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Sau npe rau koj cov ntsiab lus tshwj xeeb thiab cov tshuaj tshwj xeeb uas txaus siab, thiab peb yuav phim cov ntaub ntawv koj muab nrog cov ntawv hauv peb cov ntaub ntawv dav dav thiab xa koj daim ntawv PDF ntawm email raws sijhawm.
Tswj kev txav ntawm cov hlau nplaum hlau oxide nanoparticles rau kev xa khoom ntawm cytostatics
Sau 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 Demidov6,71 Almazov National Medical Kev tshawb fawb Center ntawm Ministry of Health ntawm Lavxias teb sab Federation, St. Petersburg, 197341, Lavxias teb sab Federation;2 St. Petersburg Electrotechnical University “LETI”, St. Petersburg, 197376, Lavxias teb sab Federation;3 Center for Personalized Medicine, Almazov State Medical Research Center, Ministry of Health ntawm Lavxias teb sab Federation, St. Petersburg, 197341, Russia Federation;4FSBI "Influenza Research Institute muaj npe tom qab AA Smorodintsev" Ministry of Health ntawm Lavxias teb sab Federation, St. Petersburg, Lavxias teb sab Federation;5 Sechenov lub koom haum ntawm Evolutionary Physiology thiab Biochemistry, Lavxias teb sab Academy ntawm Sciences, St. Petersburg, Lavxias teb sab Federation;6 RAS lub koom haum ntawm Cytology, St. Petersburg, 194064, Lavxias teb sab Federation;7INSERM U1231, Kws Qhia Ntawv ntawm Tshuaj thiab Pharmacy, Bourgogne-Franche Comté University of Dijon, Fabkis Kev Sib Txuas Lus: Yana ToropovaAlmazov National Medical Research Center, Ministry of Health ntawm Lavxias teb sab Federation, Saint-Petersburg, 197341, Lavxias Federation Tel +7 981 95269706 4 [email tiv thaiv] keeb kwm yav dhau: Ib txoj hauv kev zoo rau qhov teeb meem ntawm cytostatic toxicity yog kev siv cov hlau nplaum nanoparticles (MNP) rau kev xa tshuaj.Lub Hom Phiaj: Siv cov kev suav los txiav txim siab cov yam ntxwv zoo tshaj plaws ntawm cov hlau nplaum uas tswj MNPs hauv vivo, thiab ntsuas qhov ua tau zoo ntawm kev xa cov hlau nplaum ntawm MNPs rau nas qog hauv vitro thiab hauv vivo.(MNPs-ICG) yog siv.Hauv vivo luminescence siv cov kev tshawb fawb tau ua hauv cov nas nas, nrog thiab tsis muaj qhov sib nqus ntawm qhov chaw txaus siab.Cov kev tshawb fawb no tau ua los ntawm hydrodynamic scaffold tsim los ntawm lub koom haum ntawm Kev Tshawb Fawb Tshuaj ntawm Almazov State Medical Research Center ntawm Lavxias Ministry of Health.Qhov tshwm sim: Kev siv cov hlau nplaum neodymium txhawb nqa kev xaiv ntawm MNP.Ib feeb tom qab kev tswj hwm ntawm MNPs-ICG rau cov nas qog nqaij hlav, MNPs-ICG feem ntau khaws cia hauv daim siab.Nyob rau hauv tsis muaj thiab muaj ib tug magnetic teb, qhov no qhia nws txoj kev metabolic.Txawm hais tias qhov nce ntawm fluorescence nyob rau hauv cov qog tau pom nyob rau hauv lub xub ntiag ntawm ib tug magnetic teb, lub fluorescence siv nyob rau hauv lub siab ntawm tus tsiaj tsis hloov lub sij hawm.Cov ntsiab lus: Hom MNP no, ua ke nrog kev ntsuas qhov sib nqus ntawm lub zog, tuaj yeem ua lub hauv paus rau kev txhim kho cov hlau nplaum tswj cov tshuaj cytostatic rau cov qog nqaij hlav.Keywords: fluorescence tsom xam, indocyanine, hlau oxide nanoparticles, magnetron xa ntawm cytostatics, qog targeting
Cov kab mob qog nqaij hlav yog ib qho tseem ceeb ntawm kev tuag thoob ntiaj teb.Nyob rau tib lub sijhawm, qhov kev hloov pauv ntawm kev mob hnyav zuj zus thiab kev tuag ntawm cov kab mob qog tseem muaj nyob.1 Cov kws khomob siv niaj hnub no tseem yog ib qho kev kho mob tseem ceeb rau cov qog nqaij hlav sib txawv.Nyob rau tib lub sijhawm, kev txhim kho ntawm txoj hauv kev los txo cov kab mob toxicity ntawm cytostatics tseem cuam tshuam.Ib txoj hauv kev zoo los daws nws cov teeb meem toxicity yog siv cov nano-scale nqa mus rau lub hom phiaj kev xa tshuaj, uas tuaj yeem muab cov tshuaj sib xyaw hauv zos hauv cov qog nqaij hlav tsis tas yuav ua rau lawv cov khoom sib xyaw ua ke hauv lub cev thiab cov ntaub so ntswg.concentration.2 Txoj kev no ua rau nws muaj peev xwm txhim kho qhov ua tau zoo thiab lub hom phiaj ntawm cov tshuaj chemotherapeutic ntawm cov qog nqaij hlav, thaum txo lawv cov kab mob toxicity.
