JP2017529156A - 磁気共鳴画像法用途のためのナノ粒子 - Google Patents
磁気共鳴画像法用途のためのナノ粒子 Download PDFInfo
- Publication number
- JP2017529156A JP2017529156A JP2017514658A JP2017514658A JP2017529156A JP 2017529156 A JP2017529156 A JP 2017529156A JP 2017514658 A JP2017514658 A JP 2017514658A JP 2017514658 A JP2017514658 A JP 2017514658A JP 2017529156 A JP2017529156 A JP 2017529156A
- Authority
- JP
- Japan
- Prior art keywords
- nanoparticles
- ligand
- zwitterionic
- contrast agent
- nanoparticle
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- 239000002105 nanoparticle Substances 0.000 title claims abstract description 122
- 238000002595 magnetic resonance imaging Methods 0.000 title claims abstract description 27
- 239000003446 ligand Substances 0.000 claims abstract description 54
- 150000001875 compounds Chemical class 0.000 claims abstract description 23
- 238000004519 manufacturing process Methods 0.000 claims abstract description 7
- 239000011248 coating agent Substances 0.000 claims abstract description 6
- 238000000576 coating method Methods 0.000 claims abstract description 6
- 230000001590 oxidative effect Effects 0.000 claims abstract description 4
- UQSXHKLRYXJYBZ-UHFFFAOYSA-N Iron oxide Chemical compound [Fe]=O UQSXHKLRYXJYBZ-UHFFFAOYSA-N 0.000 claims description 38
- VYFYYTLLBUKUHU-UHFFFAOYSA-N dopamine Chemical compound NCCC1=CC=C(O)C(O)=C1 VYFYYTLLBUKUHU-UHFFFAOYSA-N 0.000 claims description 36
- 239000002872 contrast media Substances 0.000 claims description 29
- 238000000034 method Methods 0.000 claims description 29
- 239000002904 solvent Substances 0.000 claims description 22
- 229960003638 dopamine Drugs 0.000 claims description 18
- BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 claims description 15
- 239000000203 mixture Substances 0.000 claims description 11
- 239000002253 acid Substances 0.000 claims description 9
- 239000003153 chemical reaction reagent Substances 0.000 claims description 9
- GQEZCXVZFLOKMC-UHFFFAOYSA-N 1-hexadecene Chemical compound CCCCCCCCCCCCCCC=C GQEZCXVZFLOKMC-UHFFFAOYSA-N 0.000 claims description 8
- CCCMONHAUSKTEQ-UHFFFAOYSA-N octadec-1-ene Chemical compound CCCCCCCCCCCCCCCCC=C CCCMONHAUSKTEQ-UHFFFAOYSA-N 0.000 claims description 8
- SPURMHFLEKVAAS-UHFFFAOYSA-N 1-docosene Chemical compound CCCCCCCCCCCCCCCCCCCCC=C SPURMHFLEKVAAS-UHFFFAOYSA-N 0.000 claims description 6
- 238000002583 angiography Methods 0.000 claims description 6
- VAMFXQBUQXONLZ-UHFFFAOYSA-N n-alpha-eicosene Natural products CCCCCCCCCCCCCCCCCCC=C VAMFXQBUQXONLZ-UHFFFAOYSA-N 0.000 claims description 6
- 239000002122 magnetic nanoparticle Substances 0.000 claims description 5
- WRIDQFICGBMAFQ-UHFFFAOYSA-N (E)-8-Octadecenoic acid Natural products CCCCCCCCCC=CCCCCCCC(O)=O WRIDQFICGBMAFQ-UHFFFAOYSA-N 0.000 claims description 4
- LQJBNNIYVWPHFW-UHFFFAOYSA-N 20:1omega9c fatty acid Natural products CCCCCCCCCCC=CCCCCCCCC(O)=O LQJBNNIYVWPHFW-UHFFFAOYSA-N 0.000 claims description 4
- QSBYPNXLFMSGKH-UHFFFAOYSA-N 9-Heptadecensaeure Natural products CCCCCCCC=CCCCCCCCC(O)=O QSBYPNXLFMSGKH-UHFFFAOYSA-N 0.000 claims description 4
- 239000005642 Oleic acid Substances 0.000 claims description 4
- ZQPPMHVWECSIRJ-UHFFFAOYSA-N Oleic acid Natural products CCCCCCCCC=CCCCCCCCC(O)=O ZQPPMHVWECSIRJ-UHFFFAOYSA-N 0.000 claims description 4
- HOIQWTMREPWSJY-GNOQXXQHSA-K iron(3+);(z)-octadec-9-enoate Chemical compound [Fe+3].CCCCCCCC\C=C/CCCCCCCC([O-])=O.CCCCCCCC\C=C/CCCCCCCC([O-])=O.CCCCCCCC\C=C/CCCCCCCC([O-])=O HOIQWTMREPWSJY-GNOQXXQHSA-K 0.000 claims description 4
- QXJSBBXBKPUZAA-UHFFFAOYSA-N isooleic acid Natural products CCCCCCCC=CCCCCCCCCC(O)=O QXJSBBXBKPUZAA-UHFFFAOYSA-N 0.000 claims description 4
- ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 claims description 4
- 229940106006 1-eicosene Drugs 0.000 claims description 3
- FIKTURVKRGQNQD-UHFFFAOYSA-N 1-eicosene Natural products CCCCCCCCCCCCCCCCCC=CC(O)=O FIKTURVKRGQNQD-UHFFFAOYSA-N 0.000 claims description 3
- 235000021355 Stearic acid Nutrition 0.000 claims description 3
- 150000003973 alkyl amines Chemical class 0.000 claims description 3
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 claims description 3
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 claims description 3
- 239000008117 stearic acid Substances 0.000 claims description 3
- 230000005389 magnetism Effects 0.000 claims description 2
- 239000008186 active pharmaceutical agent Substances 0.000 claims 2
- 230000012010 growth Effects 0.000 description 14
- 229940031182 nanoparticles iron oxide Drugs 0.000 description 14
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 12
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 11
- -1 cyano, nitro, amino, carboxy Chemical group 0.000 description 10
- 241000699670 Mus sp. Species 0.000 description 9
- 238000009826 distribution Methods 0.000 description 9
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 8
- 239000002245 particle Substances 0.000 description 8
- 241000699666 Mus <mouse, genus> Species 0.000 description 7
- 210000004369 blood Anatomy 0.000 description 7
- 239000008280 blood Substances 0.000 description 7
- LGMLJQFQKXPRGA-VPVMAENOSA-K gadopentetate dimeglumine Chemical compound [Gd+3].CNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO.CNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO.OC(=O)CN(CC([O-])=O)CCN(CC([O-])=O)CCN(CC(O)=O)CC([O-])=O LGMLJQFQKXPRGA-VPVMAENOSA-K 0.000 description 7
