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E kāohi i ka neʻe ʻana o nā nanoparticles iron oxide no ka hāʻawi ʻana i nā cytostatics
Mea kākau 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 Ke kikowaena noiʻi o ka Ministry of Health o ka Russian Federation, St. Petersburg, 197341, Russian Federation;2 St. Petersburg Electrotechnical University "LETI", St. Petersburg, 197376, Russian Federation;3 Center for Personalized Medicine, Almazov State Medical Research Center, Ministry of Health of the Russian Federation, St. Petersburg, 197341, Russia Federation;4FSBI "Influenza Research Institute i kapa ʻia ma hope o 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 Center, Ministry of Health of the Russian Federation, Saint-Petersburg, 197341, Russian Federation Tel +7 981 95264800 4997069 Email [email protected] Ka hope: ʻO kahi ala hoʻohiki i ka pilikia o ka cytostatic toxicity ka hoʻohana ʻana i nā nanoparticles magnetic (MNP) no ka lawe ʻana i ka lāʻau lapaʻau.Ke kumu: E hoʻohana i nā helu no ka hoʻoholo ʻana i nā hiʻohiʻona maikaʻi loa o ke kahua magnetic e hoʻomalu ai i nā MNPs in vivo, a e loiloi i ka pono o ka hāʻawi ʻana i ka magnetron o nā MNP i nā maʻi ʻiole i loko o ka vitro a me ka vivo.(MNPs-ICG) hoʻohana ʻia.Ua hana ʻia nā haʻawina ikaika o ka luminescence in vivo i nā ʻiole tumo, me ka ʻole a me ke kahua magnetic ma ke kahua o ka hoihoi.Ua hana ʻia kēia mau haʻawina ma kahi scaffold hydrodynamic i hoʻomohala ʻia e ka Institute of Experimental Medicine o ka Almazov State Medical Research Center o ka Russian Ministry of Health.Ka hopena: ʻO ka hoʻohana ʻana i nā magnet neodymium i hāpai i ka hōʻiliʻili koho o MNP.Hoʻokahi minuke ma hope o ka hoʻokele ʻana o MNPs-ICG i nā ʻiole e lawe ana i ka tumo, ʻo ka MNPs-ICG ka nui i hōʻiliʻili i loko o ke ake.I ka loaʻa ʻole a me ke alo o kahi māla magnetic, hōʻike kēia i kona ala metabolic.ʻOiai uaʻikeʻia ka piʻiʻana o ka fluorescence i loko o ka'ōpū ma ke alo o kahi māla magnetic,ʻaʻole i loli ka ikaika o ka fluorescence i ke ake o ka holoholona i ka manawa.Ka hopena: ʻO kēia ʻano MNP, i hui pū ʻia me ka ikaika o ke kahua magnetic i helu ʻia, hiki ke lilo i kumu no ka hoʻomohala ʻana i ka lawe ʻana i nā lāʻau cytostatic i hoʻopaʻa ʻia i nā ʻiʻo tumora.Hua'ōlelo: ka nānā 'ana i ka fluorescence, indocyanine, iron oxide nanoparticles, magnetron delivery of cytostatics, tumor targeting
ʻO nā maʻi tumor kekahi o nā kumu nui o ka make ma ka honua holoʻokoʻa.I ka manawa like, ke mau nei ka ikaika o ka hoʻonui ʻana i ka morbidity a me ka make ʻana o nā maʻi maʻi tumora.1 ʻO ka chemotherapy i hoʻohana ʻia i kēia lā kekahi o nā lāʻau lapaʻau nui no nā maʻi ʻokoʻa.I ka manawa like, pili mau ka hoʻomohala ʻana i nā ala e hōʻemi ai i ka ʻona o ka cytostatics.ʻO kahi ala hoʻohiki e hoʻoponopono ai i kāna pilikia ʻona, ʻo ia ka hoʻohana ʻana i nā mea lawe nano-scale e kuhikuhi i nā ala lawe lāʻau, hiki ke hāʻawi i ka hōʻiliʻili kūloko o nā lāʻau lapaʻau i loko o nā ʻiʻo tumora me ka hoʻonui ʻole ʻana i kā lākou hōʻiliʻili ʻana i nā kino olakino a me nā ʻiʻo.hoʻopaʻa ʻana.2 Hiki i kēia ʻano hana ke hoʻomaikaʻi i ka maikaʻi a me ka huli ʻana o nā lāʻau chemotherapeutic ma nā ʻiʻo ʻiʻo, ʻoiai e hōʻemi ana i kā lākou ʻona.