Ntawm cov ntau yam nanoparticles txiav txim siab rau lub hom phiaj xa khoom ntawm cytostatic cov neeg ua haujlwm, cov khoom sib nqus nanoparticles (MNPs) yog qhov txaus siab tshwj xeeb vim lawv cov khoom siv tshwj xeeb, lom neeg, thiab sib nqus, uas ua kom lawv muaj peev xwm.Yog li ntawd, cov hlau nplaum nanoparticles tuaj yeem siv los ua cov cua sov los kho cov qog nrog hyperthermia (magnetic hyperthermia).Lawv kuj tuaj yeem siv los ua cov tshuaj tiv thaiv kab mob (magnetic resonance diagnosis).3-5 Siv cov yam ntxwv no, ua ke nrog qhov muaj peev xwm ntawm MNP tsub zuj zuj hauv ib cheeb tsam tshwj xeeb, los ntawm kev siv cov khoom sib nqus sab nraud, kev xa khoom ntawm cov tshuaj npaj npaj tau qhib rau kev tsim cov kab ke sib nqus magnetron rau lub hom phiaj cytostatics rau cov qog nqaij hlav. Kev cia siab.Cov txheej txheem zoo li no yuav suav nrog MNP thiab magnetic teb los tswj lawv lub zog hauv lub cev.Nyob rau hauv rooj plaub no, ob qho tib si sab nraud magnetic teb thiab magnetic implants muab tso rau hauv lub cev cheeb tsam uas muaj cov qog yuav siv tau raws li qhov chaw ntawm lub magnetic teb.6 Thawj txoj kev muaj qhov tsis zoo, suav nrog kev xav tau siv cov cuab yeej tshwj xeeb rau kev sib nqus cov hom phiaj ntawm cov tshuaj thiab yuav tsum tau cob qhia cov neeg ua haujlwm los ua kev phais.Tsis tas li ntawd, txoj kev no yog txwv los ntawm tus nqi siab thiab tsuas yog tsim nyog rau cov qog "superficial" ze rau ntawm lub cev.Lwm txoj hauv kev ntawm kev siv cov hlau nplaum sib nqus nthuav dav ntawm daim ntawv thov ntawm cov thev naus laus zis no, ua kom yooj yim rau nws siv ntawm cov qog nyob hauv ntau qhov chaw ntawm lub cev.Ob leeg cov hlau nplaum thiab cov hlau nplaum sib xyaw ua ke rau hauv intraluminal stent tuaj yeem siv los ua kev cog qoob loo rau cov qog nqaij hlav hauv lub cev hollow kom ntseeg tau tias lawv patency.Txawm li cas los xij, raws li peb tus kheej cov kev tshawb fawb uas tsis tau tshaj tawm, cov no tsis muaj cov hlau nplaum txaus los xyuas kom meej qhov tuav ntawm MNP los ntawm cov hlab ntsha.