- 238000001727 in vivo Methods 0.000 description 7
- 239000011541 reaction mixture Substances 0.000 description 7
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 6
- 238000003384 imaging method Methods 0.000 description 6
- 239000000463 material Substances 0.000 description 6
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 6
- 229910052760 oxygen Inorganic materials 0.000 description 6
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 6
- 208000003174 Brain Neoplasms Diseases 0.000 description 5
- 229910052688 Gadolinium Inorganic materials 0.000 description 5
- 241001465754 Metazoa Species 0.000 description 5
- XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Natural products P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 description 5
- 125000003118 aryl group Chemical group 0.000 description 5
- 210000004556 brain Anatomy 0.000 description 5
- UIWYJDYFSGRHKR-UHFFFAOYSA-N gadolinium atom Chemical compound [Gd] UIWYJDYFSGRHKR-UHFFFAOYSA-N 0.000 description 5
- 229910052742 iron Inorganic materials 0.000 description 5
- 230000008569 process Effects 0.000 description 5
- 208000032612 Glial tumor Diseases 0.000 description 4
- 206010018338 Glioma Diseases 0.000 description 4
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 4
- 241000700159 Rattus Species 0.000 description 4
- 239000007983 Tris buffer Substances 0.000 description 4
- 125000000217 alkyl group Chemical group 0.000 description 4
- 125000003277 amino group Chemical group 0.000 description 4
- 229940039231 contrast media Drugs 0.000 description 4
- 125000001072 heteroaryl group Chemical group 0.000 description 4
- WTFXARWRTYJXII-UHFFFAOYSA-N iron(2+);iron(3+);oxygen(2-) Chemical compound [O-2].[O-2].[O-2].[O-2].[Fe+2].[Fe+3].[Fe+3] WTFXARWRTYJXII-UHFFFAOYSA-N 0.000 description 4
- 230000006911 nucleation Effects 0.000 description 4
- 238000010899 nucleation Methods 0.000 description 4
- 229910052698 phosphorus Inorganic materials 0.000 description 4
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 4
- 125000001273 sulfonato group Chemical class [O-]S(*)(=O)=O 0.000 description 4
- 230000008685 targeting Effects 0.000 description 4
- 108010017384 Blood Proteins Proteins 0.000 description 3
- 102000004506 Blood Proteins Human genes 0.000 description 3
- 238000000862 absorption spectrum Methods 0.000 description 3
- 125000003545 alkoxy group Chemical group 0.000 description 3
- 150000001412 amines Chemical class 0.000 description 3
- 210000004204 blood vessel Anatomy 0.000 description 3
- 238000009835 boiling Methods 0.000 description 3
- 239000013078 crystal Substances 0.000 description 3
- 150000002430 hydrocarbons Chemical group 0.000 description 3
- 230000002209 hydrophobic effect Effects 0.000 description 3
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 3
- 230000003993 interaction Effects 0.000 description 3
- 229910052757 nitrogen Inorganic materials 0.000 description 3
- 229910000073 phosphorus hydride Inorganic materials 0.000 description 3
- 102000004169 proteins and genes Human genes 0.000 description 3
- 108090000623 proteins and genes Proteins 0.000 description 3
- 238000011160 research Methods 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- XSOKHXFFCGXDJZ-UHFFFAOYSA-N telluride(2-) Chemical compound [Te-2] XSOKHXFFCGXDJZ-UHFFFAOYSA-N 0.000 description 3
- 150000003573 thiols Chemical class 0.000 description 3
- 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 3
- RMZAYIKUYWXQPB-UHFFFAOYSA-N trioctylphosphane Chemical compound CCCCCCCCP(CCCCCCCC)CCCCCCCC RMZAYIKUYWXQPB-UHFFFAOYSA-N 0.000 description 3
- ZMBHCYHQLYEYDV-UHFFFAOYSA-N trioctylphosphine oxide Chemical compound CCCCCCCCP(=O)(CCCCCCCC)CCCCCCCC ZMBHCYHQLYEYDV-UHFFFAOYSA-N 0.000 description 3
- 210000002700 urine Anatomy 0.000 description 3
- 150000005206 1,2-dihydroxybenzenes Chemical class 0.000 description 2
- HFDVRLIODXPAHB-UHFFFAOYSA-N 1-tetradecene Chemical compound CCCCCCCCCCCCC=C HFDVRLIODXPAHB-UHFFFAOYSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- GYHNNYVSQQEPJS-UHFFFAOYSA-N Gallium Chemical group [Ga] GYHNNYVSQQEPJS-UHFFFAOYSA-N 0.000 description 2
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical group [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 2
- 206010028980 Neoplasm Diseases 0.000 description 2
- 229910019142 PO4 Inorganic materials 0.000 description 2
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 2
- 239000002202 Polyethylene glycol Substances 0.000 description 2
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical group [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 2
- 230000002776 aggregation Effects 0.000 description 2
- 238000004220 aggregation Methods 0.000 description 2
- 125000003342 alkenyl group Chemical group 0.000 description 2
- 125000000304 alkynyl group Chemical group 0.000 description 2
- 229910052782 aluminium Inorganic materials 0.000 description 2
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical group [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 2
- 150000003863 ammonium salts Chemical class 0.000 description 2
- WATWJIUSRGPENY-UHFFFAOYSA-N antimony atom Chemical compound [Sb] WATWJIUSRGPENY-UHFFFAOYSA-N 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 229910052785 arsenic Inorganic materials 0.000 description 2
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 230000027455 binding Effects 0.000 description 2
