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E kāohi i ka neʻe ʻana o nā nanoparticles hao oxide magnetic no ka lawe ʻana i nā cytostatics i kuhikuhi ʻia
Mea kākau Toropova Y, Korolev D, Istomina M, Shulmeyster G, Petukhov A, Mishanin V, Gorshkov A, Podyacheva E, Gareev K, Bagrov A, Demidov O
ʻO 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 Ke Kikowaena Noiʻi Lapaʻau Lahui o ke Kuhina Ola o ka Russian Federation, St. Petersburg, 197341, Russian Federation; 2 Ke Kulanui Electrotechnical ʻo St. Petersburg "LETI", St. Petersburg, 197376, Russian Federation; 3 Ke Kikowaena no ka Lāʻau Lapaʻau Pilikino, 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 Kamaʻilio: Yana ToropovaAlmazov National Medical Research Centre, Ministry of Health of the Russian Federation, Saint-Petersburg, 197341, Russian Federation Kelepona +7 981 95264800 4997069 Leka uila [email protected] Ka Moolelo: ʻO kahi ala hoʻohiki i ka pilikia o ka ʻawahia cytostatic ʻo ia ka hoʻohana ʻana i nā nanoparticles magnetic (MNP) no ka lawe ʻana i ka lāʻau i kuhikuhi ʻia. Pahuhopu: E hoʻohana i nā helu e hoʻoholo ai i nā ʻano maikaʻi loa o ke kahua magnetic e kāohi ana i nā MNP i vivo, a e loiloi i ka pono o ka lawe ʻana o ka magnetron o nā MNP i nā ʻiole tumors in vitro a in vivo. Hoʻohana ʻia (MNPs-ICG). Ua hana ʻia nā haʻawina ikaika luminescence in vivo i nā ʻiole tumor, me a me ka ʻole o kahi kahua magnetic ma kahi hoihoi. Ua hoʻokō ʻia kēia mau haʻawina ma kahi scaffold hydrodynamic i hoʻomohala ʻia e ka Institute of Experimental Medicine o ke Almazov State Medical Research Center o ke Kuhina Ola o Rūsia. Hopena: ʻO ka hoʻohana ʻana i nā magnet neodymium i hoʻolaha i ka hōʻiliʻili koho o MNP. Hoʻokahi minuke ma hope o ka lawelawe ʻana o MNPs-ICG i nā ʻiole e lawe ana i ka tumor, hōʻiliʻili nui ʻo MNPs-ICG i loko o ke ake. I ka loaʻa ʻole a me ke alo o kahi kahua magnetic, hōʻike kēia i kona ala metabolic. ʻOiai ua ʻike ʻia ka hoʻonui ʻia o ka fluorescence i loko o ka tumor i ke alo o kahi kahua magnetic, ʻaʻole i loli ka ikaika fluorescence i loko o ke ake o ka holoholona i ka hala ʻana o ka manawa. 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 o nā lāʻau cytostatic i kāohi ʻia e ka magnetic i nā ʻiʻo tumor. Nā huaʻōlelo koʻikoʻi: ka nānā ʻana o ka fluorescence, indocyanine, nanoparticles hao oxide, ka lawe ʻana o ka magnetron o cytostatics, tumor targeting
ʻO nā maʻi puʻupuʻu kekahi o nā kumu nui o ka make ma ka honua holoʻokoʻa. I ka manawa like, ke mau nei ka dinamika o ka hoʻonui ʻia ʻana o ka maʻi a me ka make ʻana o nā maʻi puʻupuʻu. 1 ʻO ka chemotherapy i hoʻohana ʻia i kēia lā kekahi o nā lāʻau lapaʻau nui no nā puʻupuʻu like ʻole. I ka manawa like, pili mau ka hoʻomohala ʻana i nā ʻano hana e hōʻemi ai i ka ʻona ʻōnaehana o nā cytostatics. ʻO kahi ʻano hana hoʻohiki e hoʻoponopono ai i kāna pilikia ʻona, ʻo ia ka hoʻohana ʻana i nā mea lawe nano-scale e kuhikuhi i nā ʻano lawe lāʻau, hiki ke hāʻawi i ka hōʻiliʻili kūloko o nā lāʻau lapaʻau i loko o nā ʻiʻo puʻupuʻu me ka ʻole o ka hoʻonui ʻana i kā lākou hōʻiliʻili ʻana i loko o nā kino a me nā ʻiʻo olakino. 2 Hiki i kēia ʻano hana ke hoʻomaikaʻi i ka pono a me ka kuhikuhi ʻana o nā lāʻau chemotherapeutic ma nā ʻiʻo puʻupuʻu, me ka hoʻemi ʻana i ko lākou ʻona ʻōnaehana.