Qhov ua tau zoo ntawm kev xa cov tshuaj magnetron nyob ntawm ntau yam: cov yam ntxwv ntawm cov khoom siv hlau nplaum nws tus kheej, thiab cov yam ntxwv ntawm qhov chaw sib nqus (xws li cov duab geometric ntawm cov hlau nplaum ruaj khov thiab lub zog ntawm cov hlau nplaum lawv tsim).Txoj kev loj hlob ntawm kev vam meej magnetically coj cell inhibitor kev xa khoom thev naus laus zis yuav tsum koom nrog kev tsim cov tshuaj sib nqus nanoscale tsim nyog, ntsuas lawv txoj kev nyab xeeb, thiab tsim cov txheej txheem kev pom pom uas tso cai rau taug qab lawv cov kev txav hauv lub cev.
Nyob rau hauv txoj kev tshawb no, peb ua lej suav qhov zoo tshaj plaws magnetic teb cov yam ntxwv los tswj cov hlau nplaum nano-scale cov tshuaj hauv lub cev.Qhov muaj peev xwm khaws tau MNP los ntawm cov hlab ntsha phab ntsa nyob rau hauv kev cuam tshuam ntawm kev siv magnetic teb nrog cov kev suav cov yam ntxwv no kuj tau kawm nyob rau hauv cov hlab ntsha cais.Tsis tas li ntawd, peb tau tsim cov kev sib txuas ntawm MNPs thiab cov tshuaj fluorescent thiab tsim cov txheej txheem rau lawv qhov kev pom hauv vivo.Raws li nyob rau hauv vivo tej yam kev mob, nyob rau hauv cov qog qauv nas, tsub zuj zuj efficiency ntawm MNPs nyob rau hauv cov ntaub so ntswg hlav thaum muab systemically nyob rau hauv lub zog ntawm ib tug magnetic teb tau kawm.
Hauv kev tshawb fawb hauv vitro, peb siv MNP siv, thiab hauv kev tshawb fawb hauv vivo, peb siv MNP coated nrog lactic acid polyester (polylactic acid, PLA) uas muaj cov tshuaj fluorescent (indolecyanine; ICG).MNP-ICG muaj nyob rau hauv rooj plaub, siv (MNP-PLA-EDA-ICG).
Kev sib txuas thiab lub cev thiab tshuaj lom neeg ntawm MNP tau piav qhia meej nyob rau lwm qhov.7,8 ib
Txhawm rau tsim cov MNPs-ICG, PLA-ICG conjugates tau tsim ua ntej.Cov hmoov sib tov sib xyaw ntawm PLA-D thiab PLA-L nrog qhov hnyav molecular ntawm 60 kDa tau siv.
Txij li thaum PLA thiab ICG yog ob qho tib si acids, txhawm rau txhawm rau tsim cov PLA-ICG conjugates, thawj zaug yuav tsum tau tsim cov amino-terminated spacer ntawm PLA, uas pab ICG chemisorb rau lub spacer.Lub spacer tau tsim los siv ethylene diamine (EDA), txoj kev carbodiimide thiab dej-soluble carbodiimide, 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDAC).PLA-EDA spacer yog synthesized raws li hauv qab no.Ntxiv 20-fold molar tshaj ntawm EDA thiab 20-fold molar tshaj ntawm EDAC rau 2 mL ntawm 0.1 g / mL PLA chloroform tov.Cov synthesis yog nqa tawm nyob rau hauv 15 mL polypropylene xeem raj ntawm ib tug shaker ntawm ib tug ceev ntawm 300 min-1 rau 2 teev.Cov txheej txheem synthesis yog qhia hauv daim duab 1. Rov ua dua qhov kev sib txuas nrog 200-fold tshaj ntawm cov reagents los ua kom zoo dua cov txheej txheem synthesis.
Thaum kawg ntawm kev sib txuas, cov tshuaj tau centrifuged ntawm qhov ceev ntawm 3000 min-1 rau 5 feeb kom tshem tawm cov dej ntau dhau ntawm polyethylene derivatives.Tom qab ntawd, 2 mL ntawm 0.5 mg / mL ICG tov hauv dimethyl sulfoxide (DMSO) tau ntxiv rau 2 mL tshuaj.Lub agitator yog tsau ntawm ib tug stirring ceev ntawm 300 min-1 rau 2 teev.Daim duab schematic ntawm qhov tau txais conjugate yog qhia hauv daim duab 2.
