisele ntle le ho hana transplant.Littermates tse tsoang likoahelong tse fapaneng li ile tsa abeloa sehlopha sa liteko ka mokhoa o sa reroang, 'me li ne li kopane kapa li pepesitsoe ka mokhoa o hlophisehileng malaong a lihlopha tse ling ho etsa bonnete ba ho pepeseha ho lekanang ho microbiota e tloaelehileng.
Mohala oa lisele tsa mofetše oa HeLa o sebelisoa ho theha mohlala oa xenograft.Lisele li ne li entsoe ka DMEM e nang le glutamine (PanEco, Russia), e tlatsitsoeng ka 10% fetal bovine serum (Hyclone, USA), 100 CFU / mL penicillin, le 100 μg / mL streptomycin.Mohala oa sele o ile oa fanoa ka mosa ke Gene Expression Regulation Laboratory ea Institute of Cell Research ea Russian Academy of Sciences.Pele ho ente, lisele tsa HeLa li ne li ntšoa ka polasetiki ea setso ka 1: 1 trypsin: tharollo ea Versene (Biolot, Russia).Ka mor'a ho hlatsuoa, lisele li ne li fanyehiloe ka mokhoa o feletseng ho ea ho motsoako oa lisele tse 5 × 106 ka 200 μL, 'me li hlapolotsoe ka membrane e ka tlas'a lefatše (LDEV-FREE, MATRIGEL® CORNING®) (1: 1, holim'a leqhoa).Ho emisoa ha sele ho lokiselitsoeng ho ile ha kenngoa ka tlas'a letlalo la serope sa mouse.Sebelisa li-caliper tsa elektroniki ho lekola kholo ea hlahala matsatsing a mang le a mang a 3.
Ha hlahala e fihla ho 500 mm3, makenete e sa feleng e ile ea kenngoa ka har'a mesifa ea phoofolo ea liteko haufi le hlahala.Sehlopheng sa liteko (MNPs-ICG + tumor-M), 0.1 mL ea ho emisoa ha MNP e ile ea kenngoa 'me ea pepesetsoa matla a khoheli.Liphoofolo tse feletseng tse sa phekoloang li ne li sebelisoa e le li-control (background).Ho feta moo, liphoofolo tse kentsoeng ka 0.1 mL ea MNP empa li sa kenngoa ka limmete (MNPs-ICG + tumor-BM) li ile tsa sebelisoa.
Ponahalo ea fluorescence ea lisampole tsa in vivo le in vitro e entsoe ho IVIS Lumina LT Series III bioimager (PerkinElmer Inc., USA).Bakeng sa pono ea in vitro, palo ea 1 mL ea synthetic PLA-EDA-ICG le MNP-PLA-EDA-ICG conjugate e ile ea eketsoa lilibeng tsa lipoleiti.Ha ho nahanoa ka litšobotsi tsa fluorescence tsa dae ea ICG, filthara e ntle ka ho fetisisa e sebelisetsoang ho fumana matla a khanyang a sampole e khethiloe: boholo ba maqhubu a excitation ke 745 nm, 'me bophahamo ba maqhubu ke 815 nm.The Living Image 4.5.5 software (PerkinElmer Inc.) e ne e sebelisetsoa ho lekanya ka bongata matla a fluorescence a liliba tse nang le conjugate.
Matla a fluorescence le ho bokellana ha MNP-PLA-EDA-ICG conjugate li ile tsa lekanngoa ka litoeba tsa mohlala oa tumor, ntle le ho ba teng le ho sebelisoa ha matla a khoheli sebakeng sa thahasello.Litoeba li ile tsa hlajoa ka isoflurane, 'me 0.1 mL ea conjugate ea MNP-PLA-EDA-ICG e ile ea kenngoa ka mothapo oa mohatla.Litoeba tse sa phekoloang li ne li sebelisoa e le taolo e mpe ho fumana mokokotlo oa fluorescent.Ka mor'a ho tsamaisa conjugate ka methapo, beha phoofolo sebakeng sa ho futhumatsa (37 ° C) ka kamoreng ea IVIS Lumina LT series III fluorescence imager (PerkinElmer Inc.) ha u ntse u boloka inhalation ka 2% isoflurane anaesthetization.Sebelisa sefe e ahelletsoeng ka hare ho ICG (745–815 nm) bakeng sa ho lemoha mats'oao motsotso o le mong le metsotso e 15 kamora ho hlahisoa ha MNP.