Ma waena o nā nanoparticles like ʻole i manaʻo ʻia no ka lawe ʻana i nā mea cytostatic i kuhikuhi ʻia, ʻo nā nanoparticles magnetic (MNPs) he mea hoihoi loa ia ma muli o kā lākou mau waiwai kemika, olaola, a me ka magnetic kū hoʻokahi, e hōʻoiaʻiʻo ana i ko lākou versatility. No laila, hiki ke hoʻohana ʻia nā nanoparticles magnetic ma ke ʻano he ʻōnaehana hoʻomehana e mālama i nā tumors me ka hyperthermia (magnetic hyperthermia). Hiki ke hoʻohana ʻia lākou ma ke ʻano he mau mea diagnostic (magnetic resonance diagnosis). 3-5 Ke hoʻohana nei i kēia mau ʻano, i hui pū ʻia me ka hiki ke hōʻiliʻili ʻia ʻo MNP ma kahi kikoʻī, ma o ka hoʻohana ʻana i kahi kahua magnetic waho, ʻo ka lawe ʻana i nā hoʻomākaukau lāʻau lapaʻau i kuhikuhi ʻia e wehe i ka hoʻokumu ʻana o kahi ʻōnaehana magnetron multifunctional e kuhikuhi i nā cytostatics i ka pūnaewele tumor Prospects. ʻO ia ʻōnaehana e komo pū me MNP a me nā kahua magnetic e kāohi i ko lākou neʻe ʻana i loko o ke kino. I kēia hihia, hiki ke hoʻohana ʻia nā kahua magnetic waho a me nā implants magnetic i kau ʻia ma kahi o ke kino e loaʻa ana ka tumor ma ke ʻano he kumu o ke kahua magnetic. 6 He mau hemahema koʻikoʻi ke ʻano mua, me ka pono e hoʻohana i nā lako hana kūikawā no ka hoʻolālā magnetic o nā lāʻau lapaʻau a me ka pono e hoʻomaʻamaʻa i nā limahana e hana i ke ʻoki kino. Eia kekahi, ua kaupalena ʻia kēia ʻano hana e ke kumukūʻai kiʻekiʻe a kūpono wale nō ia no nā puʻupuʻu "surficial" kokoke i ka ʻili o ke kino. ʻO ke ʻano ʻē aʻe o ka hoʻohana ʻana i nā implants magnetic e hoʻonui i ka laulā o ka hoʻohana ʻana o kēia ʻenehana, e hoʻomaʻamaʻa ana i kona hoʻohana ʻana ma nā puʻupuʻu i loaʻa ma nā ʻāpana like ʻole o ke kino. Hiki ke hoʻohana ʻia nā magnet pākahi a me nā magnet i hoʻohui ʻia i loko o ka stent intraluminal ma ke ʻano he implants no ka hōʻino ʻana o ka puʻupuʻu i nā ʻōpū hakahaka e hōʻoia i ko lākou patency. Eia nō naʻe, e like me kā mākou noiʻi ponoʻī i paʻi ʻole ʻia, ʻaʻole lawa ka magnetic e hōʻoia i ka paʻa ʻana o MNP mai ke kahe koko.
ʻO ka pono o ka lawe ʻana o ka lāʻau magnetron e pili ana i nā kumu he nui: nā ʻano o ka mea lawe magnetic ponoʻī, a me nā ʻano o ke kumu kahua magnetic (me nā ʻano geometric o nā magnet mau a me ka ikaika o ke kahua magnetic a lākou e hana ai). ʻO ka hoʻomohala ʻana i ka ʻenehana lawe ʻana o ka mea hoʻōki cell alakaʻi magnetic pono e pili i ka hoʻomohala ʻana i nā mea lawe lāʻau nanoscale magnetic kūpono, ka loiloi ʻana i ko lākou palekana, a me ka hoʻomohala ʻana i kahi protocol visualization e hiki ai ke hahai i kā lākou neʻe ʻana i loko o ke kino.