Hauv 200 mg MNP, peb ntxiv 4 mL PLA-EDA-ICG conjugate.Siv LS-220 shaker (LOIP, Russia) ua rau lub sijhawm ncua 30 feeb ntawm qhov zaus ntawm 300 min-1.Tom qab ntawd, nws raug ntxuav nrog isopropanol peb zaug thiab raug sib nqus sib cais.Siv UZD-2 Ultrasonic Disperser (FSUE NII TVCH, Russia) ntxiv IPA rau qhov ncua sij hawm rau 5-10 feeb nyob rau hauv kev ua ultrasonic txuas ntxiv.Tom qab qhov thib peb IPA ntxuav, cov precipitate tau ntxuav nrog dej distilled thiab resuspended nyob rau hauv physiological saline ntawm ib tug concentration ntawm 2 mg / mL.
Cov cuab yeej ZetaSizer Ultra (Malvern Instruments, UK) tau siv los kawm txog qhov loj me ntawm MNP tau txais hauv cov tshuaj aqueous.Lub tshuab hluav taws xob xa hluav taws xob (TEM) nrog JEM-1400 STEM teb emission cathode (JEOL, Nyiv) tau siv los kawm txog cov duab thiab qhov loj ntawm MNP.
Hauv txoj kev tshawb no, peb siv cov hlau nplaum ruaj khov cylindrical (qib N35; nrog cov nickel tiv thaiv txheej) thiab cov qauv hauv qab no (ntev axis ntev × lub tog raj kheej txoj kab uas hla): 0.5 × 2 hli, 2 × 2 hli, 3 × 2 hli thiab 5 × 2 mm.
Kev tshawb fawb hauv vitro ntawm MNP kev thauj mus los hauv cov qauv qauv tau ua tiav ntawm hydrodynamic scaffold tsim los ntawm Lub Tsev Haujlwm ntawm Kev Tshawb Fawb Tshuaj ntawm Almazov State Medical Research Center ntawm Lavxias Ministry of Health.Lub ntim ntawm cov kua circulating (dej distilled los yog Krebs-Henseleit tov) yog 225 mL.Axially magnetized cylindrical hlau nplaum yog siv los ua cov hlau nplaum ruaj khov.Muab cov hlau nplaum tso rau ntawm tus tuav 1.5 hli deb ntawm cov phab ntsa sab hauv ntawm lub raj iav hauv nruab nrab, nrog nws qhov kawg tig mus rau kev taw qhia ntawm lub raj ( ntsug).Cov kua dej ntws hauv lub voj kaw yog 60 L / h (raws li cov kab tawm tshaj tawm ntawm 0.225 m / s).Krebs-Henseleit tov yog siv raws li cov kua circulating vim nws yog ib qho analog ntawm plasma.Lub dynamic viscosity coefficient ntawm plasma yog 1.1-1.3 mPa∙s.9 Tus nqi ntawm MNP adsorbed nyob rau hauv lub magnetic teb yog txiav txim los ntawm spectrophotometric los ntawm cov concentration ntawm hlau nyob rau hauv lub circulating kua tom qab kev sim.
Tsis tas li ntawd, kev sim kev tshawb fawb tau ua tiav ntawm lub rooj kho cov kua dej txhim kho kom txiav txim siab qhov txheeb ze permeability ntawm cov hlab ntsha.Cov khoom tseem ceeb ntawm kev txhawb nqa hydrodynamic tau qhia hauv daim duab 3. Cov khoom tseem ceeb ntawm hydrodynamic stent yog ib lub voj kaw uas simulates qhov cross-section ntawm tus qauv vascular system thiab lub tank cia.Kev txav ntawm cov qauv kua dej raws li contour ntawm cov hlab ntsha module yog muab los ntawm lub twj tso kua mis peristaltic.Thaum lub sij hawm sim, tswj qhov vaporization thiab qhov ntsuas kub uas yuav tsum tau ua, thiab saib xyuas qhov ntsuas qhov system (kub, siab, kua ntws tus nqi, thiab pH tus nqi).