Ho hlahloba ho bokellana ha conjugate ka har'a hlahala, sebaka sa peritoneal sa phoofolo se ne se koahetsoe ka pampiri, e leng se ileng sa etsa hore ho khonehe ho felisa fluorescence e khanyang e amanang le ho bokella likaroloana sebeteng.Ka mor'a ho ithuta ka biodistribution ea MNP-PLA-EDA-ICG, liphoofolo li ile tsa hlajoa ke botho ka ho feteletsa ha isoflurane anesthesia bakeng sa karohano e latelang ea libaka tsa hlahala le tlhahlobo ea bongata ba mahlaseli a fluorescence.Sebelisa Living Image 4.5.5 software (PerkinElmer Inc.) ho sebetsa ka letsoho tlhahlobo ea matšoao ho tloha sebakeng se khethiloeng sa thahasello.Ho ile ha nkoa litekanyo tse tharo bakeng sa phoofolo ka 'ngoe (n = 9).
Phuputsong ena, ha rea ​​ka ra lekanya katleho e atlehileng ea ICG ho MNPs-ICG.Ho phaella moo, ha rea ​​ka ra bapisa katleho ea ho boloka li-nanoparticles tlas'a tšusumetso ea limatlase tse sa feleng tsa libopeho tse fapaneng.Ho feta moo, ha rea ​​ka ra lekola phello ea nako e telele ea matla a khoheli ho bolokoeng ha li-nanoparticles liseleng tsa tumor.
Li-nanoparticles li laola, ka boholo ba karolelano ea 195.4 nm.Ho phaella moo, ho emisoa ho ne ho e-na le li-agglomerates tse nang le boholo ba karolelano ea 1176.0 nm (Figure 5A).Ka mor'a moo, karolo eo e ile ea hloekisoa ka sefe ea centrifugal.Matla a zeta a likaroloana ke -15.69 mV (Setšoantšo sa 5B).
Setšoantšo sa 5 Thepa ea 'mele ea ho emisoa: (A) kabo ea boholo ba likaroloana;(B) kabo ea likaroloana ka bokhoni ba zeta;(C) foto ea TEM ea nanoparticles.
The particle size ha e le hantle 200 nm (Figure 5C), e entsoe ka MNP e le 'ngoe ka boholo ba 20 nm, le PLA-EDA-ICG conjugated organic khetla le tlaase elektrone segokanyipalo.Sebopeho sa li-agglomerate ka tharollo ea metsi e ka hlalosoang ke modulus e batlang e le tlaase ea matla a motlakase a nanoparticles ka bomong.
Bakeng sa limakete tse sa feleng, ha magnetization e tsepamisitsoe molumong oa V, polelo ea bohlokoa e arotsoe ka likarolo tse peli, e leng bophahamo le bokaholimo:
Tabeng ea sampuli e nang le magnetization ea kamehla, boima ba hona joale ke zero.Joale, polelo ea "magnetic induction vector" e tla nka sebopeho se latelang:
Sebelisa lenaneo la MATLAB (MathWorks, Inc., USA) bakeng sa lipalo, nomoro ea laesense ea thuto ea ETU "LETI" 40502181.