- 229910052793 cadmium Inorganic materials 0.000 description 2
- BDOSMKKIYDKNTQ-UHFFFAOYSA-N cadmium atom Chemical group [Cd] BDOSMKKIYDKNTQ-UHFFFAOYSA-N 0.000 description 2
- YCIMNLLNPGFGHC-UHFFFAOYSA-N catechol Chemical compound OC1=CC=CC=C1O YCIMNLLNPGFGHC-UHFFFAOYSA-N 0.000 description 2
- 150000004770 chalcogenides Chemical class 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 230000007423 decrease Effects 0.000 description 2
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 229940086604 feraheme Drugs 0.000 description 2
- 229910052733 gallium Inorganic materials 0.000 description 2
- 125000005843 halogen group Chemical group 0.000 description 2
- 125000000592 heterocycloalkyl group Chemical group 0.000 description 2
- 238000004128 high performance liquid chromatography Methods 0.000 description 2
- 229910052739 hydrogen Inorganic materials 0.000 description 2
- 230000006872 improvement Effects 0.000 description 2
- 229910052738 indium Inorganic materials 0.000 description 2
- APFVFJFRJDLVQX-UHFFFAOYSA-N indium atom Chemical group [In] APFVFJFRJDLVQX-UHFFFAOYSA-N 0.000 description 2
- 238000001990 intravenous administration Methods 0.000 description 2
- 210000003734 kidney Anatomy 0.000 description 2
- 229910052749 magnesium Inorganic materials 0.000 description 2
- 239000011777 magnesium Chemical group 0.000 description 2
- QSHDDOUJBYECFT-UHFFFAOYSA-N mercury Chemical group [Hg] QSHDDOUJBYECFT-UHFFFAOYSA-N 0.000 description 2
- 229910052753 mercury Inorganic materials 0.000 description 2
- 229910052751 metal Inorganic materials 0.000 description 2
- 239000002184 metal Substances 0.000 description 2
- 238000012544 monitoring process Methods 0.000 description 2
- 238000010172 mouse model Methods 0.000 description 2
- 230000007935 neutral effect Effects 0.000 description 2
- 125000001181 organosilyl group Chemical group [SiH3]* 0.000 description 2
- 239000001301 oxygen Substances 0.000 description 2
- 210000001539 phagocyte Anatomy 0.000 description 2
- 235000021317 phosphate Nutrition 0.000 description 2
- 239000002953 phosphate buffered saline Substances 0.000 description 2
- 239000011574 phosphorus Substances 0.000 description 2
- 229920001223 polyethylene glycol Polymers 0.000 description 2
- 238000001556 precipitation Methods 0.000 description 2
- 239000011669 selenium Substances 0.000 description 2
- 150000003346 selenoethers Chemical class 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 229910052717 sulfur Inorganic materials 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 229910052716 thallium Chemical group 0.000 description 2
- BKVIYDNLLOSFOA-UHFFFAOYSA-N thallium Chemical group [Tl] BKVIYDNLLOSFOA-UHFFFAOYSA-N 0.000 description 2
- UYPYRKYUKCHHIB-UHFFFAOYSA-N trimethylamine N-oxide Chemical compound C[N+](C)(C)[O-] UYPYRKYUKCHHIB-UHFFFAOYSA-N 0.000 description 2
- 229910052725 zinc Inorganic materials 0.000 description 2
- 239000011701 zinc Chemical group 0.000 description 2
- YBNMDCCMCLUHBL-UHFFFAOYSA-N (2,5-dioxopyrrolidin-1-yl) 4-pyren-1-ylbutanoate Chemical compound C=1C=C(C2=C34)C=CC3=CC=CC4=CC=C2C=1CCCC(=O)ON1C(=O)CCC1=O YBNMDCCMCLUHBL-UHFFFAOYSA-N 0.000 description 1
- 125000006555 (C3-C5) cycloalkyl group Chemical group 0.000 description 1
- FSSPGSAQUIYDCN-UHFFFAOYSA-N 1,3-Propane sultone Chemical compound O=S1(=O)CCCO1 FSSPGSAQUIYDCN-UHFFFAOYSA-N 0.000 description 1
- YHBWXWLDOKIVCJ-UHFFFAOYSA-N 2-[2-(2-methoxyethoxy)ethoxy]acetic acid Chemical compound COCCOCCOCC(O)=O YHBWXWLDOKIVCJ-UHFFFAOYSA-N 0.000 description 1
- YICAEXQYKBMDNH-UHFFFAOYSA-N 3-[bis(3-hydroxypropyl)phosphanyl]propan-1-ol Chemical compound OCCCP(CCCO)CCCO YICAEXQYKBMDNH-UHFFFAOYSA-N 0.000 description 1
- AUDYZXNUHIIGRB-UHFFFAOYSA-N 3-thiophen-2-ylpyrrole-2,5-dione Chemical compound O=C1NC(=O)C(C=2SC=CC=2)=C1 AUDYZXNUHIIGRB-UHFFFAOYSA-N 0.000 description 1
- 229910017115 AlSb Inorganic materials 0.000 description 1
- 108091023037 Aptamer Proteins 0.000 description 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- 102000014914 Carrier Proteins Human genes 0.000 description 1
- 229910004613 CdTe Inorganic materials 0.000 description 1
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
- MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 description 1
- 239000012692 Fe precursor Substances 0.000 description 1
- 206010016654 Fibrosis Diseases 0.000 description 1
- 229910002601 GaN Inorganic materials 0.000 description 1
- 229910005540 GaP Inorganic materials 0.000 description 1
- 229910005542 GaSb Inorganic materials 0.000 description 1
- 229910001218 Gallium arsenide Inorganic materials 0.000 description 1
- 229910004262 HgTe Inorganic materials 0.000 description 1
- 101001077673 Homo sapiens Voltage-gated hydrogen channel 1 Proteins 0.000 description 1
- 229910000673 Indium arsenide Inorganic materials 0.000 description 1
- GPXJNWSHGFTCBW-UHFFFAOYSA-N Indium phosphide Chemical compound [In]#P GPXJNWSHGFTCBW-UHFFFAOYSA-N 0.000 description 1
- 238000012307 MRI technique Methods 0.000 description 1
- PWHULOQIROXLJO-UHFFFAOYSA-N Manganese Chemical compound [Mn] PWHULOQIROXLJO-UHFFFAOYSA-N 0.000 description 1
- 229910017680 MgTe Inorganic materials 0.000 description 1
- 229910002665 PbTe Inorganic materials 0.000 description 1
- ABLZXFCXXLZCGV-UHFFFAOYSA-N Phosphorous acid Chemical class OP(O)=O ABLZXFCXXLZCGV-UHFFFAOYSA-N 0.000 description 1