Ma kēia haʻawina, ua helu mākou ma ke ʻano makemakika i nā ʻano kahua magnetic kūpono e kāohi i ka mea lawe lāʻau nano-scale magnetic i loko o ke kino. Ua aʻo ʻia hoʻi ka hiki ke hoʻopaʻa i ka MNP ma o ka paia o ke kīʻaha koko ma lalo o ka mana o kahi kahua magnetic i hoʻopili ʻia me kēia mau ʻano computational i loko o nā kīʻaha koko ʻiole i hoʻokaʻawale ʻia. Eia kekahi, ua synthesize mākou i nā conjugates o MNPs a me nā mea fluorescent a hoʻomohala i kahi protocol no kā lākou visualization in vivo. Ma lalo o nā kūlana in vivo, i loko o nā ʻiole hoʻohālike tumor, ua aʻo ʻia ka pono o ka hōʻiliʻili ʻana o MNPs i loko o nā ʻiʻo tumor i ka wā e lawelawe ʻia ai ma ke ʻano ʻōnaehana ma lalo o ka mana o kahi kahua magnetic.
Ma ke aʻo ʻana in vitro, ua hoʻohana mākou i ka MNP kuhikuhi, a ma ke aʻo ʻana in vivo, ua hoʻohana mākou i ka MNP i uhi ʻia me ka polyester lactic acid (polylactic acid, PLA) e loaʻa ana kahi mea fluorescent (indolecyanine; ICG). Hoʻokomo ʻia ʻo MNP-ICG i loko o ka hihia, hoʻohana (MNP-PLA-EDA-ICG).
Ua wehewehe kikoʻī ʻia ka synthesis a me nā waiwai kino a me ke kemika o MNP ma kahi ʻē aʻe. 7,8
I mea e hana ai i nā MNPs-ICG, ua hana mua ʻia nā hui PLA-ICG. Ua hoʻohana ʻia kahi hui pauka racemic o PLA-D a me PLA-L me ke kaumaha molekala o 60 kDa.
ʻOiai he mau waikawa ʻelua ʻo PLA a me ICG, i mea e hana ai i nā hui PLA-ICG, pono mua e hana i kahi spacer amino-terminated ma PLA, kahi e kōkua ai i ka ICG chemisorb i ka spacer. Ua hana ʻia ka spacer me ka hoʻohana ʻana i ka ethylene diamine (EDA), ke ʻano carbodiimide a me ka carbodiimide wai-soluble, 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDAC). Ua hana ʻia ka spacer PLA-EDA penei. E hoʻohui i ka 20-fold molar excess o EDA a me 20-fold molar excess o EDAC i 2 mL o 0.1 g/mL PLA chloroform solution. Ua hana ʻia ka hana ʻana i loko o kahi paipu hoʻāʻo polypropylene 15 mL ma kahi shaker ma ka wikiwiki o 300 min-1 no 2 mau hola. Hōʻike ʻia ke ʻano hana hana ma ke Kiʻi 1. E hana hou i ka hana ʻana me kahi 200-fold excess o nā reagents e hoʻomaikaʻi i ka ʻano hana hana.
I ka hopena o ka synthesis, ua centrifuged ʻia ka hopena ma ka wikiwiki o 3000 min-1 no 5 mau minuke e wehe i nā derivatives polyethylene i hoʻoheheʻe ʻia. A laila, ua hoʻohui ʻia 2 mL o kahi hopena ICG 0.5 mg/mL i loko o dimethyl sulfoxide (DMSO) i ka hopena 2 mL. Hoʻopaʻa ʻia ka mea hoʻouluulu ma ka wikiwiki hoʻoulu o 300 min-1 no 2 mau hola. Hōʻike ʻia ke kiʻikuhi schematic o ka conjugate i loaʻa ma ke Kiʻi 2.