Joalokaha ho bontšitsoe setšoantšong sa 7 Setšoantšo sa 8 Setšoantšo sa 9 Setšoantšo-10, matla a khoheli a matla ka ho fetisisa a hlahisoa ke magnet oriented axially ho tloha qetellong ea cylinder.Radius e sebetsang ea ketso e lekana le geometry ea makenete.Limaketeng tsa cylindrical tse nang le cylinder eo bolelele ba eona bo leng boholo ho feta bophara ba eona, matla a matla a khoheli a bonoa ka tataiso ea axial-radial (bakeng sa karolo e lumellanang);ka hona, li-cylinders tse nang le karolo e kholoanyane ea likarolo (bophara le bolelele) MNP adsorption ke eona e sebetsang ka ho fetisisa.
Setšoantšo sa 7 Karolo ea matla a khoheli a khoheli Bz hammoho le axis ea Oz ea makenete;tekanyo e tloaelehileng ea makenete: mohala o motšo 0.5 × 2mm, mola o moputsoa 2 × 2mm, mola o motala 3 × 2mm, mohala o mofubelu 5 × 2mm.
Setšoantšo sa 8 Karolo ea induction ea makenete Br e perpendicular ho magnet axis Oz;tekanyo e tloaelehileng ea makenete: mohala o motšo 0.5 × 2mm, mola o moputsoa 2 × 2mm, mola o motala 3 × 2mm, mohala o mofubelu 5 × 2mm.
Setšoantšo sa 9 The magnetic induction intensity Bz karolo ea bohole r ho tloha qetellong ea axis ea makenete (z=0);tekanyo e tloaelehileng ea makenete: mohala o motšo 0.5 × 2mm, mola o moputsoa 2 × 2mm, mola o motala 3 × 2mm, mohala o mofubelu 5 × 2mm.
Setšoantšo sa 10 Karolo ea Magnetic induction ho latela tataiso ea radial;boholo bo tloaelehileng ba makenete: mohala o motšo 0.5 × 2mm, mola o moputsoa 2 × 2mm, mola o motala 3 × 2mm, mohala o mofubelu 5 × 2mm.
Mefuta e khethehileng ea hydrodynamic e ka sebelisoa ho ithuta mokhoa oa ho fana ka MNP ho lisele tsa tumor, ho tsepamisa maikutlo ho nanoparticles sebakeng se lebisitsoeng, le ho tseba hore na nanoparticles e itšoara joang tlas'a maemo a hydrodynamic tsamaisong ea potoloho ea mali.Limanete tse sa feleng li ka sebelisoa e le matla a khoheli a kantle.Haeba re hlokomoloha tšebelisano ea magnetostatic pakeng tsa nanoparticles 'me re sa nahane ka mohlala oa mokelikeli oa makenete, ho lekane ho hakanya ho sebelisana pakeng tsa makenete le nanoparticle e le' ngoe e nang le tekanyo ea dipole-dipole.
Moo m e leng nako ea makenete ea makenete, r ke radius vector ea moo nanoparticle e leng teng, 'me k ke eona sistimi.Ka tekanyo ea dipole, tšimo ea makenete e na le tlhophiso e tšoanang (Setšoantšo sa 11).
Sebakeng se ts'oanang sa makenete, li-nanoparticles li potoloha feela meleng ea matla.Sebakeng sa matla a khoheli a sa ts'oaneng, matla a sebetsa ho ona:
E kae derivative ea tataiso e fanoeng l.Ho phaella moo, matla a hula li-nanoparticles libakeng tse sa tšoaneng ka ho fetisisa tsa tšimo, ke hore, ho kobeha le ho teteka ha mela ea matla ho eketseha.
Ka hona, ke ntho e lakatsehang ho sebelisa makenete e matla ka ho lekaneng (kapa ketane ea makenete) e nang le axial anisotropy e hlakileng sebakeng seo likaroloana li leng teng.
Letlapa la 1 le bonts'a bokhoni ba makenete e le 'ngoe e le mohloli o lekaneng oa matla a khoheli ho tšoara le ho boloka MNP betheng ea methapo ea sebaka sa kopo.