Ma waena o nā nanoparticles like ʻole i noʻonoʻo ʻia no ka hāʻawi ʻia ʻana o nā cytostatic agents, nā nanoparticles magnetic (MNPs) he mea hoihoi nui ma muli o kā lākou kemika kūikawā, biological, a me nā waiwai magnetic, e hōʻoiaʻiʻo ana i kā lākou versatility.No laila, hiki ke hoʻohana ʻia nā nanoparticles ma ke ʻano he ʻōnaehana hoʻomehana e mālama i nā ʻōpū me ka hyperthermia (magnetic hyperthermia).Hiki iā lākou ke hoʻohana ʻia ma ke ʻano he diagnostic agents (magnetic resonance diagnostic).3-5 Ke hoʻohana nei i kēia mau hiʻohiʻona, i hui pū ʻia me ka hiki ʻana o ka hōʻiliʻili MNP ma kahi kikoʻī, ma o ka hoʻohana ʻana i kahi kahua magnetic o waho, ʻo ka hāʻawi ʻana i nā hoʻomākaukau lāʻau lapaʻau i manaʻo ʻia e wehe i ka hana ʻana o kahi ʻōnaehana magnetron multifunctional e kuhikuhi i nā cytostatics i ka pūnaewele tumor. Nā Manaʻo.ʻO ia ʻōnaehana e hoʻokomo i ka MNP a me nā māla magnetic e hoʻomalu i ko lākou neʻe ʻana i ke kino.I kēia hihia, hiki ke hoʻohana ʻia nā māla magnetic waho a me nā implants i hoʻokomo ʻia i loko o ka ʻāpana o ke kino i loaʻa ka ʻōpū ma ke ʻano he kumu o ke kahua magnetic.6 He mau hemahema koʻikoʻi ka hana mua, me ka pono e hoʻohana i nā mea hana kūikawā no ka huli ʻana i nā lāʻau lapaʻau a me ka pono e hoʻomaʻamaʻa i nā limahana e hana i ke ʻoki.Eia kekahi, ua kaupalena ʻia kēia ʻano e ke kumu kūʻai kiʻekiʻe a kūpono wale no nā maʻi "superficial" kokoke i ka ʻili o ke kino.ʻO ke ala ʻē aʻe o ka hoʻohana ʻana i nā implants magnetic e hoʻonui i ke ʻano o ka hoʻohana ʻana i kēia ʻenehana, e hoʻomaʻamaʻa i kona hoʻohana ʻana i nā ʻōpū ma nā wahi like ʻole o ke kino.Hiki ke hoʻohana ʻia nā mea magnet a me nā magnet i hoʻohui ʻia i loko o ka stent intraluminal i mea kanu no ka hōʻino ʻana i ka maʻi maʻi i loko o nā ʻōpū hollow e hōʻoia i ko lākou patency.Eia naʻe, e like me kā mākou noiʻi ponoʻī ʻaʻole i paʻi ʻia, ʻaʻole lawa kēia mau mea e hōʻoia i ka paʻa ʻana o MNP mai ke kahe koko.
ʻO ka maikaʻi o ka lawe ʻana i ka lāʻau magnetron ma muli o nā kumu he nui: nā ʻano o ka mea lawe magnetic ponoʻī, a me nā hiʻohiʻona o ke kumu kumu magnetic (me nā ʻāpana geometric o nā magnet mau loa a me ka ikaika o ke kahua magnetic a lākou e hana ai).ʻO ka hoʻomohala ʻana i ka ʻenehana hoʻopuka paʻa kelepona alakaʻi kūleʻa e pono e komo i ka hoʻomohala ʻana i nā mea lawe lāʻau lāʻau nanoscale magnetic kūpono, e loiloi ana i ko lākou palekana, a me ka hoʻomohala ʻana i kahi protocol visualization e hiki ai ke nānā i kā lākou neʻe ʻana i ke kino.