I loko o 200 mg MNP, ua hoʻohui mākou i 4 mL PLA-EDA-ICG conjugate. E hoʻohana i kahi mea lūlū LS-220 (LOIP, Rusia) e hoʻoulu i ka hoʻokuʻu ʻana no 30 mau minuke ma ke alapine o 300 min-1. A laila, ua holoi ʻia me ka isopropanol ʻekolu manawa a ua hoʻokaʻawale ʻia me ka magnetic. E hoʻohana i ka UZD-2 Ultrasonic Disperser (FSUE NII TVCH, Rusia) e hoʻohui i ka IPA i ka hoʻokuʻu ʻana no 5-10 mau minuke ma lalo o ka hana ultrasonic hoʻomau. Ma hope o ke kolu o ka holoi ʻana o ka IPA, ua holoi ʻia ka precipitate me ka wai distilled a ua hoʻokuʻu hou ʻia i loko o ka saline physiological ma kahi ʻano o 2 mg/mL.
Ua hoʻohana ʻia nā lako ZetaSizer Ultra (Malvern Instruments, UK) e aʻo i ka hoʻolaha nui o ka MNP i loaʻa i loko o ka hopena wai. Ua hoʻohana ʻia kahi microscope electron transmission (TEM) me kahi cathode hoʻokuʻu kahua JEM-1400 STEM (JEOL, Iapana) e aʻo i ke ʻano a me ka nui o ka MNP.
Ma kēia haʻawina, hoʻohana mākou i nā magnet paʻa cylindrical (papa N35; me ka uhi pale nickel) a me nā nui maʻamau e hiki mai ana (lōʻihi o ke axis × anawaena cylinder): 0.5 × 2 mm, 2 × 2 mm, 3 × 2 mm a me 5 × 2 mm.
Ua hoʻokō ʻia ke aʻo ʻana in vitro o ka lawe ʻana o MNP i loko o ka ʻōnaehana hoʻohālike ma luna o kahi scaffold hydrodynamic i hoʻomohala ʻia e ka Institute of Experimental Medicine o ke Almazov State Medical Research Center o ke Kuhina Ola o Rūsia. ʻO ka nui o ka wai e kahe ana (wai distilled a i ʻole ka hopena Krebs-Henseleit) he 225 mL. Hoʻohana ʻia nā magnet cylindrical axially magnetized ma ke ʻano he magnet mau. E kau i ka magnet ma luna o kahi mea paʻa 1.5 mm ka mamao mai ka paia o loko o ka paipu aniani waena, me kona hopena e kū pono ana i ke kuhikuhi o ka paipu (kū). ʻO ka nui o ke kahe ʻana o ka wai i loko o ka loop pani ʻia he 60 L/h (e like me ka wikiwiki linear o 0.225 m/s). Hoʻohana ʻia ka hopena Krebs-Henseleit ma ke ʻano he wai e kahe ana no ka mea he analog ia o ka plasma. ʻO ke coefficient viscosity dynamic o ka plasma he 1.1–1.3 mPa∙s. 9 Hoʻoholo ʻia ka nui o MNP i hoʻopili ʻia i loko o ke kahua magnetic e ka spectrophotometry mai ka nui o ka hao i loko o ka wai e kahe ana ma hope o ka hoʻokolohua.
Eia kekahi, ua hana ʻia nā haʻawina hoʻokolohua ma kahi papa hana mechanics fluid i hoʻomaikaʻi ʻia e hoʻoholo i ka permeability pili o nā kīʻaha koko. Hōʻike ʻia nā ʻāpana nui o ke kākoʻo hydrodynamic ma ke Kiʻi 3. ʻO nā ʻāpana nui o ka stent hydrodynamic he loop pani e hoʻohālike ana i ka ʻāpana keʻa o ka ʻōnaehana vascular hoʻohālike a me kahi pahu mālama. Hāʻawi ʻia ka neʻe ʻana o ka wai hoʻohālike ma ke ʻano o ka module kīʻaha koko e kahi pamu peristaltic. I ka wā o ka hoʻokolohua, e mālama i ka vaporization a me ka pae mahana e pono ai, a e nānā i nā ʻāpana ʻōnaehana (mahana, kaomi, ka nui o ke kahe wai, a me ka waiwai pH).