Daim duab 3 Thaiv daim duab ntawm kev teeb tsa siv los kawm txog permeability ntawm phab ntsa carotid artery.1-storage tank, 2-peristaltic twj tso kua mis, 3-mechanism rau qhia ncua kev kawm ntawv uas muaj MNP rau hauv lub voj, 4-flow meter, 5-siab sensor nyob rau hauv lub voj, 6-heat exchanger, 7-chamber nrog ntim, 8-qhov chaw ntawm lub magnetic teb, 9-lub zais pa nrog hydrocarbons.
Lub chamber uas muaj lub thawv muaj peb lub thawv: ib lub thawv loj sab nraud thiab ob lub thawv me me, los ntawm cov caj npab ntawm lub hauv paus Circuit Court dhau.Lub cannula yog muab tso rau hauv lub thawv me me, lub thawv yog hlua rau ntawm lub thawv me me, thiab lub hau ntawm lub cannula yog nruj nreem khi nrog ib txoj hlua nyias.Qhov chaw nruab nrab ntawm lub thawv loj thiab lub thawv me yog ntim nrog cov dej distilled, thiab qhov kub thiab txias nyob twj ywm vim yog kev sib txuas ntawm cov khoom siv hluav taws xob.Qhov chaw nyob rau hauv lub thawv me yog ntim nrog Krebs-Henseleit tov los tswj cov hlab ntsha ntawm cov hlab ntsha.Lub tank kuj tseem muaj cov tshuaj Krebs-Henseleit.Cov pa roj (carbon) cov khoom siv yog siv los vaporize cov tshuaj nyob rau hauv lub thawv me me nyob rau hauv lub tank cia thiab lub chamber uas muaj lub thawv (Daim duab 4).
Daim duab 4 Lub chamber uas muab tso rau hauv lub thawv.1-Cannula rau txo cov hlab ntsha, 2-Chamber Sab nrauv, 3-Chamber me.Lub xub taw qhia cov kev taw qhia ntawm cov qauv kua dej.
Txhawm rau txiav txim siab qhov txheeb ze permeability Performance index ntawm phab ntsa hlab ntsha, nas carotid hlab ntsha tau siv.
Kev taw qhia ntawm MNP ncua kev kawm ntawv (0.5mL) rau hauv lub cev muaj cov yam ntxwv hauv qab no: tag nrho cov ntim sab hauv ntawm lub tank thiab cov yeeb nkab txuas hauv lub voj yog 20mL, thiab cov ntim sab hauv ntawm txhua chav yog 120mL.Qhov chaw sib nqus sab nraud yog cov hlau nplaum ruaj khov nrog tus qauv loj ntawm 2 × 3 hli.Nws yog ntsia saum toj ntawm ib qho ntawm cov chav me me, 1 cm deb ntawm lub thawv, nrog rau ib qho kawg ntawm lub thawv phab ntsa.Qhov kub yog khaws cia ntawm 37 ° C.Lub zog ntawm cov twj tso kua mis yog teem rau 50%, uas sib haum mus rau qhov ceev ntawm 17 cm / s.Raws li kev tswj hwm, cov qauv raug coj mus rau hauv lub xov tooj ntawm tes yam tsis muaj hlau nplaum ruaj khov.
Ib teev tom qab kev tswj hwm ntawm ib qho kev qhia ntawm MNP, cov qauv ua kua tau raug coj los ntawm lub chamber.Lub particle concentration yog ntsuas los ntawm ib tug spectrophotometer siv Unico 2802S UV-Vis spectrophotometer (United Products & Instruments, USA).Muab rau hauv tus account qhov nqus spectrum ntawm MNP ncua kev kawm ntawv, qhov ntsuas tau ua ntawm 450 nm.
Raws li Rus-LASA-FELASA cov lus qhia, txhua tus tsiaj raug tsa thiab loj hlob hauv cov chaw tshwj xeeb uas tsis muaj kab mob.Txoj kev tshawb no ua raws li tag nrho cov kev cai coj ncaj ncees rau kev sim tsiaj thiab kev tshawb fawb, thiab tau txais kev pom zoo txog kev ncaj ncees los ntawm Almazov National Medical Research Center (IAACUC).Cov tsiaj haus dej ad libitum thiab noj tsis tu ncua.