Ma kēia haʻawina, helu makemakika mākou i nā hiʻohiʻona mākaʻikaʻi maikaʻi loa e hoʻomalu i ka mea lawe lāʻau lāʻau nano-scale i loko o ke kino.Ua aʻo pū ʻia ka hiki ke hoʻopaʻa ʻia ka MNP ma o ka pā kīʻaha koko ma lalo o ka mana o kahi kahua magnetic i hoʻopili ʻia me kēia mau hiʻohiʻona helu helu i loko o nā kīʻaha koko ʻiole kaʻawale.Eia kekahi, ua hoʻohui mākou i nā conjugates o MNPs a me nā mea hana fluorescent a hoʻomohala i kahi protocol no kā lākou ʻike ʻana i vivo.Ma lalo o nā kūlana vivo, i loko o nā ʻiole hoʻohālike tumora, ua aʻo ʻia ka hōʻiliʻili ʻana o nā MNP i loko o nā ʻiʻo tumo i ka wā i lawelawe ʻia ma lalo o ka mana o kahi kahua magnetic.
I loko o ka haʻawina in vitro, ua hoʻohana mākou i ka MNP kuhikuhi, a ma ka noiʻi in vivo, ua hoʻohana mākou i ka MNP i uhi ʻia me ka lactic acid polyester (polylactic acid, PLA) i loaʻa i kahi mea fluorescent (indolecyanine; ICG).Hoʻokomoʻia ka MNP-ICG i loko I ka hihia, hoʻohana (MNP-PLA-EDA-ICG).
Ua wehewehe ʻia ka synthesis a me ke kino a me ke kemika o MNP ma nā wahi ʻē aʻe.7,8
No ka synthesize MNPs-ICG, ua hana mua ʻia nā conjugates PLA-ICG.Ua hoʻohana ʻia ka hui ʻana o ka pauka racemic o PLA-D a me PLA-L me ke kaumaha molekala o 60 kDa.
No ka mea, ʻo ka PLA a me ka ICG nā waikawa ʻelua, i mea e hoʻohui ai i nā conjugates PLA-ICG, pono mua e synthesize i kahi spacer i hoʻopau ʻia ma PLA, e kōkua iā ICG chemisorb i ka spacer.Hoʻopili ʻia ka spacer me ka hoʻohana ʻana i ka ethylene diamine (EDA), ke ʻano carbodiimide a me ka carbodiimide hiki ke hoʻoheheʻe ʻia i ka wai, 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDAC).Hoʻopili ʻia ka spacer PLA-EDA penei.Hoʻohui i 20-fold molar oi o EDA a me 20-fold molar oi o EDAC i 2 mL o 0.1 g/mL PLA chloroform solution.Ua lawe ʻia ka synthesis i loko o kahi pahu hoʻāʻo polypropylene 15 mL ma kahi shaker ma ka wikiwiki o 300 min-1 no 2 mau hola.Hōʻike ʻia ka hoʻolālā synthesis ma ke Kiʻi 1. E hana hou i ka synthesis me kahi 200-fold o nā reagents e hoʻonui i ka hoʻolālā synthesis.
I ka pau ʻana o ka synthesis, ua centrifuged ka hopena i ka wikiwiki o 3000 min-1 no 5 mau minuke e wehe i nā derivatives polyethylene precipitated.A laila, 2 mL o ka 0.5 mg/mL ICG solution i dimethyl sulfoxide (DMSO) i hoʻohui ʻia i ka 2 mL solution.Hoʻopaʻa ʻia ka mea hoʻouluulu i ka wikiwiki o 300 min-1 no 2 mau hola.Hōʻike ʻia ke kiʻikuhi schematic o ka conjugate i loaʻa ma ke Kiʻi 2.
Ma 200 mg MNP, ua hoʻohui mākou i 4 mL PLA-EDA-ICG conjugate.E hoʻohana i ka lulu LS-220 (LOIP, Rusia) e hoʻoulu i ka hoʻomaha no 30 mau minuke ma ke alapine o 300 min-1.A laila, holoi ʻia me ka isopropanol ʻekolu manawa a hoʻokaʻawale ʻia ka magnetic.E hoʻohana i ka UZD-2 Ultrasonic Disperser (FSUE NII TVCH, Russia) e hoʻohui i ka IPA i ka hoʻokuʻu ʻana no 5-10 mau minuke ma lalo o ka hana ultrasonic mau.Ma hope o ke kolu o ka holoi ʻana i ka IPA, ua holoi ʻia ka wai me ka wai i hoʻopaʻa ʻia a hoʻokuʻu hou ʻia i loko o ka paʻakai physiological ma kahi ʻano o 2 mg / mL.