Kiʻi 3 Kiʻikuhi poloka o ka hoʻonohonoho i hoʻohana ʻia e aʻo i ka permeability o ka paia o ke aʻa carotid. 1-pahu mālama, 2-pamu peristaltic, 3-ʻano hana no ka hoʻokomo ʻana i ka hoʻokuʻu ʻana me ka MNP i loko o ka loop, 4-mika kahe, 5-mea ʻike kaomi i loko o ka loop, 6-mea hoʻololi wela, 7-lumi me ka ipu, 8-ke kumu o ke kahua magnetic, 9-ka balloon me nā hydrocarbons.
ʻO ke keʻena e loaʻa ana ka ipu, aia i ʻekolu mau ipu: kahi ipu nui ma waho a me ʻelua mau ipu liʻiliʻi, kahi e hele ai nā lima o ke kaapuni waena. Hoʻokomo ʻia ka cannula i loko o ka ipu liʻiliʻi, ua kaula ʻia ka ipu ma luna o ka ipu liʻiliʻi, a ua nakinaki paʻa ʻia ka piko o ka cannula me kahi uea lahilahi. Ua hoʻopiha ʻia ka hakahaka ma waena o ka ipu nui a me ka ipu liʻiliʻi me ka wai i hoʻoheheʻe ʻia, a noho mau ka mahana ma muli o ka pili ʻana i ka mea hoʻololi wela. Ua hoʻopiha ʻia ka hakahaka i loko o ka ipu liʻiliʻi me ka hopena Krebs-Henseleit e mālama i ke ola o nā ʻāpana kīʻaha koko. Ua hoʻopiha pū ʻia ka pahu me ka hopena Krebs-Henseleit. Hoʻohana ʻia ka ʻōnaehana hoʻolako kinoea (kalapona) e hoʻomāhu i ka hopena i loko o ka ipu liʻiliʻi i loko o ka pahu mālama a me ke keʻena e loaʻa ana ka ipu (Kiʻi 4).
Kiʻi 4 Ke keʻena kahi i waiho ʻia ai ka ipu. 1-Cannula no ka hoʻohaʻahaʻa ʻana i nā kīʻaha koko, 2-Keʻena waho, 3-Keʻena liʻiliʻi. Hōʻike ka pua i ke kuhikuhi o ke wai hoʻohālike.
No ka hoʻoholo ʻana i ka helu kuhikuhi permeability pili o ka paia o ke kīʻaha koko, ua hoʻohana ʻia ke aʻa carotid iole.
ʻO ka hoʻokomo ʻana o ka hoʻokuʻu ʻana o MNP (0.5mL) i loko o ka ʻōnaehana he mau ʻano penei: ʻo ka nui o loko o ka pahu a me ka paipu hoʻohui i loko o ka loop he 20mL, a ʻo ka nui o loko 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. Hoʻokomo ʻia ma luna o kekahi o nā keʻena liʻiliʻi, 1 cm ka mamao mai ka pahu, me kekahi ʻaoʻao e kū pono ana i ka paia o ka pahu. Mālama ʻia ka mahana ma 37 ° C. Hoʻonohonoho ʻia ka mana o ka pamu wili i 50%, kahi e kūlike ana me ka wikiwiki o 17 cm / s. Ma ke ʻano he kaohi, ua lawe ʻia nā laʻana i loko o kahi cell me ka ʻole o nā magnet mau loa.
Hoʻokahi hola ma hope o ka hoʻokomo ʻana o kahi ʻano MNP i hāʻawi ʻia, ua lawe ʻia kahi hāpana wai mai loko mai o ke keʻena. Ua ana ʻia ka ʻano o nā ʻāpana e kahi spectrophotometer me ka hoʻohana ʻana iā Unico 2802S UV-Vis spectrophotometer (United Products & Instruments, USA). Ma ka noʻonoʻo ʻana i ka spectrum absorption o ka hoʻokuʻu ʻana o ka MNP, ua hana ʻia ke ana ʻana ma 450 nm.