- BUGBHKTXTAQXES-UHFFFAOYSA-N Selenium Chemical group [Se] BUGBHKTXTAQXES-UHFFFAOYSA-N 0.000 description 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
- UCKMPCXJQFINFW-UHFFFAOYSA-N Sulphide Chemical compound [S-2] UCKMPCXJQFINFW-UHFFFAOYSA-N 0.000 description 1
- OKJPEAGHQZHRQV-UHFFFAOYSA-N Triiodomethane Natural products IC(I)I OKJPEAGHQZHRQV-UHFFFAOYSA-N 0.000 description 1
- 102100025443 Voltage-gated hydrogen channel 1 Human genes 0.000 description 1
- 229910007709 ZnTe Inorganic materials 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 125000001931 aliphatic group Chemical group 0.000 description 1
- 125000004450 alkenylene group Chemical group 0.000 description 1
- 125000004453 alkoxycarbonyl group Chemical group 0.000 description 1
- 125000004448 alkyl carbonyl group Chemical group 0.000 description 1
- 125000005196 alkyl carbonyloxy group Chemical group 0.000 description 1
- 125000002947 alkylene group Chemical group 0.000 description 1
- 125000004419 alkynylene group Chemical group 0.000 description 1
- 230000003698 anagen phase Effects 0.000 description 1
- 238000000137 annealing Methods 0.000 description 1
- 229910052787 antimony Inorganic materials 0.000 description 1
- 239000012736 aqueous medium Substances 0.000 description 1
- RQNWIZPPADIBDY-UHFFFAOYSA-N arsenic atom Chemical compound [As] RQNWIZPPADIBDY-UHFFFAOYSA-N 0.000 description 1
- 125000000732 arylene group Chemical group 0.000 description 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
- 108091008324 binding proteins Proteins 0.000 description 1
- 239000013060 biological fluid Substances 0.000 description 1
- 230000005540 biological transmission Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- RLECCBFNWDXKPK-UHFFFAOYSA-N bis(trimethylsilyl)sulfide Chemical compound C[Si](C)(C)S[Si](C)(C)C RLECCBFNWDXKPK-UHFFFAOYSA-N 0.000 description 1
- 230000000740 bleeding effect Effects 0.000 description 1
- 230000008499 blood brain barrier function Effects 0.000 description 1
- 210000001218 blood-brain barrier Anatomy 0.000 description 1
- 229940098773 bovine serum albumin Drugs 0.000 description 1
- UHYPYGJEEGLRJD-UHFFFAOYSA-N cadmium(2+);selenium(2-) Chemical compound [Se-2].[Cd+2] UHYPYGJEEGLRJD-UHFFFAOYSA-N 0.000 description 1
- 125000004181 carboxyalkyl group Chemical group 0.000 description 1
- 150000007942 carboxylates Chemical class 0.000 description 1
- 230000000747 cardiac effect Effects 0.000 description 1
- 238000006555 catalytic reaction Methods 0.000 description 1
- 210000004027 cell Anatomy 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 230000001010 compromised effect Effects 0.000 description 1
- 230000021615 conjugation Effects 0.000 description 1
- 125000004093 cyano group Chemical group *C#N 0.000 description 1
- 125000005724 cycloalkenylene group Chemical group 0.000 description 1
- 125000000753 cycloalkyl group Chemical group 0.000 description 1
- 125000002993 cycloalkylene group Chemical group 0.000 description 1
- 230000007123 defense Effects 0.000 description 1
- 238000001212 derivatisation Methods 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 230000018109 developmental process Effects 0.000 description 1
- 238000003745 diagnosis Methods 0.000 description 1
- 238000002059 diagnostic imaging Methods 0.000 description 1
- 229910001882 dioxygen Inorganic materials 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- 239000002612 dispersion medium Substances 0.000 description 1
- 230000009881 electrostatic interaction Effects 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 230000007717 exclusion Effects 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000011554 ferrofluid Substances 0.000 description 1
- 230000004761 fibrosis Effects 0.000 description 1
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 1
- 150000002240 furans Chemical class 0.000 description 1
- 125000002541 furyl group Chemical group 0.000 description 1
- 229940075613 gadolinium oxide Drugs 0.000 description 1
- 229910001938 gadolinium oxide Inorganic materials 0.000 description 1
- CMIHHWBVHJVIGI-UHFFFAOYSA-N gadolinium(iii) oxide Chemical compound [O-2].[O-2].[O-2].[Gd+3].[Gd+3] CMIHHWBVHJVIGI-UHFFFAOYSA-N 0.000 description 1
- 125000001188 haloalkyl group Chemical group 0.000 description 1
- 125000005059 halophenyl group Chemical group 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 125000005549 heteroarylene group Chemical group 0.000 description 1
- 125000005842 heteroatom Chemical group 0.000 description 1
- 125000006588 heterocycloalkylene group Chemical group 0.000 description 1
- 231100000086 high toxicity Toxicity 0.000 description 1
- 238000002173 high-resolution transmission electron microscopy Methods 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
- UCNNJGDEJXIUCC-UHFFFAOYSA-L hydroxy(oxo)iron;iron Chemical compound [Fe].O[Fe]=O.O[Fe]=O UCNNJGDEJXIUCC-UHFFFAOYSA-L 0.000 description 1
- 125000002768 hydroxyalkyl group Chemical group 0.000 description 1
- 238000002513 implantation Methods 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- WPYVAWXEWQSOGY-UHFFFAOYSA-N indium antimonide Chemical compound [Sb]#[In] WPYVAWXEWQSOGY-UHFFFAOYSA-N 0.000 description 1
- RPQDHPTXJYYUPQ-UHFFFAOYSA-N indium arsenide Chemical compound [In]#[As] RPQDHPTXJYYUPQ-UHFFFAOYSA-N 0.000 description 1
- 150000002484 inorganic compounds Chemical class 0.000 description 1