Ua hoʻohana ʻia nā mea hana ZetaSizer Ultra (Malvern Instruments, UK) e aʻo i ka puʻunaue nui o ka MNP i loaʻa i ka wai wai.Ua hoʻohana ʻia kahi microscope electron transmission (TEM) me ka JEM-1400 STEM field emission cathode (JEOL, Iapana) e aʻo i ke ʻano a me ka nui o ka MNP.
I loko o kēia haʻawina, hoʻohana mākou i nā mea magnet cylindrical mau loa (N35 grade; me ka uhi pale nickel) a me nā nui maʻamau (lōʻihi axis lōʻihi × cylinder diameter): 0.5 × 2 mm, 2 × 2 mm, 3 × 2 mm a me 5 × 2. mm.
ʻO ka noiʻi in vitro o ka lawe ʻana i ka MNP i ka ʻōnaehana hoʻohālike i hana ʻia ma kahi scaffold hydrodynamic i hoʻomohala ʻia e ka Institute of Experimental Medicine o ka Almazov State Medical Research Center o ke Kuhina Ola o Rūsia.He 225 mL ka nui o ka wai kahe (wai distilled a i ʻole Krebs-Henseleit solution).Hoʻohana ʻia nā magnetized cylindrical axially magnetized e like me nā magnet mau loa.E kau i ka magnet ma luna o kahi paʻa 1.5 mm ka mamao mai ka paia o loko o ka ipu aniani waena, me kona hopena e kū pono ana i ka ʻaoʻao o ka paipu (kū pololei).ʻO ke kahe o ka wai i loko o ka loop pani ʻia ʻo 60 L / h (e pili ana i ka wikiwiki laina o 0.225 m / s).Hoʻohana ʻia ʻo Krebs-Henseleit solution ma ke ʻano he wai kahe no ka mea he analog ia o ka plasma.ʻO ka coefficient viscosity dynamic o ka plasma he 1.1-1.3 mPa∙s.9 Hoʻoholo ʻia ka nui o ka MNP i hoʻopaʻa ʻia i loko o ke kahua magnetic e ka spectrophotometry mai ka hoʻopaʻa ʻana o ka hao i loko o ka wai kahe ma hope o ka hoʻokolohua.
Eia kekahi, ua hoʻokō ʻia nā haʻawina hoʻokolohua ma luna o kahi papa mechanics wai i hoʻomaikaʻi ʻia e hoʻoholo ai i ka pili pili o nā kīʻaha koko.Hōʻike ʻia nā mea nui o ke kākoʻo hydrodynamic ma ke Kiʻi 3. ʻO nā mea nui o ka stent hydrodynamic he puka pani e hoʻohālikelike ana i ka ʻāpana keʻa o ka ʻōnaehana vascular model a me kahi pahu mālama.Hāʻawi ʻia ka neʻe ʻana o ka wai hoʻohālike ma ka ʻaoʻao o ka module moku koko e kahi pamu peristaltic.I ka wā o ka hoʻokolohua, mālama i ka vaporization a me ke ʻano wela e pono ai, a nānā i nā ʻōnaehana ʻōnaehana (ka wela, ke kaomi, ka kahe wai, a me ka waiwai pH).
Kiʻi 3 Block diagram o ka hoʻonohonoho i hoʻohana ʻia no ke aʻo ʻana i ka permeability o ka pā aʻa carotid.1-wai pahu, 2-peristaltic pamu, 3-mechanism no ka hoʻokomo 'ana i ka hoʻokuʻu 'ia i loaʻa ka MNP i loko o ka loop, 4-kahe mika, 5-pemi 'ana i loko o ka loop, 6-heat exchanger, 7-keena me ka ipu , 8-ke kumu. o ke kahua magnetic, 9-ka baluna me ka hydrocarbons.