Wahi a nā alakaʻi Rus-LASA-FELASA, ua hānai ʻia nā holoholona a pau i loko o nā hale kūikawā i ʻole nā ​​pathogen. Ua kūlike kēia haʻawina me nā lula pono āpau no nā hoʻokolohua holoholona a me ka noiʻi, a ua loaʻa iā ia ka ʻae pono mai ke Almazov National Medical Research Center (IACUC). Ua inu nā holoholona i ka wai ad libitum a ua hānai mau ʻia.
Ua mālama ʻia ke aʻo ʻana ma luna o 10 mau ʻiole NSG kāne 12-pule i hoʻomaʻamaʻa ʻia me ka immunodeficiency (NOD.Cg-Prkdcscid Il2rgtm1Wjl/Szj, Jackson Laboratory, USA) 10, me ke kaumaha he 22 g ± 10%. Ma muli o ka hoʻopau ʻia ʻana o ka pale ʻana o nā ʻiole immunodeficiency, ʻae nā ʻiole immunodeficiency o kēia laina i ka hoʻoili ʻana o nā pūnaewele kanaka a me nā ʻiʻo me ka hōʻole ʻole ʻana i ka hoʻoili ʻana. Ua hoʻokaʻawale ʻia nā hoa litter mai nā hale paʻa like ʻole i ka hui hoʻokolohua, a ua hoʻohua pū ʻia lākou a i ʻole ua hōʻike ʻia 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 kanaka HeLa e hoʻokumu i kahi kumu hoʻohālike xenograft. Ua ulu ʻia nā cell i loko o DMEM me ka glutamine (PanEco, Rusia), i hoʻohui ʻia me 10% fetal bovine serum (Hyclone, USA), 100 CFU/mL penicillin, a me 100 μg/mL streptomycin. Ua hāʻawi lokomaikaʻi ʻia ka laina cell e ka Gene Expression Regulation Laboratory o ka Institute of Cell Research of the Russian Academy of Sciences. Ma mua o ka hoʻokomo ʻana, ua wehe ʻia nā cell HeLa mai ka plastic culture me kahi 1:1 trypsin:Versene solution (Biolot, Rusia). Ma hope o ka holoi ʻana, ua hoʻokuʻu ʻia nā cell i loko o ka medium piha i kahi ʻano o 5 × 106 mau cell no 200 μL, a ua hoʻokahe ʻia me ka matrix membrane basement (LDEV-FREE, MATRIGEL® CORNING®) (1:1, ma luna o ka hau). Ua hoʻokomo ʻia ka hoʻokuʻu cell i hoʻomākaukau ʻia ma ke ʻano subcutaneous i loko o ka ʻili o ka ʻūhā ʻiole. E hoʻohana i nā calipers uila e nānā i ka ulu ʻana o ka tumor i kēlā me kēia 3 lā.
I ka hiki ʻana o ka puʻupuʻu i 500 mm3, ua hoʻokomo ʻia kahi magnet mau loa i loko o nā ʻiʻo o ka holoholona hoʻokolohua kokoke i ka puʻupuʻu. I loko o ka hui hoʻokolohua (MNPs-ICG + tumor-M), ua hoʻokomo ʻia he 0.1 mL o ka hoʻokuʻu MNP a ua hōʻike ʻia i kahi kahua magnetic. Ua hoʻohana ʻia nā holoholona holoʻokoʻa i mālama ʻole ʻia ma ke ʻano he mau kaohi (hope). Eia kekahi, ua hoʻohana ʻia nā holoholona i hoʻokomo ʻia me 0.1 mL o MNP akā ʻaʻole i hoʻokomo ʻia me nā magnets (MNPs-ICG + tumor-BM).
Ua hana ʻia ka nānā ʻana i ka fluorescence o nā laʻana in vivo a me in vitro ma ka IVIS Lumina LT series III bioimager (PerkinElmer Inc., USA). No ka nānā ʻana i ka in vitro, ua hoʻohui ʻia kahi nui o 1 mL o ka synthetic PLA-EDA-ICG a me MNP-PLA-EDA-ICG conjugate i nā lua pā. Ma ka noʻonoʻo ʻana i nā ʻano fluorescence o ka dye ICG, ua koho ʻia ke kānana maikaʻi loa i hoʻohana ʻia e hoʻoholo i ka ikaika luminous o ka laʻana: ʻo ka lōʻihi o ka hoʻonāukiuki he 745 nm, a ʻo ka lōʻihi o ka hoʻokuʻu ʻana he 815 nm. Ua hoʻohana ʻia ka polokalamu Living Image 4.5.5 (PerkinElmer Inc.) e ana i ka ikaika fluorescence o nā lua i loaʻa ka conjugate.