- 229910010272 inorganic material Inorganic materials 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- SZVJSHCCFOBDDC-UHFFFAOYSA-N iron(II,III) oxide Inorganic materials O=[Fe]O[Fe]O[Fe]=O SZVJSHCCFOBDDC-UHFFFAOYSA-N 0.000 description 1
- JEIPFZHSYJVQDO-UHFFFAOYSA-N iron(III) oxide Inorganic materials O=[Fe]O[Fe]=O JEIPFZHSYJVQDO-UHFFFAOYSA-N 0.000 description 1
- 230000003907 kidney function Effects 0.000 description 1
- 230000002045 lasting effect Effects 0.000 description 1
- 230000031700 light absorption Effects 0.000 description 1
- 125000005647 linker group Chemical group 0.000 description 1
- 231100001252 long-term toxicity Toxicity 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 230000005415 magnetization Effects 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 229910052748 manganese Inorganic materials 0.000 description 1
- 239000011572 manganese Substances 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 229910021645 metal ion Inorganic materials 0.000 description 1
- 238000001465 metallisation Methods 0.000 description 1
- 239000004530 micro-emulsion Substances 0.000 description 1
- 239000012046 mixed solvent Substances 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 1
- 125000006501 nitrophenyl group Chemical group 0.000 description 1
- 230000009871 nonspecific binding Effects 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 231100000956 nontoxicity Toxicity 0.000 description 1
- 230000010494 opalescence Effects 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 150000002894 organic compounds Chemical class 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 150000002902 organometallic compounds Chemical class 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 125000005561 phenanthryl group Chemical group 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
- 229920001515 polyalkylene glycol Polymers 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 150000003141 primary amines Chemical class 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 102000004196 processed proteins & peptides Human genes 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- 150000003222 pyridines Chemical class 0.000 description 1
- 125000004076 pyridyl group Chemical group 0.000 description 1
- 125000000168 pyrrolyl group Chemical group 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 238000005057 refrigeration Methods 0.000 description 1
- 230000029058 respiratory gaseous exchange Effects 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 238000007142 ring opening reaction Methods 0.000 description 1
- 150000003335 secondary amines Chemical class 0.000 description 1
- 229910052711 selenium Inorganic materials 0.000 description 1
- SBIBMFFZSBJNJF-UHFFFAOYSA-N selenium;zinc Chemical compound [Se]=[Zn] SBIBMFFZSBJNJF-UHFFFAOYSA-N 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 231100000004 severe toxicity Toxicity 0.000 description 1
- 239000011877 solvent mixture Substances 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 238000006277 sulfonation reaction Methods 0.000 description 1
- 239000011593 sulfur Chemical group 0.000 description 1
- 150000003467 sulfuric acid derivatives Chemical class 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 239000013589 supplement Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- OCGWQDWYSQAFTO-UHFFFAOYSA-N tellanylidenelead Chemical compound [Pb]=[Te] OCGWQDWYSQAFTO-UHFFFAOYSA-N 0.000 description 1
- 229910052714 tellurium Inorganic materials 0.000 description 1
- PORWMNRCUJJQNO-UHFFFAOYSA-N tellurium atom Chemical compound [Te] PORWMNRCUJJQNO-UHFFFAOYSA-N 0.000 description 1
- 238000005979 thermal decomposition reaction Methods 0.000 description 1
- 125000003944 tolyl group Chemical group 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- FKIZDWBGWFWWOV-UHFFFAOYSA-N trimethyl(trimethylsilylselanyl)silane Chemical compound C[Si](C)(C)[Se][Si](C)(C)C FKIZDWBGWFWWOV-UHFFFAOYSA-N 0.000 description 1
- VMDCDZDSJKQVBK-UHFFFAOYSA-N trimethyl(trimethylsilyltellanyl)silane Chemical compound C[Si](C)(C)[Te][Si](C)(C)C VMDCDZDSJKQVBK-UHFFFAOYSA-N 0.000 description 1
- ZAKSIRCIOXDVPT-UHFFFAOYSA-N trioctyl(selanylidene)-$l^{5}-phosphane Chemical compound CCCCCCCCP(=[Se])(CCCCCCCC)CCCCCCCC ZAKSIRCIOXDVPT-UHFFFAOYSA-N 0.000 description 1
- PIOZWDBMINZWGJ-UHFFFAOYSA-N trioctyl(sulfanylidene)-$l^{5}-phosphane Chemical compound CCCCCCCCP(=S)(CCCCCCCC)CCCCCCCC PIOZWDBMINZWGJ-UHFFFAOYSA-N 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- 238000007039 two-step reaction Methods 0.000 description 1
- 230000036325 urinary excretion Effects 0.000 description 1
- 230000006453 vascular barrier function Effects 0.000 description 1
- 238000012800 visualization Methods 0.000 description 1
Images
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K49/00—Preparations for testing in vivo
- A61K49/06—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations
- A61K49/18—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations characterised by a special physical form, e.g. emulsions, microcapsules, liposomes
- A61K49/1818—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations characterised by a special physical form, e.g. emulsions, microcapsules, liposomes particles, e.g. uncoated or non-functionalised microparticles or nanoparticles