ʻO ke keʻena i loko o ka pahu he ʻekolu pahu: kahi pahu nui i waho a me ʻelua pahu liʻiliʻi, kahi e hele ai nā lima o ke kaapuni waena.Hoʻokomo ʻia ka puʻu i loko o ka ipu liʻiliʻi, ua kaula ʻia ka ipu ma luna o ka ipu liʻiliʻi, a ua nakinaki ʻia ka wēlau o ka cannula me kahi uwea lahilahi.ʻO ka hakahaka ma waena o ka pahu nui a me ka pahu liʻiliʻi e hoʻopihaʻia me ka wai i hoʻomaʻemaʻeʻia, a ua mau ka mahana ma muli o ka piliʻana i ka mea hoʻololi wela.Hoʻopiha ʻia ka wahi i loko o ka pahu liʻiliʻi me ka hoʻonā Krebs-Henseleit e mālama i ke ola o nā ʻāpana koko.Hoʻopiha pū ʻia ka pahu me ka hoʻonā Krebs-Henseleit.Hoʻohana ʻia ka ʻōnaehana hoʻolako kinoea (carbon) e hoʻopau i ka hopena i loko o ka pahu liʻiliʻi i loko o ka pahu waihona a me ke keʻena i loko o ka ipu (Figure 4).
Kiʻi 4 ʻO ke keʻena kahi i waiho ʻia ai ka ipu.1-Canula no ka hoʻohaʻahaʻa ʻana i nā kīʻaha koko, 2-Keena waho, 3-Keʻena liʻiliʻi.Hōʻike ka pua i ke kuhikuhi o ka wai hoʻohālike.
No ka hoʻoholo ʻana i ka index permeability pili o ka pā moku, ua hoʻohana ʻia ke aʻa carotid iole.
ʻO ka hoʻokomo ʻana o ka MNP suspension (0.5mL) i loko o ka ʻōnaehana i kēia mau hiʻohiʻona: ʻo ka nui o loko o ka pahu a me ka paipu hoʻohui i ka loop he 20mL, a ʻo ka leo kūloko o kēlā me kēia keʻena he 120mL.ʻO ke kumu kahua magnetic waho he magnet mau loa me ka nui maʻamau o 2 × 3 mm.Hoʻonoho ʻia ma luna o kekahi o nā keʻena liʻiliʻi, 1 knm ka mamao mai ka pahu, me kekahi hopena e kū pono ana i ka paia pahu.Mālama ʻia ka mahana ma 37 ° C.Hoʻonohonoho ʻia ka mana o ka paila wili i 50%, e like me ka wikiwiki o 17 cm / s.Ma ke ʻano he mana, ua lawe ʻia nā laʻana i loko o kahi keena me ka ʻole o nā magnet mau loa.
Hoʻokahi hola ma hope o ka hoʻokō ʻana i kahi ʻike i hāʻawi ʻia o MNP, ua lawe ʻia kahi hāpana wai mai ke keʻena.Ua ana ʻia ka ʻāpana ʻāpana e kahi spectrophotometer me ka hoʻohana ʻana i ka spectrophotometer Unico 2802S UV-Vis (United Products & Instruments, USA).No ka noʻonoʻo ʻana i ka spectrum absorption o ka hoʻokuʻu ʻana o MNP, ua hana ʻia ke ana ma 450 nm.
Wahi a nā alakaʻi alakaʻi ʻo Rus-LASA-FELASA, hānai ʻia nā holoholona āpau a hānai ʻia i nā keʻena pathogen-free.Hoʻopili kēia haʻawina i nā kānāwai kūpono kūpono no nā hoʻokolohua holoholona a me ka noiʻi, a ua loaʻa iā ia ka ʻae kūpono mai ka Almazov National Medical Research Center (IACUC).Ua inu nā holoholona i ka wai ad libitum a hānai mau.
Ua mālama ʻia ke aʻo ʻana ma 10 anesthetized 12-week-old male immunodeficient NSG mice (NOD.Cg-Prkdcscid Il2rgtm1Wjl/Szj, Jackson Laboratory, USA) 10, ke kaupaona ʻana 22 g ± 10%.Ma muli o ka hoʻopaʻa ʻia ʻana o nā ʻiole immunodeficiency, ʻae nā ʻiole immunodeficiency o kēia laina i ka hoʻololi ʻana o nā pūnaewele kanaka a me nā ʻiʻo me ka hōʻole ʻole ʻia.ʻO nā hoa littermates mai nā hīnaʻi like ʻole i hāʻawi ʻia i ka hui hoʻokolohua, a ua hui pū ʻia a ʻike ʻia paha lākou i ka moena o nā hui ʻē aʻe e hōʻoia i ka ʻike like ʻana i ka microbiota maʻamau.