Ua ana ʻia ka ikaika fluorescence a me ka hōʻiliʻili ʻana o ka MNP-PLA-EDA-ICG conjugate i loko o nā ʻiole hoʻohālike tumor in vivo, me ka ʻole o ke alo a me ka hoʻopili ʻana o kahi kahua magnetic ma kahi hoihoi. Ua hoʻomaʻamaʻa ʻia nā ʻiole me ka isoflurane, a laila ua hoʻokomo ʻia he 0.1 mL o ka MNP-PLA-EDA-ICG conjugate ma o ke aʻa huelo. Ua hoʻohana ʻia nā ʻiole i mālama ʻole ʻia ma ke ʻano he kaohi maikaʻi ʻole e loaʻa ai kahi ʻano fluorescent. Ma hope o ka hāʻawi ʻana i ka conjugate ma ke ʻano intravenous, e kau i ka holoholona ma kahi kahua hoʻomehana (37°C) i loko o ke keʻena o ka IVIS Lumina LT series III fluorescence imager (PerkinElmer Inc.) me ka mālama ʻana i ka hanu ʻana me 2% isoflurane anesthetization. E hoʻohana i ke kānana i kūkulu ʻia e 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 ʻana i ka hōʻiliʻili ʻana o ka conjugate i loko o ka puʻupuʻu, 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 me 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 pepehi kanaka ʻia nā holoholona e kahi overdose o ka isoflurane anesthesia no ka hoʻokaʻawale ʻana o nā wahi puʻupuʻu a me ka loiloi quantitative o ka fluorescence radiation. E hoʻohana i ka polokalamu Living Image 4.5.5 (PerkinElmer Inc.) e hana lima i ka nānā ʻana i ka hōʻailona mai ka ʻāpana hoihoi i koho ʻia. Ua lawe ʻia ʻekolu mau ana no kēlā me kēia holoholona (n = 9).
Ma kēia haʻawina, ʻaʻole mākou i helu i ka hoʻouka pono ʻana o ICG ma luna o MNPs-ICG. Eia kekahi, ʻaʻole mākou i hoʻohālikelike i ka pono o ka paʻa ʻana o nā nanoparticles ma lalo o ka mana o nā magnet mau o nā ʻano like ʻole. Eia kekahi, ʻaʻole mākou i loiloi i ka hopena lōʻihi o ke kahua magnetic ma ka paʻa ʻana o nā nanoparticles i loko o nā ʻiʻo tumor.
ʻOi aku ka nui o nā nanoparticles, me ka awelika o 195.4 nm. Eia kekahi, aia nā agglomerates i loko o ka hoʻokuʻu ʻana me ka awelika o 1176.0 nm (Kiʻi 5A). Ma hope mai, ua kānana ʻia ka ʻāpana ma o kahi kānana centrifugal. ʻO ka zeta potential o nā ʻāpana he -15.69 mV (Kiʻi 5B).
Kiʻi 5 Nā ʻano kino o ka hoʻokuʻu ʻana: (A) ka hoʻolaha ʻana o ka nui o nā ʻāpana; (B) ka hoʻolaha ʻana o nā ʻāpana ma ka hiki ke zeta; (C) kiʻi TEM o nā nanoparticles.
ʻO ka nui o ka ʻāpana he 200 nm (Kiʻi 5C), i haku ʻia me kahi MNP hoʻokahi me ka nui o 20 nm, a me kahi pūpū organik i hoʻohui ʻia ʻo PLA-EDA-ICG me kahi haʻahaʻa o ka nui o ka electron. Hiki ke wehewehe ʻia ke kūkulu ʻia ʻana o nā agglomerates i loko o nā hopena wai e ka modulus haʻahaʻa o ka ikaika electromotive o nā nanoparticles pākahi.