Txoj kev tshawb no tau ua rau 10 tshuaj loog 12-lub lim tiam-laus txiv neej immunodeficient NSG nas (NOD.Cg-Prkdcscid Il2rgtm1Wjl/Szj, Jackson Laboratory, USA) 10, hnyav 22 g ± 10%.Txij li kev tiv thaiv kab mob ntawm cov nas tsis muaj zog tiv thaiv kab mob, cov nas tiv thaiv kab mob ntawm cov kab no tso cai rau kev hloov pauv ntawm tib neeg lub hlwb thiab cov ntaub so ntswg yam tsis muaj kev hloov pauv.Cov littermates los ntawm cov tawb sib txawv tau muab tso rau hauv pab pawg sim, thiab lawv tau sib koom ua ke los yog raug cuam tshuam rau hauv txaj ntawm lwm pab pawg kom ntseeg tau tias muaj kev sib npaug ntawm cov kab mob microbiota.
HeLa tib neeg kab mob qog noj ntshav yog siv los tsim ib qho qauv xenograft.Cov hlwb tau coj mus kuaj hauv DMEM uas muaj glutamine (PanEco, Russia), ntxiv nrog 10% fetal bovine serum (Hyclone, USA), 100 CFU / mL penicillin, thiab 100 μg / mL streptomycin.Cov kab ntawm tes tau ua siab zoo muab los ntawm Gene Expression Regulation Laboratory ntawm Lub Tsev Haujlwm Saib Xyuas Cell ntawm Lavxias Academy ntawm Kev Tshawb Fawb.Ua ntej txhaj tshuaj, HeLa hlwb raug tshem tawm ntawm kab lis kev cai yas nrog 1: 1 trypsin: Versene tov (Biolot, Russia).Tom qab ntxuav, cov hlwb raug tshem tawm hauv qhov nruab nrab kom ua tiav ntawm 5 × 106 hlwb ib 200 μL, thiab diluted nrog hauv qab daus daim nyias nyias (LDEV-DAWB, MATRIGEL® CORNING®) (1: 1, ntawm dej khov).Kev npaj ntawm tes raug tshem tawm tau txhaj subcutaneously rau hauv daim tawv nqaij ntawm tus ncej puab.Siv hluav taws xob calipers los soj ntsuam cov qog loj hlob txhua 3 hnub.
Thaum cov qog mus txog 500 mm3, cov hlau nplaum ruaj khov tau muab tso rau hauv cov leeg nqaij ntawm cov tsiaj sim ze ntawm cov qog.Hauv pab pawg sim (MNPs-ICG + qog-M), 0.1 mL ntawm MNP raug tshem tawm raug txhaj thiab raug rau qhov chaw sib nqus.Cov tsiaj tsis kho tag nrho tau siv los ua kev tswj hwm (tom qab).Tsis tas li ntawd, cov tsiaj txhaj tshuaj nrog 0.1 mL ntawm MNP tab sis tsis tau cog nrog cov hlau nplaum (MNPs-ICG + qog-BM) tau siv.
Kev kuaj pom fluorescence hauv vivo thiab hauv vitro kuaj tau ua nyob rau hauv IVIS Lumina LT series III bioimager (PerkinElmer Inc., USA).Rau kev pom hauv vitro, qhov ntim ntawm 1 mL ntawm hluavtaws PLA-EDA-ICG thiab MNP-PLA-EDA-ICG conjugate tau ntxiv rau lub phaj qhov dej.Muab rau hauv tus account cov yam ntxwv fluorescence ntawm ICG dye, qhov zoo tshaj plaws lim siv los txiav txim siab qhov kev siv ntawm cov qauv yog xaiv: qhov siab tshaj plaws excitation wavelength yog 745 nm, thiab emission wavelength yog 815 nm.Lub Neej Nyob 4.5.5 software (PerkinElmer Inc.) tau siv los ntsuas qhov fluorescence siv ntawm cov qhov dej uas muaj cov conjugate.