Hoʻohana ʻia ka laina cell cancer HeLa no ka hoʻokumu ʻana i kahi kumu hoʻohālike xenograft.Hoʻoulu ʻia nā cell i DMEM i loaʻa ka glutamine (PanEco, Russia), hoʻohui ʻia me 10% fetal bovine serum (Hyclone, USA), 100 CFU/mL penicillin, a me 100 μg/mL streptomycin.Hāʻawi ʻia ka laina kelepona e ka Gene Expression Regulation Laboratory o ka Institute of Cell Research o ka Russian Academy of Science.Ma mua o ka hoʻokomo ʻia ʻana, ua wehe ʻia nā pūnaewele HeLa mai ka plastic moʻomeheu me kahi 1:1 trypsin: Versene solution (Biolot, Russia).Ma hope o ka holoiʻana, ua hoʻokuʻuʻia nā pūnaewele i loko o ke kikowaena piha i ka 5 × 106 pūnaewele no 200 μL, a hoʻoheheʻeʻia me ka matrix membrane basement (LDEV-FREE, MATRIGEL® CORNING®) (1: 1, ma ka hau).ʻO ka hoʻopaʻa ʻana o ke kelepona i hoʻomākaukau ʻia ua hoʻokomo ʻia ma lalo o ka ʻili o ka ʻūhā ʻiole.E hoʻohana i nā calipers uila e nānā i ka ulu ʻana o ka maʻi maʻi i kēlā me kēia 3 lā.
I ka hiki ʻana o ke koko i 500 mm3, ua hoʻokomo ʻia kahi magnet mau i loko o ka ʻiʻo ʻiʻo o ka holoholona hoʻokolohua kokoke i ka ʻōpū.I loko o ka hui hoʻokolohua (MNPs-ICG + tumor-M), 0.1 mL o ka hoʻokuʻu ʻana o MNP i hoʻopaʻa ʻia a hōʻike ʻia i kahi kahua magnetic.Ua hoʻohana ʻia nā holoholona holoʻokoʻa i mālama ʻole ʻia ma ke ʻano he hoʻomalu (hopena).Eia hou, ua hoʻohanaʻia nā holoholona i hoʻokomoʻia me 0.1 mL o MNP akāʻaʻole i hoʻokomoʻia me nā magnets (MNPs-ICG + tumor-BM).
Ua hana ʻia ka ʻike fluorescence o in vivo a me in vitro laʻana ma ka IVIS Lumina LT series III bioimager (PerkinElmer Inc., USA).No ka ʻike in vitro, ua hoʻohui ʻia kahi leo o 1 mL o synthetic PLA-EDA-ICG a me MNP-PLA-EDA-ICG conjugate i nā pūnāwai pā.I ka noʻonoʻo ʻana i nā hiʻohiʻona fluorescence o ka dye ICG, ua koho ʻia ka kānana maikaʻi loa e hoʻoholo ai i ka ikaika o ka luminous o ka hāpana: ʻo ka lōʻihi o ka hawewe excitation ʻo 745 nm, a ʻo 815 nm ka lōʻihi o ka hawewe.Ua hoʻohana ʻia ka polokalamu Living Image 4.5.5 (PerkinElmer Inc.) no ke ana ʻana i ka ikaika o ka fluorescence o nā pūnāwai i loko o ka conjugate.
ʻO ka ikaika o ka fluorescence a me ka hōʻiliʻili ʻana o ka conjugate MNP-PLA-EDA-ICG ua ana ʻia i loko o ka vivo tumor model mice, me ka ʻole o ka hele ʻana a me ka hoʻohana ʻana i kahi kahua magnetic ma kahi o ka hoihoi.Ua hoʻomaʻamaʻa ʻia nā ʻiole me ka isoflurane, a laila ua hoʻokomo ʻia ka 0.1 mL o ka conjugate MNP-PLA-EDA-ICG ma o ka vein huelo.Ua hoʻohana ʻia nā ʻiole i mālama ʻole ʻia ma ke ʻano he mana maikaʻi ʻole no ka loaʻa ʻana o kahi kāʻei fluorescent.Ma hope o ka lawelawe ʻana i ka conjugate intravenously, e kau i ka holoholona ma kahi pae wela (37°C) i loko o ke keʻena o ka IVIS Lumina LT series III fluorescence imager (PerkinElmer Inc.) ʻoiai e mālama ana i ka inhalation me 2% isoflurane anaesthetization.E hoʻohana i ka kānana i kūkulu ʻia i loko o ICG (745–815 nm) no ka ʻike ʻana i ka hōʻailona 1 minuke a me 15 mau minuke ma hope o ka hoʻokomo ʻana o MNP.