No nā magnet paʻa, ke kau ʻia ka magnetization ma ka leo V, ua māhele ʻia ka hōʻike integral i ʻelua integrals, ʻo ia hoʻi ka leo a me ka ʻili:
I ke ʻano o kahi hāpana me ka magnetization mau, ʻo ka nui o ke au he ʻole. A laila, e like ke ʻano o ka hōʻike ʻana o ka vector induction magnetic:
E hoʻohana i ka polokalamu MATLAB (MathWorks, Inc., USA) no ka helu helu ʻana, ʻo ETU "LETI" helu laikini hoʻonaʻauao 40502181.
E like me ka mea i hōʻike ʻia ma ke Kiʻi 7 Kiʻi 8 Kiʻi 9 Kiʻi-10, ua hoʻoulu ʻia ke kahua magnetic ikaika loa e kahi magnet i kuhikuhi ʻia ma ke axial mai ka hopena o ka cylinder. ʻO ka radius hana kūpono e like me ke geometry o ka magnet. I loko o nā magnet cylindrical me kahi cylinder nona ka lōʻihi i ʻoi aku ma mua o kona anawaena, ʻike ʻia ke kahua magnetic ikaika loa ma ke kuhikuhi axial-radial (no ka ʻāpana pili); no laila, ʻo kahi pālua o nā cylinders me kahi lakio hiʻohiʻona nui aʻe (diameter a me ka lōʻihi) MNP adsorption ka mea kūpono loa.
Kiʻi 7 ʻO ka ʻāpana o ka ikaika hoʻokomo 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 hoʻokomo magnetic Br he kū pololei i ka axis magnet Oz; ʻo 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 ʻāpana ikaika hoʻokomo magnetic Bz ma ka mamao r mai ke axis 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 ʻĀpana hoʻokomo magnetic ma ke kuhikuhi radial; ka nui o ka magnet maʻamau: laina ʻeleʻele 0.5 × 2mm, laina polū 2 × 2mm, laina ʻōmaʻomaʻo 3 × 2mm, laina ʻulaʻula 5 × 2mm.
Hiki ke hoʻohana ʻia nā kumu hoʻohālike hydrodynamic kūikawā e aʻo ai i ke ʻano o ka lawe ʻana o MNP i nā ʻiʻo tumor, e hoʻopaʻa i nā nanoparticles ma kahi i manaʻo ʻia, a hoʻoholo i ke ʻano o nā nanoparticles ma lalo o nā kūlana hydrodynamic i loko o ka ʻōnaehana circulatory. Hiki ke hoʻohana ʻia nā magnet mau loa ma ke ʻano he mau kahua magnetic waho. Inā mākou e hoʻowahāwahā i ka pilina magnetostatic ma waena o nā nanoparticles a ʻaʻole e noʻonoʻo i ke kumu hoʻohālike wai magnetic, ua lawa ia e kuhi i ka pilina ma waena o ka magnet a me kahi nanoparticle hoʻokahi me kahi dipole-dipole approximation.
ʻO m ka manawa magnetic o ka magnet, ʻo r ka vector radius o ke kiko kahi i loaʻa ai ka nanoparticle, a ʻo k ka factor ʻōnaehana. I ka dipole approximation, ua like ke ʻano o ke kahua o ka magnet (Kiʻi 11).
I loko o kahi kahua magnetic like, hoʻohuli wale nā ​​​​nanoparticles ma nā laina o ka ikaika. I loko o kahi kahua magnetic like ʻole, hana ka ikaika ma luna ona:
ʻAuhea ka derivative o kahi kuhikuhi i hāʻawi ʻia l. Eia kekahi, huki ka ikaika i nā nanoparticles i loko o nā wahi ʻokoʻa loa o ke kahua, ʻo ia hoʻi, piʻi ka curvature a me ka density o nā laina o ka ikaika.
No laila, he mea makemake ʻia e hoʻohana i kahi magnet ikaika (a i ʻole ke kaulahao magnet) me ka anisotropy axial maopopo ma kahi i loaʻa ai nā ʻāpana.
Hōʻike ka Papa 1 i ka hiki o kahi magnet hoʻokahi ma ke ʻano he kumu kahua magnetic lawa e hopu a mālama i ka MNP i loko o ka moena vascular o ke kahua noi.