Cov fluorescence siv thiab tsub zuj zuj ntawm MNP-PLA-EDA-ICG conjugate tau ntsuas nyob rau hauv vivo qog qauv nas, tsis muaj lub xub ntiag thiab daim ntawv thov ntawm magnetic teb ntawm qhov chaw txaus siab.Cov nas raug tshuaj loog nrog isoflurane, thiab tom qab ntawd 0.1 mL ntawm MNP-PLA-EDA-ICG conjugate raug txhaj los ntawm tus Tsov tus tw leeg.Cov nas uas tsis kho tau raug siv los ua kev tswj tsis zoo kom tau txais keeb kwm fluorescent.Tom qab muab cov khoom sib xyaw ua ke, muab cov tsiaj tso rau ntawm qhov cua sov (37 ° C) hauv chav tsev ntawm IVIS Lumina LT series III fluorescence imager (PerkinElmer Inc.) thaum tswj kev nqus pa nrog 2% isoflurane anaesthetization.Siv ICG's built-in filter (745–815 nm) rau kev kuaj pom lub teeb liab 1 feeb thiab 15 feeb tom qab kev taw qhia ntawm MNP.
Txhawm rau ntsuas qhov sib xyaw ntawm cov kab mob hauv cov qog, thaj chaw peritoneal ntawm tus tsiaj tau npog nrog ntawv, uas ua rau nws muaj peev xwm tshem tawm cov fluorescence ci ntsa iab cuam tshuam nrog kev sib sau ntawm cov khoom hauv daim siab.Tom qab kawm txog biodistribution ntawm MNP-PLA-EDA-ICG, cov tsiaj tau humanely euthanized los ntawm overdose ntawm isoflurane anesthesia rau tom qab sib cais ntawm cov qog nqaij hlav thiab ntau npaum li cas ntawm fluorescence hluav taws xob.Siv Cov Duab Nyob Hauv 4.5.5 software (PerkinElmer Inc.) kom ua tiav cov teeb liab tsom xam los ntawm cheeb tsam xaiv nyiam.Peb qhov ntsuas tau raug coj los rau txhua tus tsiaj (n = 9).
Hauv txoj kev tshawb no, peb tsis tau txheeb xyuas qhov ua tiav ntawm kev thauj khoom ntawm ICG ntawm MNPs-ICG.Tsis tas li ntawd, peb tsis tau muab piv rau kev khaws cia ntawm nanoparticles nyob rau hauv lub zog ntawm cov hlau nplaum ruaj khov ntawm cov duab sib txawv.Tsis tas li ntawd, peb tsis tau soj ntsuam cov txiaj ntsig ntev ntawm cov hlau nplaum ntawm kev tuav cov nanoparticles hauv cov ntaub so ntswg.
Nanoparticles dominate, nrog qhov nruab nrab loj ntawm 195.4 nm.Tsis tas li ntawd, qhov ncua kev kawm ntawv muaj agglomerates nrog qhov nruab nrab loj ntawm 1176.0 nm (Daim duab 5A).Tom qab ntawd, qhov seem tau lim los ntawm lub centrifugal lim.Lub peev xwm zeta ntawm cov khoom yog -15.69 mV (Daim duab 5B).
Daim duab 5 Lub cev muaj zog ntawm kev ncua: (A) particle loj faib;(B) particle faib ntawm zeta muaj peev xwm;(C) TEM duab ntawm nanoparticles.
Qhov loj me me yog qhov pib ntawm 200 nm (Daim duab 5C), tsim los ntawm ib qho MNP nrog qhov loj ntawm 20 nm, thiab PLA-EDA-ICG conjugated organic plhaub nrog qis electron ceev.Kev tsim cov agglomerates hauv cov kev daws teeb meem aqueous tuaj yeem piav qhia los ntawm qhov tsis tshua muaj modulus ntawm electromotive quab yuam ntawm tus kheej nanoparticles.
Rau cov hlau nplaum tas mus li, thaum lub magnetization yog concentrated nyob rau hauv lub ntim V, lub ntsiab lus qhia tau muab faib ua ob qho tib si, uas yog lub ntim thiab qhov chaw:
Nyob rau hauv cov ntaub ntawv ntawm ib tug qauv nrog ib tug tas li magnetization, qhov tam sim no ceev yog xoom.Tom qab ntawd, qhov kev qhia ntawm magnetic induction vector yuav ua raws li hauv qab no:
Siv MATLAB program (MathWorks, Inc., USA) rau kev suav lej, ETU “LETI” daim ntawv tso cai kawm ntawv tus lej 40502181.