No ka loiloi i ka hōʻiliʻili ʻana o ka conjugate i loko o ka ʻōpū, ua uhi ʻia ka ʻāpana peritoneal o ka holoholona me ka pepa, kahi i hiki ai ke hoʻopau i ka fluorescence mālamalama e pili ana i ka hōʻiliʻili ʻana o nā ʻāpana i loko o ke ake.Ma hope o ke aʻo ʻana i ka biodistribution o MNP-PLA-EDA-ICG, ua hoʻokaʻawale ʻia nā holoholona e ka overdose o ka isoflurane anesthesia no ka hoʻokaʻawale ʻana o nā wahi tumo a me ka loiloi nui o ka radiation fluorescence.E hoʻohana i ka lako polokalamu Living Image 4.5.5 (PerkinElmer Inc.) no ka hoʻoponopono lima ʻana i ka hōʻailona hōʻailona mai ka ʻāpana hoihoi i koho ʻia.Ua lawe ʻia ʻekolu ana no kēlā me kēia holoholona (n = 9).
Ma kēia haʻawina, ʻaʻole mākou i helu i ka hoʻouka kūleʻa o ICG ma MNPs-ICG.Eia hou,ʻaʻole mākou i hoʻohālikelike i ka pono o ka mālamaʻana i nā nanoparticles ma lalo o ka mana o nā magnet mau o nāʻano likeʻole.Eia kekahi, ʻaʻole mākou i loiloi i ka hopena lōʻihi o ka māla magnetic i ka paʻa ʻana o nā nanoparticles i nā ʻiʻo tumora.
ʻO nā nanoparticles ka mana, me ka nui awelika o 195.4 nm.Eia kekahi, ua loaʻa i ka hoʻokuʻu ʻia nā agglomerates me ka nui awelika o 1176.0 nm (Figure 5A).Ma hope mai, ua kānana ʻia ka ʻāpana ma o kahi kānana centrifugal.ʻO ka mana zeta o nā ʻāpana he -15.69 mV (Figure 5B).
Kiʻi 5 ʻO nā waiwai kino o ka hoʻokuʻu ʻia: (A) ka māhele ʻana i ka nui o nā ʻāpana;(B) ka hāʻawi ʻana i nā ʻāpana i ka hiki ke zeta;(C) kiʻi TEM o nā nanoparticles.
ʻO 200 nm (Figure 5C) ka nui o ka nui, i haku ʻia me kahi MNP hoʻokahi me ka nui o 20 nm, a me kahi pūpū organik conjugated PLA-EDA-ICG me kahi haʻahaʻa electron haʻahaʻa.Hiki ke wehewehe ʻia ka hoʻokumu ʻana o nā agglomerates i loko o nā wai wai e ka modulus haʻahaʻa haʻahaʻa o ka ikaika electromotive o kēlā me kēia nanoparticles.
No nā mākēneki mau, i ka wā i hoʻopaʻa ʻia ai ka magnetization i ka leo V, ua māhele ʻia ka ʻōlelo hoʻohui i ʻelua mau mea hoʻohui, ʻo ia ka leo a me ka ʻili:
I ka hihia o kahi laʻana me ka magnetization mau, ʻo ka nui o kēia manawa he zero.A laila, e lawe ka ʻōlelo o ka vector induction magnetic i kēia ʻano:
E hoʻohana i ka polokalamu MATLAB (MathWorks, Inc., USA) no ka helu helu, ETU "LETI" helu laikini hoʻonaʻauao 40502181.