- A61K49/1821—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations characterised by a special physical form, e.g. emulsions, microcapsules, liposomes particles, e.g. uncoated or non-functionalised microparticles or nanoparticles coated or functionalised microparticles or nanoparticles
- A61K49/1824—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations characterised by a special physical form, e.g. emulsions, microcapsules, liposomes particles, e.g. uncoated or non-functionalised microparticles or nanoparticles coated or functionalised microparticles or nanoparticles coated or functionalised nanoparticles
- A61K49/1827—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations characterised by a special physical form, e.g. emulsions, microcapsules, liposomes particles, e.g. uncoated or non-functionalised microparticles or nanoparticles coated or functionalised microparticles or nanoparticles coated or functionalised nanoparticles having a (super)(para)magnetic core, being a solid MRI-active material, e.g. magnetite, or composed of a plurality of MRI-active, organic agents, e.g. Gd-chelates, or nuclei, e.g. Eu3+, encapsulated or entrapped in the core of the coated or functionalised nanoparticle
- A61K49/1833—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations characterised by a special physical form, e.g. emulsions, microcapsules, liposomes particles, e.g. uncoated or non-functionalised microparticles or nanoparticles coated or functionalised microparticles or nanoparticles coated or functionalised nanoparticles having a (super)(para)magnetic core, being a solid MRI-active material, e.g. magnetite, or composed of a plurality of MRI-active, organic agents, e.g. Gd-chelates, or nuclei, e.g. Eu3+, encapsulated or entrapped in the core of the coated or functionalised nanoparticle having a (super)(para)magnetic core coated or functionalised with a small organic molecule
- A61K49/1839—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations characterised by a special physical form, e.g. emulsions, microcapsules, liposomes particles, e.g. uncoated or non-functionalised microparticles or nanoparticles coated or functionalised microparticles or nanoparticles coated or functionalised nanoparticles having a (super)(para)magnetic core, being a solid MRI-active material, e.g. magnetite, or composed of a plurality of MRI-active, organic agents, e.g. Gd-chelates, or nuclei, e.g. Eu3+, encapsulated or entrapped in the core of the coated or functionalised nanoparticle having a (super)(para)magnetic core coated or functionalised with a small organic molecule the small organic molecule being a lipid, a fatty acid having 8 or more carbon atoms in the main chain, or a phospholipid
-
- H—ELECTRICITY
- H01—ELECTRIC ELEMENTS
- H01F—MAGNETS; INDUCTANCES; TRANSFORMERS; SELECTION OF MATERIALS FOR THEIR MAGNETIC PROPERTIES
- H01F1/00—Magnets or magnetic bodies characterised by the magnetic materials therefor; Selection of materials for their magnetic properties
- H01F1/0036—Magnets or magnetic bodies characterised by the magnetic materials therefor; Selection of materials for their magnetic properties showing low dimensional magnetism, i.e. spin rearrangements due to a restriction of dimensions, e.g. showing giant magnetoresistivity
- H01F1/0045—Zero dimensional, e.g. nanoparticles, soft nanoparticles for medical/biological use
- H01F1/0054—Coated nanoparticles, e.g. nanoparticles coated with organic surfactant
Abstract
Description
本出願は、2014年9月15日に出願された米国仮特許出願第62/050,477号の優先権を主張し、その全体が、引用により組み込まれる。
本発明は、アメリカ国立衛生研究所からの助成金番号R01 CA126642及びU54 CA151884、アメリカ国立科学財団からの助成金番号CHE−0714189、及びアメリカ陸軍研究事務所からの契約番号W911NF−13−D−0001の下で、政府支援を得てなされたものである。米国政府は、本発明に一定の権利を有する。
本発明は、画像法用途のためのナノ粒子に関する。
ナノメートルサイズの粒子は、多くの場合、その粒子のバルク対応物では達成し得ない興味深い電気的、光学的、磁気的、及び化学的性質を示す。磁性ナノ粒子は、磁気メモリーデバイス、強磁性流体、冷凍システム、医用画像法、薬物ターゲティング、及び触媒作用に用途を見出し得る。磁性酸化物ナノ粒子は、マイクロエマルション及び他の方法を用いて合成し得る。
一態様において、被覆ナノ粒子を製造する方法は、酸を含む溶媒中で化合物を分解して、ナノ粒子を生成させること、該ナノ粒子を試薬を用いて酸化して、酸化ナノ粒子を生成させること、及び該酸化ナノ粒子を双性イオンリガンドで被覆して、該被覆ナノ粒子を生成させること、を含み得る。
磁気共鳴画像法(MRI)は、1980年代に開発されて以来、臨床画像法及び診断において重要な役割を果たしてきており、最近では、生体医学研究ドメインにおいて優れたツールとして役立てられている。例えば、その全体が、引用により組み込まれているGore, J. C.らの文献(Magnetic Resonance Imaging 2011, 29, 587)を参照されたい。30年間の急速かつ着実な進歩の後で、今日においては、T1及びT2強調MRI技術が、高い空間分解能、かなりの組織及び細胞コントラスト、生動物における器官(例えば脳)の機能のイン・サイチュ可視化、並びに三次元的かつ非侵襲的な検出能力という利点を有している。例えば、それぞれその全体が引用により組み込まれている、Na, H. B.; Song, I. C.; Hyeon, T.の文献(Adv. Mater. 2009, 21, 2133−2148);Zhu, D. R.; Liu, F. Y.; Ma, L. N.; Liu, D. J.; Wang, Z. X.の文献(International Journal of Molecular Sciences 2013, 14, 10591)を参照されたい。より最近では、このT1強調MRI研究及び応用は、T1造影剤が、ブリーディングを免れ得る明るいシグナルを示すという理由、又は金属付着及びT1強調MRIが、一般に、T2強調MRIにおいて呼吸又は空気/組織境界によって引き起こされるアーティファクトを減少させることにより、より高い空間分解能を示すという理由で、非常に有望となっている。例えば、その全体が、引用により組み込まれているKim, B. H.; Lee, N.; Kim, H.; An, K.; Park, Y. I.; Choi, Y.; Shin, K.; Lee, Y.; Kwon, S. G.; Na, H. B.; Park, J. G.; Ahn, T. Y.; Kim, Y. W.; Moon, W. K.; Choi, S. H.; Hyeon, T.の文献(Journal of the American Chemical Society 2011, 133, 12624)を参照されたい。水のプロトン緩和時間を変更させることにより、MRIのコントラストを向上させる造影剤の使用は、高コントラストのT1強調MR画像の取得に不可欠である。例えば、その全体が、引用により組み込まれている、Harisinghani, M. G.; Barentsz, J.; Hahn, P. F.; Deserno, W. M.; Tabatabaei, S.; van de Kaa, C. H.; de la Rosette, J.; Weissleder, R.の文献(New England Journal of Medicine 2003, 348, 2491)を参照されたい。
(小さい酸化鉄ナノ粒子)