Raws li pom nyob rau hauv daim duab 7 Daim duab 8 Daim duab 9 Daim duab-10, lub zog hlau nplaum yog tsim los ntawm ib tug hlau nplaum oriented axially los ntawm qhov kawg ntawm lub tog raj kheej.Lub vojvoog zoo ntawm kev ua haujlwm yog sib npaug rau cov geometry ntawm cov hlau nplaum.Nyob rau hauv cylindrical hlau nplaum nrog ib lub tog raj kheej uas nws ntev yog ntau tshaj nws txoj kab uas hla, lub zog sib nqus teb yog pom nyob rau hauv lub axial-radial kev taw qhia (rau cov khoom sib txuas);Yog li ntawd, ib khub ntawm lub tog raj kheej nrog qhov sib piv loj dua (inch thiab ntev) MNP adsorption yog qhov zoo tshaj plaws.
Daim duab 7 Cov khoom siv sib nqus induction siv Bz raws Oz axis ntawm cov hlau nplaum;tus qauv loj ntawm cov hlau nplaum: dub kab 0.5 × 2mm, xiav kab 2 × 2mm, ntsuab kab 3 × 2mm, liab kab 5 × 2mm.
Daim duab 8 Qhov sib nqus induction Cheebtsam Br yog perpendicular rau cov hlau nplaum axis Oz;tus qauv loj ntawm cov hlau nplaum: dub kab 0.5 × 2mm, xiav kab 2 × 2mm, ntsuab kab 3 × 2mm, liab kab 5 × 2mm.
Daim duab 9 Qhov sib nqus induction siv Bz tivthaiv ntawm qhov deb r los ntawm qhov kawg axis ntawm cov hlau nplaum (z=0);tus qauv loj ntawm cov hlau nplaum: dub kab 0.5 × 2mm, xiav kab 2 × 2mm, ntsuab kab 3 × 2mm, liab kab 5 × 2mm.
Daim duab 10 Sib nqus induction tivthaiv raws cov kev taw qhia radial;Standard magnet loj: dub kab 0.5 × 2 hli, xiav kab 2 × 2 hli, ntsuab kab 3 × 2 hli, liab kab 5 × 2 hli.
Cov qauv tshwj xeeb hydrodynamic tuaj yeem siv los kawm txog cov qauv ntawm MNP xa mus rau cov qog nqaij hlav, mloog zoo rau nanoparticles hauv thaj chaw lub hom phiaj, thiab txiav txim siab tus cwj pwm ntawm nanoparticles nyob rau hauv hydrodynamic tej yam kev mob nyob rau hauv lub circulatory system.Cov hlau nplaum tas mus li tuaj yeem siv los ua cov hlau nplaum sab nraud.Yog tias peb tsis quav ntsej qhov kev sib cuam tshuam ntawm cov hlau nplaum ntawm cov nanoparticles thiab tsis xav txog cov qauv ntawm cov kua nplaum sib nqus, nws yog qhov txaus los kwv yees qhov kev cuam tshuam ntawm cov hlau nplaum thiab ib qho nanoparticles nrog ib qho kev kwv yees ntawm dipole-dipole.
Qhov twg m yog lub sij hawm sib nqus ntawm cov hlau nplaum, r yog lub vojvoog vector ntawm qhov chaw uas cov nanoparticle nyob, thiab k yog qhov system zoo.Hauv kev kwv yees dipole, thaj chaw ntawm cov hlau nplaum muaj qhov zoo sib xws (Daim duab 11).
Hauv ib qho chaw sib nqus sib nqus, cov nanoparticles tsuas yog tig raws cov kab ntawm lub zog.Nyob rau hauv ib qho kev sib nqus tsis sib xws, quab yuam ua rau nws:
Qhov twg yog qhov derivative ntawm ib qho kev taw qhia l.Tsis tas li ntawd, lub zog rub cov nanoparticles mus rau qhov tsis sib xws ntawm thaj chaw feem ntau, uas yog, qhov curvature thiab ntom ntawm cov kab ntawm lub zog nce.
Yog li ntawd, nws yog ntshaw kom siv ib tug txaus muaj zog hlau nplaum (los yog hlau nplaum saw) nrog pom tseeb axial anisotropy nyob rau hauv lub cheeb tsam uas hais nyob rau hauv.
Table 1 qhia txog lub peev xwm ntawm ib qho hlau nplaum uas yog qhov chaw sib nqus txaus los ntes thiab khaws MNP hauv lub txaj vascular ntawm daim ntawv thov teb.