E like me ka mea i hōʻike ʻia ma ka Figure 7 Figure 8 Figure 9 Figure-10, ua hoʻokumu ʻia ka māla ikaika loa e kahi magnet oriented axially mai ka hopena o ka cylinder.ʻO ka radius kūpono o ka hana e like me ka geometry o ka magnet.I loko o ka cylindrical magnets me ka cylinder nona ka lōʻihi i ʻoi aku ka nui ma mua o kona anawaena, ʻike ʻia ka māla ikaika loa ma ke kuhikuhi axial-radial (no ka mea pili);no laila, ʻo kahi pālua o nā cylinders me kahi lākiō hiʻohiʻona nui (ka anawaena a me ka lōʻihi) ʻo MNP adsorption ka mea maikaʻi loa.
Fig. 7 ʻO ka ʻāpana o ka ikaika induction magnetic Bz ma ke axis Oz o ka magnet;ka nui maʻamau o ka magnet: laina ʻeleʻele 0.5 × 2mm, laina polū 2 × 2mm, laina ʻōmaʻomaʻo 3 × 2mm, laina ʻulaʻula 5 × 2mm.
Kiʻi 8 ʻO ka ʻāpana induction magnetic Br ua kū pololei i ka axis magnet Oz;ka nui maʻamau o ka magnet: laina ʻeleʻele 0.5 × 2mm, laina polū 2 × 2mm, laina ʻōmaʻomaʻo 3 × 2mm, laina ʻulaʻula 5 × 2mm.
Kiʻi 9 ʻO ka mea Bz induction induction ikaika ma ka mamao r mai ke koʻi hope o ka magnet (z=0);ka nui maʻamau o ka magnet: laina ʻeleʻele 0.5 × 2mm, laina polū 2 × 2mm, laina ʻōmaʻomaʻo 3 × 2mm, laina ʻulaʻula 5 × 2mm.
Kiʻi 10 Mea hoʻokomo magnetika ma ka ʻaoʻao radial;ka nui magnet maʻamau: laina ʻeleʻele 0.5 × 2mm, laina polū 2 × 2mm, laina ʻōmaʻomaʻo 3 × 2mm, laina ʻulaʻula 5 × 2mm.
Hiki ke hoʻohana ʻia nā hiʻohiʻona hydrodynamic kūikawā no ke aʻo ʻana i ke ʻano o ka hāʻawi ʻana i ka MNP i nā ʻiʻo tumo, hoʻopaʻa i nā nanoparticles i ka wahi i hoʻopaʻa ʻia, a hoʻoholo i ka ʻano o nā nanoparticles ma lalo o nā kūlana hydrodynamic i ka ʻōnaehana circulatory.Hiki ke hoʻohana ʻia nā magnet paʻa e like me nā māla magnetic waho.Inā mākou e haʻalele i ka pilina magnetostatic ma waena o nā nanoparticles a ʻaʻole e noʻonoʻo i ke kumu hoʻohālike o ka wai magnetic, ua lawa ia e koho i ka pilina ma waena o ka magnet a me kahi nanoparticle me kahi hoʻohālikelike dipole-dipole.
Ma kahi o ka m ka manawa mākēneki o ka magnet, ʻo r ka radius vector o ke kiko kahi i loaʻa ai ka nanoparticle, a ʻo k ke kumu kumu.Ma ka hoʻohālikelike dipole, loaʻa i ke kahua o ka magnet kahi hoʻonohonoho like (Figure 11).
I loko o ke kahua mākēneki like ʻole, ʻōwili wale nā ​​nanoparticles ma nā laina o ka ikaika.I loko o kahi mānoanoa like ʻole, hana ka ikaika ma luna o ia:
Aia i hea ka huahelu o kahi kuhikuhi l.Eia kekahi, huki ka ikaika i nā nanoparticles i loko o nā wahi like ʻole o ke kula, ʻo ia hoʻi, ka piʻi ʻana o ka curvature a me ka nui o nā laina o ka ikaika.
No laila, makemake ʻia ka hoʻohana ʻana i kahi magnet ikaika (a i ʻole kaulahao magnet) me ka anisotropy axial maopopo ma kahi o nā ʻāpana.
Hōʻike ka Papa 1 i ka hiki ke hoʻohana i hoʻokahi magnet ma ke ʻano he kumu māla magnetic kūpono e hopu a mālama i ka MNP ma ka moena vascular o ke kahua noi.