図1aに示されるように、オレイン酸の存在下、1−テトラデセン、1−ヘキサデセン、及び1−オクタデセンの混合溶媒中で、鉄前駆体(例えば、オレイン酸鉄又は鉄ペンタカルボニル)を分解し、それに続きトリメチルアミンN−オキシドにより酸化することで一連のサイズの単分散酸化鉄ナノ粒子を合成した。溶媒混合物の沸点を、その成分比を変化させて調節することで、反応混合物を、1〜2時間の反応時間、270℃〜300℃の高い温度に保った。結果として生じる疎水性ナノ粒子を、先ず、2−[2−(2−メトキシエトキシ)エトキシ]酢酸(MEAA)とリガンド交換して、ジメチルホルムアミド(DMF)及び水の混合物中での水溶性を確保した。該混合物中で、これらをさらに、ドーパミンスルフォネート(DS)又は双性イオンドーパミンスルフォネート(ZDS)とリガンド交換した。ドーパミンスルフォネート(DS)リガンドもまた、DSが双性イオンではないことを除けば、水への高い溶解性及び酸化鉄表面への強い結合親和性を有する。透過型電子顕微鏡(TEM)画像(図1B〜1E)及びサイズ排除カラムを用いた高速液体クロマトグラフィー(HPLC、図3)により、これらのナノ粒子が、それぞれ7.0、5.5、3.0、2.5nmの無機コアを有すること、及び最小のナノ粒子が、3.0nmの無機コア及び5.0nmのHDを有し得ることが明らかとなった。図2において、ZDS被覆ナノ粒子が、7テスラにおいて11という低いr2/r1比(商業的に入手可能なFeraheme(商標)のr2/r1比よりも2倍低い)、及び0.5テスラ(T)において1.5という低いr2/r1比を有し得ることが示される。このことは、高コントラストのT1強調MR画像法に繋がり得る。承認されたMassachusetts Institute of Technology (MIT)組織内プロトコールに従い、ZDS被覆ナノ粒子を、マウス及びラットに注射し、マウスの尿を一連の時点(図3)で採取し、ラットのT1強調MR画像を取得した(図4)。ZDS被覆ナノ粒子の迅速な腎クリアランスが観察され、注射されたZDS被覆ナノ粒子のサイズは、インビボでは影響を受けなかった(図3)。図4はまた、ラットに注射されたZDS被覆ナノ粒子が、T1コントラスト及び腎クリアランスを示したことを実証した。図4において、赤い丸は、膀胱中の尿におけるZDS被覆ナノ粒子の蓄積を示している。
Claims (23)
- 被覆ナノ粒子を製造する方法であって、
酸を含む溶媒中で化合物を分解して、ナノ粒子を生成させること、
該ナノ粒子を試薬を用いて酸化して、酸化ナノ粒子を生成させること、及び
該酸化ナノ粒子を双性イオンリガンドで被覆して、該被覆ナノ粒子を生成させることを含む、前記方法。 - 前記被覆ナノ粒子が、磁性を有する、請求項1記載の方法。
- 前記酸が、オレイン酸を含む、請求項1記載の方法。
- 前記酸が、ステアリン酸を含む、請求項1記載の方法。
- 前記溶媒が、1−ヘキサデセン、1−オクタデセン、1−エイコセン、1−ドコセン、もしくは1−テトラコサン、又はそれらの混合物を含む、請求項1記載の方法。
- 前記化合物が、オレイン酸鉄を含む、請求項1記載の方法。
- 前記被覆ナノ粒子が、酸化鉄を含む、請求項1記載の方法。
- 前記試薬が、アルキルアミンオキシドを含む、請求項1記載の方法。
- 前記被覆ナノ粒子の流体力学的直径が、5nm〜10nmである、請求項1記載の方法。
- 前記被覆ナノ粒子の無機コアが、2.5nm〜7nmのサイズを有する、請求項1記載の方法。
- 前記被覆ナノ粒子が、5nm未満の流体力学的直径を有する、請求項1記載の方法。
- 前記双性イオンリガンドが、双性イオンドーパミンスルフォネートリガンドを含む、請求項1記載の方法。
- 前記双性イオンリガンドが、ドーパミンスルフォネートリガンドに切り替えられる、請求項1記載の方法。
- ナノ粒子を含む、磁気共鳴画像法又は磁気共鳴血管撮影のためのT1造影剤であって、
該ナノ粒子の無機コアが、2.5〜4nmのサイズを有し、
該ナノ粒子が、5nm未満の流体力学的直径を有し、かつ
該ナノ粒子が、磁性を有する、
前記T1造影剤。 - 前記無機コアが、2.5〜3.5nmのサイズを有する、請求項15記載のT1造影剤。
- 前記ナノ粒子の表面が、双性イオンドーパミンスルフォネートリガンドを含む、請求項15記載のT1造影剤。
- 前記ナノ粒子の表面が、DSリガンドを含む、請求項15記載のT1造影剤。
- 前記ナノ粒子が、酸化鉄を含む、請求項15記載のT1造影剤。
- 磁気共鳴画像法又は磁気共鳴血管撮影のための方法であって、
2.5〜4nmの無機コアを有し、5nm未満の流体力学的直径を有し、かつ磁性を有するナノ粒子を含むT1造影剤を対象に導入すること;及び
該対象の画像信号を生成することを含む、前記方法。 - 前記無機コアが、2.5〜3.5nmのサイズを有する、請求項20記載の方法。
- 前記ナノ粒子の表面が、双性イオンドーパミンスルフォネートリガンドを含む、請求項20記載の方法。
- 前記ナノ粒子の表面が、DSリガンドを含む、請求項20記載の方法。
- 前記ナノ粒子が、酸化鉄を含む、請求項20記載の方法。
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US201462050477P | 2014-09-15 | 2014-09-15 | |
US62/050,477 | 2014-09-15 | ||
PCT/US2015/049524 WO2016044068A2 (en) | 2014-09-15 | 2015-09-10 | Nanoparticles for magnetic resonance imaging applications |
Publications (2)
Publication Number | Publication Date |
---|---|
JP2017529156A true JP2017529156A (ja) | 2017-10-05 |
JP6471227B2 JP6471227B2 (ja) | 2019-02-13 |
Family
ID=54291581
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2017514658A Active JP6471227B2 (ja) | 2014-09-15 | 2015-09-10 | 磁気共鳴画像法用途のためのナノ粒子 |
Country Status (5)
Country | Link |
---|---|
US (2) | US10086094B2 (ja) |
EP (1) | EP3195331B1 (ja) |
JP (1) | JP6471227B2 (ja) |
CA (1) | CA2961358C (ja) |
WO (1) | WO2016044068A2 (ja) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2020138389A1 (ja) * | 2018-12-27 | 2020-07-02 | アステラス製薬株式会社 | ナノ粒子、これを含む磁気共鳴イメージング用造影剤及び双性イオンリガンド化合物 |
Families Citing this family (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CA2961358C (en) * | 2014-09-15 | 2023-08-01 | Massachusetts Institute Of Technology | Nanoparticles for magnetic resonance imaging applications |
CN110799219B (zh) * | 2017-06-28 | 2023-01-06 | 国立研究开发法人理化学研究所 | 纳米颗粒、包含该纳米颗粒的核磁共振成像造影剂、以及配位体化合物 |
CN109432449B (zh) * | 2018-10-19 | 2021-07-30 | 华南师范大学 | 一种铁配合物mri造影剂及其制备方法与应用 |
CN113226990A (zh) | 2018-12-27 | 2021-08-06 | 安斯泰来制药株式会社 | 包含配位结合有一个以上亲水性配体的含有氧化铁的金属粒子的纳米粒子的制造方法 |
WO2020252215A1 (en) * | 2019-06-12 | 2020-12-17 | Cellfe, Inc. | Methods and systems for cell labeling and imaging |
CN116327983A (zh) * | 2023-03-15 | 2023-06-27 | 新乡医学院 | 一种奶酪形多孔结构纳米氧化锰造影剂的制备方法及应用 |
Citations (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2007269770A (ja) * | 2006-03-09 | 2007-10-18 | Mitsubishi Chemicals Corp | 機能性磁気超ナノ微粒子及びその用途 |
JP2010518070A (ja) * | 2007-02-07 | 2010-05-27 | スパーゴ・イメージング・アー・ベー | コーティングされた造影剤を使用することによる生体物質の可視化 |
US20130184444A1 (en) * | 2011-12-16 | 2013-07-18 | Massachusetts Institute Of Technology | Compact nanoparticles for biological applications |
JP2013534893A (ja) * | 2010-08-05 | 2013-09-09 | ハンファ ケミカル コーポレーション | 極小かつ均一な大きさの酸化鉄系常磁性ナノ粒子の製造方法及びこれを用いるmrit1造影剤 |
JP6063627B2 (ja) * | 2008-12-29 | 2017-01-18 | ゼネラル・エレクトリック・カンパニイ | 診断イメージング用のナノ粒子造影剤 |
US10086094B2 (en) * | 2014-09-15 | 2018-10-02 | Massachusetts Institute Of Technology | Nanoparticles for magnetic resonance imaging applications |
Family Cites Families (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6322901B1 (en) | 1997-11-13 | 2001-11-27 | Massachusetts Institute Of Technology | Highly luminescent color-selective nano-crystalline materials |
US6251303B1 (en) | 1998-09-18 | 2001-06-26 | Massachusetts Institute Of Technology | Water-soluble fluorescent nanocrystals |
US6576291B2 (en) | 2000-12-08 | 2003-06-10 | Massachusetts Institute Of Technology | Preparation of nanocrystallites |
US8574549B2 (en) * | 2008-12-29 | 2013-11-05 | General Electric Company | Nanoparticle contrast agents for diagnostic imaging |
KR101263732B1 (ko) * | 2011-01-28 | 2013-05-14 | 한국과학기술연구원 | 암 조직으로의 전달 비율이 높은 바이오-이미지용 나노입자 |
-
2015
- 2015-09-10 CA CA2961358A patent/CA2961358C/en active Active
- 2015-09-10 JP JP2017514658A patent/JP6471227B2/ja active Active
- 2015-09-10 WO PCT/US2015/049524 patent/WO2016044068A2/en active Application Filing
- 2015-09-10 EP EP15778408.3A patent/EP3195331B1/en active Active
- 2015-09-11 US US14/852,432 patent/US10086094B2/en active Active
-
2018
- 2018-10-01 US US16/149,082 patent/US10758633B2/en active Active
Patent Citations (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2007269770A (ja) * | 2006-03-09 | 2007-10-18 | Mitsubishi Chemicals Corp | 機能性磁気超ナノ微粒子及びその用途 |
JP2010518070A (ja) * | 2007-02-07 | 2010-05-27 | スパーゴ・イメージング・アー・ベー | コーティングされた造影剤を使用することによる生体物質の可視化 |
JP6063627B2 (ja) * | 2008-12-29 | 2017-01-18 | ゼネラル・エレクトリック・カンパニイ | 診断イメージング用のナノ粒子造影剤 |
JP2013534893A (ja) * | 2010-08-05 | 2013-09-09 | ハンファ ケミカル コーポレーション | 極小かつ均一な大きさの酸化鉄系常磁性ナノ粒子の製造方法及びこれを用いるmrit1造影剤 |
US20130184444A1 (en) * | 2011-12-16 | 2013-07-18 | Massachusetts Institute Of Technology | Compact nanoparticles for biological applications |
US10086094B2 (en) * | 2014-09-15 | 2018-10-02 | Massachusetts Institute Of Technology | Nanoparticles for magnetic resonance imaging applications |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2020138389A1 (ja) * | 2018-12-27 | 2020-07-02 | アステラス製薬株式会社 | ナノ粒子、これを含む磁気共鳴イメージング用造影剤及び双性イオンリガンド化合物 |
Also Published As
Publication number | Publication date |
---|---|
US20160074538A1 (en) | 2016-03-17 |
CA2961358C (en) | 2023-08-01 |
US10758633B2 (en) | 2020-09-01 |
EP3195331A2 (en) | 2017-07-26 |
US20190022258A1 (en) | 2019-01-24 |
WO2016044068A3 (en) | 2016-05-12 |
EP3195331B1 (en) | 2021-05-26 |
WO2016044068A2 (en) | 2016-03-24 |
US10086094B2 (en) | 2018-10-02 |
JP6471227B2 (ja) | 2019-02-13 |
CA2961358A1 (en) | 2016-03-24 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP6471227B2 (ja) | 磁気共鳴画像法用途のためのナノ粒子 | |
Wu et al. | Designed synthesis and surface engineering strategies of magnetic iron oxide nanoparticles for biomedical applications | |
Das et al. | Tailor made magnetic nanolights: Fabrication to cancer theranostics applications | |
Colombo et al. | Biological applications of magnetic nanoparticles | |
Lee et al. | Designed synthesis of uniformly sized iron oxide nanoparticles for efficient magnetic resonance imaging contrast agents | |
Prakash et al. | Bilayers as phase transfer agents for nanocrystals prepared in nonpolar solvents | |
Selvan | Silica-coated quantum dots and magnetic nanoparticles for bioimaging applications (Mini-Review) | |
US9078920B2 (en) | Compact nanoparticles for biological applications | |
Pahari et al. | Magneto-fluorescent yolk–shell nanoparticles | |
US20120114564A1 (en) | Mri t1 contrasting agent comprising manganese oxide nanoparticle | |
JPWO2009014201A1 (ja) | 表面被覆無機物粒子の製造方法 | |
US20120201760A1 (en) | Metal oxide particles coated with polyethylene glycol and their synthesis | |
Bakalova et al. | Multimodal silica-shelled quantum dots: direct intracellular delivery, photosensitization, toxic, and microcirculation effects | |
Chen et al. | Preparation and control of the formation of single core and clustered nanoparticles for biomedical applications using a versatile amphiphilic diblock copolymer | |
Jang et al. | In vivo magnetic resonance and fluorescence dual imaging of tumor sites by using dye-doped silica-coated iron oxide nanoparticles | |
WO2014081322A1 (en) | Superparamagnetic iron oxide nanoparticles with ultra-thin polymer layers, the method of their preparation and application | |
Huang et al. | Fluorescent-magnetic multifunctional nanoparticles for imaging and drug delivery | |
US20150079006A1 (en) | Iron oxide nanocomposite, magnetic resonance imaging t2 contrast medium comprising same, and method for manufacturing same | |
Varanda et al. | Inorganic and organic–inorganic composite nanoparticles with potential biomedical applications: synthesis challenges for enhanced performance | |
Bordeianu et al. | How a grafting anchor tailors the cellular uptake and in vivo fate of dendronized iron oxide nanoparticles | |
Poon et al. | Tuneable manganese oxide nanoparticle based theranostic agents for potential diagnosis and drug delivery | |
US20200023084A1 (en) | Tiny nanoparticles for magnetic resonance imaging applications | |
Pardo et al. | Analysis of the influence of synthetic paramaters on the structure and physico-chemical properties of non-spherical iron oxide nanocrystals and their biological stability and compatibility | |
Li et al. | Phase Transfer of Hydrophobic Nanoparticles Using a Zwitterionic Sulfobetaine Siloxane Generates Highly Biocompatible and Compact Surfaces | |
WO2019004297A1 (ja) | ナノ粒子、これを含む磁気共鳴イメージング用造影剤及びリガンド化合物 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20170807 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20180313 |
|
A977 | Report on retrieval |
Free format text: JAPANESE INTERMEDIATE CODE: A971007 Effective date: 20180314 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20180607 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20180912 |
|
TRDD | Decision of grant or rejection written | ||
A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20181225 |
|
A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20190121 |
|
R150 | Certificate of patent or registration of utility model |
Ref document number: 6471227 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
R157 | Certificate of patent or utility model (correction) |
Free format text: JAPANESE INTERMEDIATE CODE: R157 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |