JP5667180B2 - 哺乳類の有核細胞に由来するマイクロベシクル及びその用途 - Google Patents
哺乳類の有核細胞に由来するマイクロベシクル及びその用途 Download PDFInfo
- Publication number
- JP5667180B2 JP5667180B2 JP2012518496A JP2012518496A JP5667180B2 JP 5667180 B2 JP5667180 B2 JP 5667180B2 JP 2012518496 A JP2012518496 A JP 2012518496A JP 2012518496 A JP2012518496 A JP 2012518496A JP 5667180 B2 JP5667180 B2 JP 5667180B2
- Authority
- JP
- Japan
- Prior art keywords
- cells
- cell
- microvesicles
- microvesicle
- loaded
- 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.)
- Active
Links
- 210000004027 cell Anatomy 0.000 claims description 586
- 239000000126 substance Substances 0.000 claims description 234
- 238000000034 method Methods 0.000 claims description 122
- 230000001225 therapeutic effect Effects 0.000 claims description 109
- 210000005087 mononuclear cell Anatomy 0.000 claims description 85
- 201000010099 disease Diseases 0.000 claims description 68
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 68
- 210000000170 cell membrane Anatomy 0.000 claims description 58
- 238000001125 extrusion Methods 0.000 claims description 54
- 210000002540 macrophage Anatomy 0.000 claims description 51
- 239000000725 suspension Substances 0.000 claims description 42
- 238000004519 manufacturing process Methods 0.000 claims description 40
- 239000012528 membrane Substances 0.000 claims description 30
- 239000000203 mixture Substances 0.000 claims description 28
- 238000003745 diagnosis Methods 0.000 claims description 27
- 108020004707 nucleic acids Proteins 0.000 claims description 22
- 102000039446 nucleic acids Human genes 0.000 claims description 22
- 150000007523 nucleic acids Chemical class 0.000 claims description 22
- 239000002245 particle Substances 0.000 claims description 20
- 238000011068 loading method Methods 0.000 claims description 18
- 239000008194 pharmaceutical composition Substances 0.000 claims description 18
- 241000124008 Mammalia Species 0.000 claims description 17
- 239000002202 Polyethylene glycol Substances 0.000 claims description 15
- 229920001223 polyethylene glycol Polymers 0.000 claims description 15
- 229920000858 Cyclodextrin Polymers 0.000 claims description 14
- HFHDHCJBZVLPGP-UHFFFAOYSA-N schardinger α-dextrin Chemical group O1C(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(O)C2O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC2C(O)C(O)C1OC2CO HFHDHCJBZVLPGP-UHFFFAOYSA-N 0.000 claims description 14
- 230000000692 anti-sense effect Effects 0.000 claims description 12
- 238000012258 culturing Methods 0.000 claims description 10
- 230000008569 process Effects 0.000 claims description 8
- 239000000523 sample Substances 0.000 claims description 6
- 210000004962 mammalian cell Anatomy 0.000 claims description 4
- AOJJSUZBOXZQNB-TZSSRYMLSA-N Doxorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 AOJJSUZBOXZQNB-TZSSRYMLSA-N 0.000 description 316
- 229960004679 doxorubicin Drugs 0.000 description 157
- 210000001519 tissue Anatomy 0.000 description 132
- 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 83
- 239000002953 phosphate buffered saline Substances 0.000 description 83
- 206010028980 Neoplasm Diseases 0.000 description 73
- 201000011510 cancer Diseases 0.000 description 70
- 238000011282 treatment Methods 0.000 description 55
- 239000000243 solution Substances 0.000 description 54
- 108010064593 Intercellular Adhesion Molecule-1 Proteins 0.000 description 52
- 102000015271 Intercellular Adhesion Molecule-1 Human genes 0.000 description 52
- 108090000623 proteins and genes Proteins 0.000 description 48
- 102000004169 proteins and genes Human genes 0.000 description 42
- 235000018102 proteins Nutrition 0.000 description 39
- 239000003814 drug Substances 0.000 description 36
- 238000005406 washing Methods 0.000 description 35
- 241000699670 Mus sp. Species 0.000 description 34
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 33
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 33
- 229940079593 drug Drugs 0.000 description 33
- MZOFCQQQCNRIBI-VMXHOPILSA-N (3s)-4-[[(2s)-1-[[(2s)-1-[[(1s)-1-carboxy-2-hydroxyethyl]amino]-4-methyl-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-3-[[2-[[(2s)-2,6-diaminohexanoyl]amino]acetyl]amino]-4-oxobutanoic acid Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CC(O)=O)NC(=O)CNC(=O)[C@@H](N)CCCCN MZOFCQQQCNRIBI-VMXHOPILSA-N 0.000 description 31
- 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 description 31
- 239000002246 antineoplastic agent Substances 0.000 description 27
- 108010052285 Membrane Proteins Proteins 0.000 description 26
- 239000002096 quantum dot Substances 0.000 description 24
- 108010064548 Lymphocyte Function-Associated Antigen-1 Proteins 0.000 description 23
- 102000018697 Membrane Proteins Human genes 0.000 description 23
- 210000001185 bone marrow Anatomy 0.000 description 23
- SDZRWUKZFQQKKV-JHADDHBZSA-N cytochalasin D Chemical compound C([C@H]1[C@@H]2[C@@H](C([C@@H](O)[C@H]\3[C@]2([C@@H](/C=C/[C@@](C)(O)C(=O)[C@@H](C)C/C=C/3)OC(C)=O)C(=O)N1)=C)C)C1=CC=CC=C1 SDZRWUKZFQQKKV-JHADDHBZSA-N 0.000 description 22
- 241000699666 Mus <mouse, genus> Species 0.000 description 20
- UQSXHKLRYXJYBZ-UHFFFAOYSA-N Iron oxide Chemical compound [Fe]=O UQSXHKLRYXJYBZ-UHFFFAOYSA-N 0.000 description 18
- 108090000631 Trypsin Proteins 0.000 description 18
- 102000004142 Trypsin Human genes 0.000 description 18
- 210000004204 blood vessel Anatomy 0.000 description 18
- 239000012588 trypsin Substances 0.000 description 18
- 230000006907 apoptotic process Effects 0.000 description 17
- 230000005540 biological transmission Effects 0.000 description 17
- 239000002609 medium Substances 0.000 description 17
- 238000000354 decomposition reaction Methods 0.000 description 16
- 230000000694 effects Effects 0.000 description 16
- 229940041181 antineoplastic drug Drugs 0.000 description 15
- 238000004520 electroporation Methods 0.000 description 15
- 239000003656 tris buffered saline Substances 0.000 description 15
- 239000006059 cover glass Substances 0.000 description 14
- 230000001965 increasing effect Effects 0.000 description 14
- 239000002105 nanoparticle Substances 0.000 description 14
- 230000027455 binding Effects 0.000 description 13
- 238000001727 in vivo Methods 0.000 description 13
- 238000012545 processing Methods 0.000 description 13
- 210000003556 vascular endothelial cell Anatomy 0.000 description 13
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 12
- 108091008605 VEGF receptors Proteins 0.000 description 12
- 108010073929 Vascular Endothelial Growth Factor A Proteins 0.000 description 12
- 102000009484 Vascular Endothelial Growth Factor Receptors Human genes 0.000 description 12
- 102000005789 Vascular Endothelial Growth Factors Human genes 0.000 description 12
- 108010019530 Vascular Endothelial Growth Factors Proteins 0.000 description 12
- 210000004692 intercellular junction Anatomy 0.000 description 12
- 108090000765 processed proteins & peptides Proteins 0.000 description 12
- 206010009944 Colon cancer Diseases 0.000 description 11
- 206010061218 Inflammation Diseases 0.000 description 11
- 239000013504 Triton X-100 Substances 0.000 description 11
- 229920004890 Triton X-100 Polymers 0.000 description 11
- 239000002158 endotoxin Substances 0.000 description 11
- 230000004054 inflammatory process Effects 0.000 description 11
- 229920006008 lipopolysaccharide Polymers 0.000 description 11
- 238000012546 transfer Methods 0.000 description 11
- 238000003917 TEM image Methods 0.000 description 10
- 210000004369 blood Anatomy 0.000 description 10
- 239000008280 blood Substances 0.000 description 10
- 239000002502 liposome Substances 0.000 description 10
- 108091064282 miR-125 stem-loop Proteins 0.000 description 10
- 108091037066 miR-125-1 stem-loop Proteins 0.000 description 10
- 108091062107 miR-125-2 stem-loop Proteins 0.000 description 10
- 108091079767 miR-125-3 stem-loop Proteins 0.000 description 10
- 210000003462 vein Anatomy 0.000 description 10
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 10
- 230000005907 cancer growth Effects 0.000 description 9
- 229960004562 carboplatin Drugs 0.000 description 9
- 190000008236 carboplatin Chemical compound 0.000 description 9
- 230000006037 cell lysis Effects 0.000 description 9
- 108020001507 fusion proteins Proteins 0.000 description 9
- 102000037865 fusion proteins Human genes 0.000 description 9
- 238000000265 homogenisation Methods 0.000 description 9
- 239000011148 porous material Substances 0.000 description 9
- 102000004196 processed proteins & peptides Human genes 0.000 description 9
- 230000002829 reductive effect Effects 0.000 description 9
- 238000000527 sonication Methods 0.000 description 9
- 210000005167 vascular cell Anatomy 0.000 description 9
- 102000004889 Interleukin-6 Human genes 0.000 description 8
- 108090001005 Interleukin-6 Proteins 0.000 description 8
- 108700011259 MicroRNAs Proteins 0.000 description 8
- 108020002230 Pancreatic Ribonuclease Proteins 0.000 description 8
- 102000005891 Pancreatic ribonuclease Human genes 0.000 description 8
- 239000002260 anti-inflammatory agent Substances 0.000 description 8
- 230000015556 catabolic process Effects 0.000 description 8
- 208000029742 colonic neoplasm Diseases 0.000 description 8
- 239000002299 complementary DNA Substances 0.000 description 8
- 238000006731 degradation reaction Methods 0.000 description 8
- 210000004443 dendritic cell Anatomy 0.000 description 8
- 239000011521 glass Substances 0.000 description 8
- 230000006698 induction Effects 0.000 description 8
- 150000002632 lipids Chemical class 0.000 description 8
- 239000002679 microRNA Substances 0.000 description 8
- 210000002966 serum Anatomy 0.000 description 8
- 210000000130 stem cell Anatomy 0.000 description 8
- 239000003053 toxin Substances 0.000 description 8
- 231100000765 toxin Toxicity 0.000 description 8
- 108700012359 toxins Proteins 0.000 description 8
- 101800003838 Epidermal growth factor Proteins 0.000 description 7
- 102400001368 Epidermal growth factor Human genes 0.000 description 7
- 108010010803 Gelatin Proteins 0.000 description 7
- 239000000232 Lipid Bilayer Substances 0.000 description 7
- 206010058467 Lung neoplasm malignant Diseases 0.000 description 7
- BQRGNLJZBFXNCZ-UHFFFAOYSA-N calcein am Chemical compound O1C(=O)C2=CC=CC=C2C21C1=CC(CN(CC(=O)OCOC(C)=O)CC(=O)OCOC(C)=O)=C(OC(C)=O)C=C1OC1=C2C=C(CN(CC(=O)OCOC(C)=O)CC(=O)OCOC(=O)C)C(OC(C)=O)=C1 BQRGNLJZBFXNCZ-UHFFFAOYSA-N 0.000 description 7
- 238000012377 drug delivery Methods 0.000 description 7
- 229940116977 epidermal growth factor Drugs 0.000 description 7
- 210000003743 erythrocyte Anatomy 0.000 description 7
- 239000008273 gelatin Substances 0.000 description 7
- 229920000159 gelatin Polymers 0.000 description 7
- 235000019322 gelatine Nutrition 0.000 description 7
- 235000011852 gelatine desserts Nutrition 0.000 description 7
- SDUQYLNIPVEERB-QPPQHZFASA-N gemcitabine Chemical compound O=C1N=C(N)C=CN1[C@H]1C(F)(F)[C@H](O)[C@@H](CO)O1 SDUQYLNIPVEERB-QPPQHZFASA-N 0.000 description 7
- 229960005277 gemcitabine Drugs 0.000 description 7
- 239000005090 green fluorescent protein Substances 0.000 description 7
- 238000011534 incubation Methods 0.000 description 7
- 208000027866 inflammatory disease Diseases 0.000 description 7
- 201000005202 lung cancer Diseases 0.000 description 7
- 208000020816 lung neoplasm Diseases 0.000 description 7
- 239000012188 paraffin wax Substances 0.000 description 7
- VBEQCZHXXJYVRD-GACYYNSASA-N uroanthelone Chemical compound C([C@@H](C(=O)N[C@H](C(=O)N[C@@H](CS)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CS)C(=O)N[C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O)C(C)C)[C@@H](C)O)NC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CCSC)NC(=O)[C@H](CS)NC(=O)[C@@H](NC(=O)CNC(=O)CNC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CS)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CS)NC(=O)CNC(=O)[C@H]1N(CCC1)C(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC(N)=O)C(C)C)[C@@H](C)CC)C1=CC=C(O)C=C1 VBEQCZHXXJYVRD-GACYYNSASA-N 0.000 description 7
- YBJHBAHKTGYVGT-ZKWXMUAHSA-N (+)-Biotin Chemical compound N1C(=O)N[C@@H]2[C@H](CCCCC(=O)O)SC[C@@H]21 YBJHBAHKTGYVGT-ZKWXMUAHSA-N 0.000 description 6
- 102000004127 Cytokines Human genes 0.000 description 6
- 108090000695 Cytokines Proteins 0.000 description 6
- 239000011324 bead Substances 0.000 description 6
- 238000006243 chemical reaction Methods 0.000 description 6
- 230000002354 daily effect Effects 0.000 description 6
- 229960003957 dexamethasone Drugs 0.000 description 6
- UREBDLICKHMUKA-CXSFZGCWSA-N dexamethasone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@@H](C)[C@@](C(=O)CO)(O)[C@@]1(C)C[C@@H]2O UREBDLICKHMUKA-CXSFZGCWSA-N 0.000 description 6
- 238000002296 dynamic light scattering Methods 0.000 description 6
- 210000002216 heart Anatomy 0.000 description 6
- 238000000338 in vitro Methods 0.000 description 6
- 201000001441 melanoma Diseases 0.000 description 6
- 230000028327 secretion Effects 0.000 description 6
- 230000009466 transformation Effects 0.000 description 6
- 238000005199 ultracentrifugation Methods 0.000 description 6
- 102000007469 Actins Human genes 0.000 description 5
- 108010085238 Actins Proteins 0.000 description 5
- 239000004037 angiogenesis inhibitor Substances 0.000 description 5
- 229940121369 angiogenesis inhibitor Drugs 0.000 description 5
- 230000001093 anti-cancer Effects 0.000 description 5
- 229940121363 anti-inflammatory agent Drugs 0.000 description 5
- 239000000872 buffer Substances 0.000 description 5
- 239000003636 conditioned culture medium Substances 0.000 description 5
- 230000007423 decrease Effects 0.000 description 5
- 238000010586 diagram Methods 0.000 description 5
- 108091006047 fluorescent proteins Proteins 0.000 description 5
- 102000034287 fluorescent proteins Human genes 0.000 description 5
- 230000012010 growth Effects 0.000 description 5
- 230000002757 inflammatory effect Effects 0.000 description 5
- 238000002347 injection Methods 0.000 description 5
- 239000007924 injection Substances 0.000 description 5
- 210000004072 lung Anatomy 0.000 description 5
- 239000011859 microparticle Substances 0.000 description 5
- 239000013612 plasmid Substances 0.000 description 5
- 230000008685 targeting Effects 0.000 description 5
- 208000019553 vascular disease Diseases 0.000 description 5
- WMBWREPUVVBILR-WIYYLYMNSA-N (-)-Epigallocatechin-3-o-gallate Chemical compound O([C@@H]1CC2=C(O)C=C(C=C2O[C@@H]1C=1C=C(O)C(O)=C(O)C=1)O)C(=O)C1=CC(O)=C(O)C(O)=C1 WMBWREPUVVBILR-WIYYLYMNSA-N 0.000 description 4
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 4
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 4
- 108020004414 DNA Proteins 0.000 description 4
- GHASVSINZRGABV-UHFFFAOYSA-N Fluorouracil Chemical compound FC1=CNC(=O)NC1=O GHASVSINZRGABV-UHFFFAOYSA-N 0.000 description 4
- WMBWREPUVVBILR-UHFFFAOYSA-N GCG Natural products C=1C(O)=C(O)C(O)=CC=1C1OC2=CC(O)=CC(O)=C2CC1OC(=O)C1=CC(O)=C(O)C(O)=C1 WMBWREPUVVBILR-UHFFFAOYSA-N 0.000 description 4
- 101001012157 Homo sapiens Receptor tyrosine-protein kinase erbB-2 Proteins 0.000 description 4
- 206010027476 Metastases Diseases 0.000 description 4
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 4
- 229930040373 Paraformaldehyde Natural products 0.000 description 4
- 102100024616 Platelet endothelial cell adhesion molecule Human genes 0.000 description 4
- 102100030086 Receptor tyrosine-protein kinase erbB-2 Human genes 0.000 description 4
- 108091008874 T cell receptors Proteins 0.000 description 4
- 102000016266 T-Cell Antigen Receptors Human genes 0.000 description 4
- GLNADSQYFUSGOU-GPTZEZBUSA-J Trypan blue Chemical compound [Na+].[Na+].[Na+].[Na+].C1=C(S([O-])(=O)=O)C=C2C=C(S([O-])(=O)=O)C(/N=N/C3=CC=C(C=C3C)C=3C=C(C(=CC=3)\N=N\C=3C(=CC4=CC(=CC(N)=C4C=3O)S([O-])(=O)=O)S([O-])(=O)=O)C)=C(O)C2=C1N GLNADSQYFUSGOU-GPTZEZBUSA-J 0.000 description 4
- 108010000134 Vascular Cell Adhesion Molecule-1 Proteins 0.000 description 4
- 102100023543 Vascular cell adhesion protein 1 Human genes 0.000 description 4
- RJURFGZVJUQBHK-UHFFFAOYSA-N actinomycin D Natural products CC1OC(=O)C(C(C)C)N(C)C(=O)CN(C)C(=O)C2CCCN2C(=O)C(C(C)C)NC(=O)C1NC(=O)C1=C(N)C(=O)C(C)=C2OC(C(C)=CC=C3C(=O)NC4C(=O)NC(C(N5CCCC5C(=O)N(C)CC(=O)N(C)C(C(C)C)C(=O)OC4C)=O)C(C)C)=C3N=C21 RJURFGZVJUQBHK-UHFFFAOYSA-N 0.000 description 4
- 210000000988 bone and bone Anatomy 0.000 description 4
- DEGAKNSWVGKMLS-UHFFFAOYSA-N calcein Chemical compound O1C(=O)C2=CC=CC=C2C21C1=CC(CN(CC(O)=O)CC(O)=O)=C(O)C=C1OC1=C2C=C(CN(CC(O)=O)CC(=O)O)C(O)=C1 DEGAKNSWVGKMLS-UHFFFAOYSA-N 0.000 description 4
- 238000005119 centrifugation Methods 0.000 description 4
- 230000003247 decreasing effect Effects 0.000 description 4
- 238000011161 development Methods 0.000 description 4
- 238000002474 experimental method Methods 0.000 description 4
- 238000001943 fluorescence-activated cell sorting Methods 0.000 description 4
- 229960002949 fluorouracil Drugs 0.000 description 4
- 230000028993 immune response Effects 0.000 description 4
- 238000003364 immunohistochemistry Methods 0.000 description 4
- 239000000411 inducer Substances 0.000 description 4
- 230000005764 inhibitory process Effects 0.000 description 4
- 210000000265 leukocyte Anatomy 0.000 description 4
- 239000003550 marker Substances 0.000 description 4
- 239000000463 material Substances 0.000 description 4
- 230000034217 membrane fusion Effects 0.000 description 4
- 230000009401 metastasis Effects 0.000 description 4
- 229960002378 oftasceine Drugs 0.000 description 4
- 230000036407 pain Effects 0.000 description 4
- 229920002866 paraformaldehyde Polymers 0.000 description 4
- 239000012679 serum free medium Substances 0.000 description 4
- 239000001509 sodium citrate Substances 0.000 description 4
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 4
- 239000000758 substrate Substances 0.000 description 4
- 230000004083 survival effect Effects 0.000 description 4
- 239000008096 xylene Substances 0.000 description 4
- BGWLYQZDNFIFRX-UHFFFAOYSA-N 5-[3-[2-[3-(3,8-diamino-6-phenylphenanthridin-5-ium-5-yl)propylamino]ethylamino]propyl]-6-phenylphenanthridin-5-ium-3,8-diamine;dichloride Chemical compound [Cl-].[Cl-].C=1C(N)=CC=C(C2=CC=C(N)C=C2[N+]=2CCCNCCNCCC[N+]=3C4=CC(N)=CC=C4C4=CC=C(N)C=C4C=3C=3C=CC=CC=3)C=1C=2C1=CC=CC=C1 BGWLYQZDNFIFRX-UHFFFAOYSA-N 0.000 description 3
- 206010006187 Breast cancer Diseases 0.000 description 3
- 208000026310 Breast neoplasm Diseases 0.000 description 3
- 101100289995 Caenorhabditis elegans mac-1 gene Proteins 0.000 description 3
- 208000001333 Colorectal Neoplasms Diseases 0.000 description 3
- 102000004190 Enzymes Human genes 0.000 description 3
- 108090000790 Enzymes Proteins 0.000 description 3
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 3
- 108010043121 Green Fluorescent Proteins Proteins 0.000 description 3
- 229930012538 Paclitaxel Natural products 0.000 description 3
- 206010061902 Pancreatic neoplasm Diseases 0.000 description 3
- 108091093037 Peptide nucleic acid Proteins 0.000 description 3
- 210000001744 T-lymphocyte Anatomy 0.000 description 3
- 229940124599 anti-inflammatory drug Drugs 0.000 description 3
- 239000000427 antigen Substances 0.000 description 3
- 108091007433 antigens Proteins 0.000 description 3
- 102000036639 antigens Human genes 0.000 description 3
- 230000001640 apoptogenic effect Effects 0.000 description 3
- 229960002685 biotin Drugs 0.000 description 3
- 235000020958 biotin Nutrition 0.000 description 3
- 239000011616 biotin Substances 0.000 description 3
- 210000002798 bone marrow cell Anatomy 0.000 description 3
- 239000006285 cell suspension Substances 0.000 description 3
- 230000001413 cellular effect Effects 0.000 description 3
- 210000003850 cellular structure Anatomy 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- 239000011248 coating agent Substances 0.000 description 3
- 238000000576 coating method Methods 0.000 description 3
- 238000012790 confirmation Methods 0.000 description 3
- 230000006378 damage Effects 0.000 description 3
- 230000034994 death Effects 0.000 description 3
- 238000000502 dialysis Methods 0.000 description 3
- 239000002552 dosage form Substances 0.000 description 3
- 229940088598 enzyme Drugs 0.000 description 3
- 238000001914 filtration Methods 0.000 description 3
- 239000003102 growth factor Substances 0.000 description 3
- 210000002865 immune cell Anatomy 0.000 description 3
- 230000008105 immune reaction Effects 0.000 description 3
- 239000003112 inhibitor Substances 0.000 description 3
- 230000002147 killing effect Effects 0.000 description 3
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 description 3
- 238000005259 measurement Methods 0.000 description 3
- 210000002901 mesenchymal stem cell Anatomy 0.000 description 3
- 230000002503 metabolic effect Effects 0.000 description 3
- 208000037819 metastatic cancer Diseases 0.000 description 3
- 208000011575 metastatic malignant neoplasm Diseases 0.000 description 3
- 210000001616 monocyte Anatomy 0.000 description 3
- 229960001592 paclitaxel Drugs 0.000 description 3
- 201000002528 pancreatic cancer Diseases 0.000 description 3
- 208000008443 pancreatic carcinoma Diseases 0.000 description 3
- 238000000746 purification Methods 0.000 description 3
- 238000000926 separation method Methods 0.000 description 3
- 210000000952 spleen Anatomy 0.000 description 3
- 238000010186 staining Methods 0.000 description 3
- 238000007920 subcutaneous administration Methods 0.000 description 3
- 208000011580 syndromic disease Diseases 0.000 description 3
- RCINICONZNJXQF-MZXODVADSA-N taxol Chemical compound O([C@@H]1[C@@]2(C[C@@H](C(C)=C(C2(C)C)[C@H](C([C@]2(C)[C@@H](O)C[C@H]3OC[C@]3([C@H]21)OC(C)=O)=O)OC(=O)C)OC(=O)[C@H](O)[C@@H](NC(=O)C=1C=CC=CC=1)C=1C=CC=CC=1)O)C(=O)C1=CC=CC=C1 RCINICONZNJXQF-MZXODVADSA-N 0.000 description 3
- 229940124597 therapeutic agent Drugs 0.000 description 3
- 231100000331 toxic Toxicity 0.000 description 3
- 230000002588 toxic effect Effects 0.000 description 3
- 230000002792 vascular Effects 0.000 description 3
- VEEGZPWAAPPXRB-BJMVGYQFSA-N (3e)-3-(1h-imidazol-5-ylmethylidene)-1h-indol-2-one Chemical compound O=C1NC2=CC=CC=C2\C1=C/C1=CN=CN1 VEEGZPWAAPPXRB-BJMVGYQFSA-N 0.000 description 2
- WRGQSWVCFNIUNZ-GDCKJWNLSA-N 1-oleoyl-sn-glycerol 3-phosphate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OC[C@@H](O)COP(O)(O)=O WRGQSWVCFNIUNZ-GDCKJWNLSA-N 0.000 description 2
- STQGQHZAVUOBTE-UHFFFAOYSA-N 7-Cyan-hept-2t-en-4,6-diinsaeure Natural products C1=2C(O)=C3C(=O)C=4C(OC)=CC=CC=4C(=O)C3=C(O)C=2CC(O)(C(C)=O)CC1OC1CC(N)C(O)C(C)O1 STQGQHZAVUOBTE-UHFFFAOYSA-N 0.000 description 2
- 108020005544 Antisense RNA Proteins 0.000 description 2
- 206010003210 Arteriosclerosis Diseases 0.000 description 2
- 108010006654 Bleomycin Proteins 0.000 description 2
- 108010022366 Carcinoembryonic Antigen Proteins 0.000 description 2
- 102100025475 Carcinoembryonic antigen-related cell adhesion molecule 5 Human genes 0.000 description 2
- 201000009030 Carcinoma Diseases 0.000 description 2
- DLGOEMSEDOSKAD-UHFFFAOYSA-N Carmustine Chemical compound ClCCNC(=O)N(N=O)CCCl DLGOEMSEDOSKAD-UHFFFAOYSA-N 0.000 description 2
- 206010008342 Cervix carcinoma Diseases 0.000 description 2
- PHEDXBVPIONUQT-UHFFFAOYSA-N Cocarcinogen A1 Natural products CCCCCCCCCCCCCC(=O)OC1C(C)C2(O)C3C=C(C)C(=O)C3(O)CC(CO)=CC2C2C1(OC(C)=O)C2(C)C PHEDXBVPIONUQT-UHFFFAOYSA-N 0.000 description 2
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 2
- 108010092160 Dactinomycin Proteins 0.000 description 2
- 238000009007 Diagnostic Kit Methods 0.000 description 2
- 102000015689 E-Selectin Human genes 0.000 description 2
- 108010024212 E-Selectin Proteins 0.000 description 2
- 102000001301 EGF receptor Human genes 0.000 description 2
- 108060006698 EGF receptor Proteins 0.000 description 2
- 206010018364 Glomerulonephritis Diseases 0.000 description 2
- GRRNUXAQVGOGFE-UHFFFAOYSA-N Hygromycin-B Natural products OC1C(NC)CC(N)C(O)C1OC1C2OC3(C(C(O)C(O)C(C(N)CO)O3)O)OC2C(O)C(CO)O1 GRRNUXAQVGOGFE-UHFFFAOYSA-N 0.000 description 2
- 238000012404 In vitro experiment Methods 0.000 description 2
- 102100037850 Interferon gamma Human genes 0.000 description 2
- 108010074328 Interferon-gamma Proteins 0.000 description 2
- 108010002352 Interleukin-1 Proteins 0.000 description 2
- 108090000174 Interleukin-10 Proteins 0.000 description 2
- GQYIWUVLTXOXAJ-UHFFFAOYSA-N Lomustine Chemical compound ClCCN(N=O)C(=O)NC1CCCCC1 GQYIWUVLTXOXAJ-UHFFFAOYSA-N 0.000 description 2
- 108700018351 Major Histocompatibility Complex Proteins 0.000 description 2
- ZDZOTLJHXYCWBA-VCVYQWHSSA-N N-debenzoyl-N-(tert-butoxycarbonyl)-10-deacetyltaxol Chemical compound O([C@H]1[C@H]2[C@@](C([C@H](O)C3=C(C)[C@@H](OC(=O)[C@H](O)[C@@H](NC(=O)OC(C)(C)C)C=4C=CC=CC=4)C[C@]1(O)C3(C)C)=O)(C)[C@@H](O)C[C@H]1OC[C@]12OC(=O)C)C(=O)C1=CC=CC=C1 ZDZOTLJHXYCWBA-VCVYQWHSSA-N 0.000 description 2
- 206010060862 Prostate cancer Diseases 0.000 description 2
- 208000000236 Prostatic Neoplasms Diseases 0.000 description 2
- 206010039491 Sarcoma Diseases 0.000 description 2
- 206010040047 Sepsis Diseases 0.000 description 2
- 108020004459 Small interfering RNA Proteins 0.000 description 2
- 229930006000 Sucrose Natural products 0.000 description 2
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 2
- COQLPRJCUIATTQ-UHFFFAOYSA-N Uranyl acetate Chemical compound O.O.O=[U]=O.CC(O)=O.CC(O)=O COQLPRJCUIATTQ-UHFFFAOYSA-N 0.000 description 2
- 208000006105 Uterine Cervical Neoplasms Diseases 0.000 description 2
- 201000004810 Vascular dementia Diseases 0.000 description 2
- 206010047115 Vasculitis Diseases 0.000 description 2
- RJURFGZVJUQBHK-IIXSONLDSA-N actinomycin D Chemical compound C[C@H]1OC(=O)[C@H](C(C)C)N(C)C(=O)CN(C)C(=O)[C@@H]2CCCN2C(=O)[C@@H](C(C)C)NC(=O)[C@H]1NC(=O)C1=C(N)C(=O)C(C)=C2OC(C(C)=CC=C3C(=O)N[C@@H]4C(=O)N[C@@H](C(N5CCC[C@H]5C(=O)N(C)CC(=O)N(C)[C@@H](C(C)C)C(=O)O[C@@H]4C)=O)C(C)C)=C3N=C21 RJURFGZVJUQBHK-IIXSONLDSA-N 0.000 description 2
- 230000004913 activation Effects 0.000 description 2
- AWUCVROLDVIAJX-UHFFFAOYSA-N alpha-glycerophosphate Natural products OCC(O)COP(O)(O)=O AWUCVROLDVIAJX-UHFFFAOYSA-N 0.000 description 2
- 125000003277 amino group Chemical group 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 208000011775 arteriosclerosis disease Diseases 0.000 description 2
- 208000006673 asthma Diseases 0.000 description 2
- 230000003115 biocidal effect Effects 0.000 description 2
- 229960001561 bleomycin Drugs 0.000 description 2
- OYVAGSVQBOHSSS-UAPAGMARSA-O bleomycin A2 Chemical compound N([C@H](C(=O)N[C@H](C)[C@@H](O)[C@H](C)C(=O)N[C@@H]([C@H](O)C)C(=O)NCCC=1SC=C(N=1)C=1SC=C(N=1)C(=O)NCCC[S+](C)C)[C@@H](O[C@H]1[C@H]([C@@H](O)[C@H](O)[C@H](CO)O1)O[C@@H]1[C@H]([C@@H](OC(N)=O)[C@H](O)[C@@H](CO)O1)O)C=1N=CNC=1)C(=O)C1=NC([C@H](CC(N)=O)NC[C@H](N)C(N)=O)=NC(N)=C1C OYVAGSVQBOHSSS-UAPAGMARSA-O 0.000 description 2
- 230000037396 body weight Effects 0.000 description 2
- 239000001506 calcium phosphate Substances 0.000 description 2
- 229910000389 calcium phosphate Inorganic materials 0.000 description 2
- 235000011010 calcium phosphates Nutrition 0.000 description 2
- 229910052799 carbon Inorganic materials 0.000 description 2
- 239000002041 carbon nanotube Substances 0.000 description 2
- 229910021393 carbon nanotube Inorganic materials 0.000 description 2
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 2
- 238000004113 cell culture Methods 0.000 description 2
- 230000032823 cell division Effects 0.000 description 2
- 201000010881 cervical cancer Diseases 0.000 description 2
- DQLATGHUWYMOKM-UHFFFAOYSA-L cisplatin Chemical compound N[Pt](N)(Cl)Cl DQLATGHUWYMOKM-UHFFFAOYSA-L 0.000 description 2
- 229960004316 cisplatin Drugs 0.000 description 2
- 239000003184 complementary RNA Substances 0.000 description 2
- 229910052802 copper Inorganic materials 0.000 description 2
- 239000010949 copper Substances 0.000 description 2
- 230000001086 cytosolic effect Effects 0.000 description 2
- 229960000640 dactinomycin Drugs 0.000 description 2
- 229960000975 daunorubicin Drugs 0.000 description 2
- STQGQHZAVUOBTE-VGBVRHCVSA-N daunorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(C)=O)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 STQGQHZAVUOBTE-VGBVRHCVSA-N 0.000 description 2
- 230000018044 dehydration Effects 0.000 description 2
- 238000006297 dehydration reaction Methods 0.000 description 2
- 230000029087 digestion Effects 0.000 description 2
- 238000010790 dilution Methods 0.000 description 2
- 239000012895 dilution Substances 0.000 description 2
- 239000012153 distilled water Substances 0.000 description 2
- 229960003668 docetaxel Drugs 0.000 description 2
- 229940115080 doxil Drugs 0.000 description 2
- 238000001378 electrochemiluminescence detection Methods 0.000 description 2
- 230000003203 everyday effect Effects 0.000 description 2
- 230000005284 excitation Effects 0.000 description 2
- 230000001747 exhibiting effect Effects 0.000 description 2
- 235000019197 fats Nutrition 0.000 description 2
- MHMNJMPURVTYEJ-UHFFFAOYSA-N fluorescein-5-isothiocyanate Chemical compound O1C(=O)C2=CC(N=C=S)=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 MHMNJMPURVTYEJ-UHFFFAOYSA-N 0.000 description 2
- PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 description 2
- 239000010931 gold Substances 0.000 description 2
- 229910052737 gold Inorganic materials 0.000 description 2
- 208000035474 group of disease Diseases 0.000 description 2
- 239000001963 growth medium Substances 0.000 description 2
- 230000036541 health Effects 0.000 description 2
- 230000036571 hydration Effects 0.000 description 2
- 238000006703 hydration reaction Methods 0.000 description 2
- GRRNUXAQVGOGFE-NZSRVPFOSA-N hygromycin B Chemical compound O[C@@H]1[C@@H](NC)C[C@@H](N)[C@H](O)[C@H]1O[C@H]1[C@H]2O[C@@]3([C@@H]([C@@H](O)[C@@H](O)[C@@H](C(N)CO)O3)O)O[C@H]2[C@@H](O)[C@@H](CO)O1 GRRNUXAQVGOGFE-NZSRVPFOSA-N 0.000 description 2
- 229940097277 hygromycin b Drugs 0.000 description 2
- 238000012151 immunohistochemical method Methods 0.000 description 2
- CGIGDMFJXJATDK-UHFFFAOYSA-N indomethacin Chemical compound CC1=C(CC(O)=O)C2=CC(OC)=CC=C2N1C(=O)C1=CC=C(Cl)C=C1 CGIGDMFJXJATDK-UHFFFAOYSA-N 0.000 description 2
- 230000001939 inductive effect Effects 0.000 description 2
- 208000015181 infectious disease Diseases 0.000 description 2
- 230000002458 infectious effect Effects 0.000 description 2
- 230000002401 inhibitory effect Effects 0.000 description 2
- 238000011081 inoculation Methods 0.000 description 2
- 239000003446 ligand Substances 0.000 description 2
- 230000000670 limiting effect Effects 0.000 description 2
- 230000001404 mediated effect Effects 0.000 description 2
- 230000003287 optical effect Effects 0.000 description 2
- PHEDXBVPIONUQT-RGYGYFBISA-N phorbol 13-acetate 12-myristate Chemical compound C([C@]1(O)C(=O)C(C)=C[C@H]1[C@@]1(O)[C@H](C)[C@H]2OC(=O)CCCCCCCCCCCCC)C(CO)=C[C@H]1[C@H]1[C@]2(OC(C)=O)C1(C)C PHEDXBVPIONUQT-RGYGYFBISA-N 0.000 description 2
- 239000002244 precipitate Substances 0.000 description 2
- 238000001556 precipitation Methods 0.000 description 2
- 239000000941 radioactive substance Substances 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 238000003757 reverse transcription PCR Methods 0.000 description 2
- PYWVYCXTNDRMGF-UHFFFAOYSA-N rhodamine B Chemical compound [Cl-].C=12C=CC(=[N+](CC)CC)C=C2OC2=CC(N(CC)CC)=CC=C2C=1C1=CC=CC=C1C(O)=O PYWVYCXTNDRMGF-UHFFFAOYSA-N 0.000 description 2
- 230000011664 signaling Effects 0.000 description 2
- 239000002924 silencing RNA Substances 0.000 description 2
- 239000005720 sucrose Substances 0.000 description 2
- 230000020382 suppression by virus of host antigen processing and presentation of peptide antigen via MHC class I Effects 0.000 description 2
- 208000024891 symptom Diseases 0.000 description 2
- -1 that is Substances 0.000 description 2
- 230000008467 tissue growth Effects 0.000 description 2
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 2
- 102000003390 tumor necrosis factor Human genes 0.000 description 2
- 230000024883 vasodilation Effects 0.000 description 2
- 239000013598 vector Substances 0.000 description 2
- 229960004528 vincristine Drugs 0.000 description 2
- OGWKCGZFUXNPDA-XQKSVPLYSA-N vincristine Chemical compound C([N@]1C[C@@H](C[C@]2(C(=O)OC)C=3C(=CC4=C([C@]56[C@H]([C@@]([C@H](OC(C)=O)[C@]7(CC)C=CCN([C@H]67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)C[C@@](C1)(O)CC)CC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-XQKSVPLYSA-N 0.000 description 2
- OGWKCGZFUXNPDA-UHFFFAOYSA-N vincristine Natural products C1C(CC)(O)CC(CC2(C(=O)OC)C=3C(=CC4=C(C56C(C(C(OC(C)=O)C7(CC)C=CCN(C67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)CN1CCC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-UHFFFAOYSA-N 0.000 description 2
- MWWSFMDVAYGXBV-MYPASOLCSA-N (7r,9s)-7-[(2r,4s,5s,6s)-4-amino-5-hydroxy-6-methyloxan-2-yl]oxy-6,9,11-trihydroxy-9-(2-hydroxyacetyl)-4-methoxy-8,10-dihydro-7h-tetracene-5,12-dione;hydrochloride Chemical compound Cl.O([C@@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 MWWSFMDVAYGXBV-MYPASOLCSA-N 0.000 description 1
- IAKPHLATFBHGOB-UHFFFAOYSA-M 1,1'-dioctadecyl-3,3,3'3'-tetramethylindocarbocyanine perchlorate Chemical compound [O-]Cl(=O)(=O)=O.CC1(C)C2=CC=CC=C2N(CCCCCCCCCCCCCCCCC)\C1=C/C=C/C1=[N+](CCCCCCCCCCCCCCCCC)C2=CC=CC=C2C1(C)C IAKPHLATFBHGOB-UHFFFAOYSA-M 0.000 description 1
- QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 1
- DJQYYYCQOZMCRC-UHFFFAOYSA-N 2-aminopropane-1,3-dithiol Chemical group SCC(N)CS DJQYYYCQOZMCRC-UHFFFAOYSA-N 0.000 description 1
- FWBHETKCLVMNFS-UHFFFAOYSA-N 4',6-Diamino-2-phenylindol Chemical compound C1=CC(C(=N)N)=CC=C1C1=CC2=CC=C(C(N)=N)C=C2N1 FWBHETKCLVMNFS-UHFFFAOYSA-N 0.000 description 1
- AOJJSUZBOXZQNB-VTZDEGQISA-N 4'-epidoxorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@@H](O)[C@H](C)O1 AOJJSUZBOXZQNB-VTZDEGQISA-N 0.000 description 1
- VIBDVOOELVZGDU-UHFFFAOYSA-N 4-(1h-indol-2-yl)benzene-1,3-dicarboximidamide Chemical compound NC(=N)C1=CC(C(=N)N)=CC=C1C1=CC2=CC=CC=C2N1 VIBDVOOELVZGDU-UHFFFAOYSA-N 0.000 description 1
- 208000024827 Alzheimer disease Diseases 0.000 description 1
- 206010002091 Anaesthesia Diseases 0.000 description 1
- 208000003343 Antiphospholipid Syndrome Diseases 0.000 description 1
- 108091023037 Aptamer Proteins 0.000 description 1
- 201000001320 Atherosclerosis Diseases 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- 208000009137 Behcet syndrome Diseases 0.000 description 1
- 206010005949 Bone cancer Diseases 0.000 description 1
- 208000018084 Bone neoplasm Diseases 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 208000014644 Brain disease Diseases 0.000 description 1
- 241000219198 Brassica Species 0.000 description 1
- 235000003351 Brassica cretica Nutrition 0.000 description 1
- 235000003343 Brassica rupestris Nutrition 0.000 description 1
- 206010006448 Bronchiolitis Diseases 0.000 description 1
- COVZYZSDYWQREU-UHFFFAOYSA-N Busulfan Chemical compound CS(=O)(=O)OCCCCOS(C)(=O)=O COVZYZSDYWQREU-UHFFFAOYSA-N 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- 206010048610 Cardiotoxicity Diseases 0.000 description 1
- 102000016289 Cell Adhesion Molecules Human genes 0.000 description 1
- 108010067225 Cell Adhesion Molecules Proteins 0.000 description 1
- 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 description 1
- 108020004635 Complementary DNA Proteins 0.000 description 1
- CMSMOCZEIVJLDB-UHFFFAOYSA-N Cyclophosphamide Chemical compound ClCCN(CCCl)P1(=O)NCCCO1 CMSMOCZEIVJLDB-UHFFFAOYSA-N 0.000 description 1
- 239000012624 DNA alkylating agent Substances 0.000 description 1
- 230000004543 DNA replication Effects 0.000 description 1
- 108010053770 Deoxyribonucleases Proteins 0.000 description 1
- 102000016911 Deoxyribonucleases Human genes 0.000 description 1
- 206010012438 Dermatitis atopic Diseases 0.000 description 1
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 1
- 238000002965 ELISA Methods 0.000 description 1
- 208000005189 Embolism Diseases 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- 206010014561 Emphysema Diseases 0.000 description 1
- 201000009273 Endometriosis Diseases 0.000 description 1
- HTIJFSOGRVMCQR-UHFFFAOYSA-N Epirubicin Natural products COc1cccc2C(=O)c3c(O)c4CC(O)(CC(OC5CC(N)C(=O)C(C)O5)c4c(O)c3C(=O)c12)C(=O)CO HTIJFSOGRVMCQR-UHFFFAOYSA-N 0.000 description 1
- 241000283086 Equidae Species 0.000 description 1
- 108090000371 Esterases Proteins 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- 229920001917 Ficoll Polymers 0.000 description 1
- WJOHZNCJWYWUJD-IUGZLZTKSA-N Fluocinonide Chemical compound C1([C@@H](F)C2)=CC(=O)C=C[C@]1(C)[C@]1(F)[C@@H]2[C@@H]2C[C@H]3OC(C)(C)O[C@@]3(C(=O)COC(=O)C)[C@@]2(C)C[C@@H]1O WJOHZNCJWYWUJD-IUGZLZTKSA-N 0.000 description 1
- 238000012413 Fluorescence activated cell sorting analysis Methods 0.000 description 1
- 101150066002 GFP gene Proteins 0.000 description 1
- 208000022072 Gallbladder Neoplasms Diseases 0.000 description 1
- 208000007882 Gastritis Diseases 0.000 description 1
- 208000017189 Gastrointestinal inflammatory disease Diseases 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Chemical compound OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 201000005569 Gout Diseases 0.000 description 1
- 102000004144 Green Fluorescent Proteins Human genes 0.000 description 1
- 206010020565 Hyperaemia Diseases 0.000 description 1
- HEFNNWSXXWATRW-UHFFFAOYSA-N Ibuprofen Chemical compound CC(C)CC1=CC=C(C(C)C(O)=O)C=C1 HEFNNWSXXWATRW-UHFFFAOYSA-N 0.000 description 1
- XDXDZDZNSLXDNA-TZNDIEGXSA-N Idarubicin Chemical compound C1[C@H](N)[C@H](O)[C@H](C)O[C@H]1O[C@@H]1C2=C(O)C(C(=O)C3=CC=CC=C3C3=O)=C3C(O)=C2C[C@@](O)(C(C)=O)C1 XDXDZDZNSLXDNA-TZNDIEGXSA-N 0.000 description 1
- XDXDZDZNSLXDNA-UHFFFAOYSA-N Idarubicin Natural products C1C(N)C(O)C(C)OC1OC1C2=C(O)C(C(=O)C3=CC=CC=C3C3=O)=C3C(O)=C2CC(O)(C(C)=O)C1 XDXDZDZNSLXDNA-UHFFFAOYSA-N 0.000 description 1
- 208000022559 Inflammatory bowel disease Diseases 0.000 description 1
- YQEZLKZALYSWHR-UHFFFAOYSA-N Ketamine Chemical compound C=1C=CC=C(Cl)C=1C1(NC)CCCCC1=O YQEZLKZALYSWHR-UHFFFAOYSA-N 0.000 description 1
- 208000008839 Kidney Neoplasms Diseases 0.000 description 1
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 description 1
- 206010023825 Laryngeal cancer Diseases 0.000 description 1
- 201000008197 Laryngitis Diseases 0.000 description 1
- 102000003960 Ligases Human genes 0.000 description 1
- 108090000364 Ligases Proteins 0.000 description 1
- 206010025323 Lymphomas Diseases 0.000 description 1
- 108010030317 Macrophage-1 Antigen Proteins 0.000 description 1
- 239000005913 Maltodextrin Substances 0.000 description 1
- 229920002774 Maltodextrin Polymers 0.000 description 1
- 102000018897 Membrane Fusion Proteins Human genes 0.000 description 1
- 108010027796 Membrane Fusion Proteins Proteins 0.000 description 1
- 229930192392 Mitomycin Natural products 0.000 description 1
- 208000034578 Multiple myelomas Diseases 0.000 description 1
- 241000699660 Mus musculus Species 0.000 description 1
- 208000002231 Muscle Neoplasms Diseases 0.000 description 1
- 208000021642 Muscular disease Diseases 0.000 description 1
- 208000009525 Myocarditis Diseases 0.000 description 1
- 201000009623 Myopathy Diseases 0.000 description 1
- NWIBSHFKIJFRCO-WUDYKRTCSA-N Mytomycin Chemical compound C1N2C(C(C(C)=C(N)C3=O)=O)=C3[C@@H](COC(N)=O)[C@@]2(OC)[C@@H]2[C@H]1N2 NWIBSHFKIJFRCO-WUDYKRTCSA-N 0.000 description 1
- 206010030113 Oedema Diseases 0.000 description 1
- 206010030216 Oesophagitis Diseases 0.000 description 1
- 206010033078 Otitis media Diseases 0.000 description 1
- 239000002033 PVDF binder Substances 0.000 description 1
- 206010033645 Pancreatitis Diseases 0.000 description 1
- 208000008469 Peptic Ulcer Diseases 0.000 description 1
- 102000003992 Peroxidases Human genes 0.000 description 1
- 206010035226 Plasma cell myeloma Diseases 0.000 description 1
- 206010035664 Pneumonia Diseases 0.000 description 1
- 201000004681 Psoriasis Diseases 0.000 description 1
- 206010037660 Pyrexia Diseases 0.000 description 1
- 238000012228 RNA interference-mediated gene silencing Methods 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- 208000015634 Rectal Neoplasms Diseases 0.000 description 1
- 206010038389 Renal cancer Diseases 0.000 description 1
- 208000021386 Sjogren Syndrome Diseases 0.000 description 1
- 208000000453 Skin Neoplasms Diseases 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 208000006045 Spondylarthropathies Diseases 0.000 description 1
- 208000005718 Stomach Neoplasms Diseases 0.000 description 1
- ZSJLQEPLLKMAKR-UHFFFAOYSA-N Streptozotocin Natural products O=NN(C)C(=O)NC1C(O)OC(CO)C(O)C1O ZSJLQEPLLKMAKR-UHFFFAOYSA-N 0.000 description 1
- 208000006011 Stroke Diseases 0.000 description 1
- 201000009594 Systemic Scleroderma Diseases 0.000 description 1
- 206010042953 Systemic sclerosis Diseases 0.000 description 1
- FOCVUCIESVLUNU-UHFFFAOYSA-N Thiotepa Chemical compound C1CN1P(N1CC1)(=S)N1CC1 FOCVUCIESVLUNU-UHFFFAOYSA-N 0.000 description 1
- 108090000190 Thrombin Proteins 0.000 description 1
- 208000007536 Thrombosis Diseases 0.000 description 1
- 206010046914 Vaginal infection Diseases 0.000 description 1
- 201000008100 Vaginitis Diseases 0.000 description 1
- JXLYSJRDGCGARV-WWYNWVTFSA-N Vinblastine Natural products O=C(O[C@H]1[C@](O)(C(=O)OC)[C@@H]2N(C)c3c(cc(c(OC)c3)[C@]3(C(=O)OC)c4[nH]c5c(c4CCN4C[C@](O)(CC)C[C@H](C3)C4)cccc5)[C@@]32[C@H]2[C@@]1(CC)C=CCN2CC3)C JXLYSJRDGCGARV-WWYNWVTFSA-N 0.000 description 1
- 241000700605 Viruses Species 0.000 description 1
- 210000000683 abdominal cavity Anatomy 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 208000038016 acute inflammation Diseases 0.000 description 1
- 230000006022 acute inflammation Effects 0.000 description 1
- 206010000891 acute myocardial infarction Diseases 0.000 description 1
- 206010001053 acute respiratory failure Diseases 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- TTWYZDPBDWHJOR-IDIVVRGQSA-L adenosine triphosphate disodium Chemical compound [Na+].[Na+].C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](COP(O)(=O)OP(O)(=O)OP([O-])([O-])=O)[C@@H](O)[C@H]1O TTWYZDPBDWHJOR-IDIVVRGQSA-L 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 238000000246 agarose gel electrophoresis Methods 0.000 description 1
- 229930013930 alkaloid Natural products 0.000 description 1
- 150000003797 alkaloid derivatives Chemical class 0.000 description 1
- 230000000172 allergic effect Effects 0.000 description 1
- 229960003099 amcinonide Drugs 0.000 description 1
- ILKJAFIWWBXGDU-MOGDOJJUSA-N amcinonide Chemical compound O([C@@]1([C@H](O2)C[C@@H]3[C@@]1(C[C@H](O)[C@]1(F)[C@@]4(C)C=CC(=O)C=C4CC[C@H]13)C)C(=O)COC(=O)C)C12CCCC1 ILKJAFIWWBXGDU-MOGDOJJUSA-N 0.000 description 1
- 230000037005 anaesthesia Effects 0.000 description 1
- 230000033115 angiogenesis Effects 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 230000005875 antibody response Effects 0.000 description 1
- 238000011394 anticancer treatment Methods 0.000 description 1
- 230000010100 anticoagulation Effects 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- YZXBAPSDXZZRGB-DOFZRALJSA-N arachidonic acid Chemical class CCCCC\C=C/C\C=C/C\C=C/C\C=C/CCCC(O)=O YZXBAPSDXZZRGB-DOFZRALJSA-N 0.000 description 1
- 201000008937 atopic dermatitis Diseases 0.000 description 1
- 208000010668 atopic eczema Diseases 0.000 description 1
- 230000001363 autoimmune Effects 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 238000010170 biological method Methods 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- QKSKPIVNLNLAAV-UHFFFAOYSA-N bis(2-chloroethyl) sulfide Chemical compound ClCCSCCCl QKSKPIVNLNLAAV-UHFFFAOYSA-N 0.000 description 1
- 238000004820 blood count Methods 0.000 description 1
- 210000001124 body fluid Anatomy 0.000 description 1
- 239000010839 body fluid Substances 0.000 description 1
- UDSAIICHUKSCKT-UHFFFAOYSA-N bromophenol blue Chemical compound C1=C(Br)C(O)=C(Br)C=C1C1(C=2C=C(Br)C(O)=C(Br)C=2)C2=CC=CC=C2S(=O)(=O)O1 UDSAIICHUKSCKT-UHFFFAOYSA-N 0.000 description 1
- 201000009267 bronchiectasis Diseases 0.000 description 1
- 206010006451 bronchitis Diseases 0.000 description 1
- 239000007975 buffered saline Substances 0.000 description 1
- 229960002092 busulfan Drugs 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 231100000259 cardiotoxicity Toxicity 0.000 description 1
- 229960005243 carmustine Drugs 0.000 description 1
- 239000002771 cell marker Substances 0.000 description 1
- 230000010307 cell transformation Effects 0.000 description 1
- 230000019522 cellular metabolic process Effects 0.000 description 1
- 230000007541 cellular toxicity Effects 0.000 description 1
- 239000000919 ceramic Substances 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- JCKYGMPEJWAADB-UHFFFAOYSA-N chlorambucil Chemical compound OC(=O)CCCC1=CC=C(N(CCCl)CCCl)C=C1 JCKYGMPEJWAADB-UHFFFAOYSA-N 0.000 description 1
- 229960004630 chlorambucil Drugs 0.000 description 1
- 208000003167 cholangitis Diseases 0.000 description 1
- 201000001352 cholecystitis Diseases 0.000 description 1
- 208000037976 chronic inflammation Diseases 0.000 description 1
- 230000006020 chronic inflammation Effects 0.000 description 1
- 229960004703 clobetasol propionate Drugs 0.000 description 1
- CBGUOGMQLZIXBE-XGQKBEPLSA-N clobetasol propionate Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@H](C)[C@@](C(=O)CCl)(OC(=O)CC)[C@@]1(C)C[C@@H]2O CBGUOGMQLZIXBE-XGQKBEPLSA-N 0.000 description 1
- 210000001072 colon Anatomy 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 238000002648 combination therapy Methods 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 210000001608 connective tissue cell Anatomy 0.000 description 1
- 239000000470 constituent Substances 0.000 description 1
- 230000030944 contact inhibition Effects 0.000 description 1
- 239000002872 contrast media Substances 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 229960004397 cyclophosphamide Drugs 0.000 description 1
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 1
- 235000018417 cysteine Nutrition 0.000 description 1
- 210000000805 cytoplasm Anatomy 0.000 description 1
- 210000000172 cytosol Anatomy 0.000 description 1
- 230000003412 degenerative effect Effects 0.000 description 1
- 230000000593 degrading effect Effects 0.000 description 1
- 230000001934 delay Effects 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 229960002593 desoximetasone Drugs 0.000 description 1
- VWVSBHGCDBMOOT-IIEHVVJPSA-N desoximetasone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@@H](C)[C@H](C(=O)CO)[C@@]1(C)C[C@@H]2O VWVSBHGCDBMOOT-IIEHVVJPSA-N 0.000 description 1
- 239000003599 detergent Substances 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- 229960001259 diclofenac Drugs 0.000 description 1
- DCOPUUMXTXDBNB-UHFFFAOYSA-N diclofenac Chemical compound OC(=O)CC1=CC=CC=C1NC1=C(Cl)C=CC=C1Cl DCOPUUMXTXDBNB-UHFFFAOYSA-N 0.000 description 1
- 235000005911 diet Nutrition 0.000 description 1
- 230000037213 diet Effects 0.000 description 1
- 229960002124 diflorasone diacetate Drugs 0.000 description 1
- BOBLHFUVNSFZPJ-JOYXJVLSSA-N diflorasone diacetate Chemical compound C1([C@@H](F)C2)=CC(=O)C=C[C@]1(C)[C@]1(F)[C@@H]2[C@@H]2C[C@H](C)[C@@](C(=O)COC(C)=O)(OC(C)=O)[C@@]2(C)C[C@@H]1O BOBLHFUVNSFZPJ-JOYXJVLSSA-N 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 239000002270 dispersing agent Substances 0.000 description 1
- 208000009190 disseminated intravascular coagulation Diseases 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 230000000235 effect on cancer Effects 0.000 description 1
- 230000002526 effect on cardiovascular system Effects 0.000 description 1
- 238000001962 electrophoresis Methods 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 206010014665 endocarditis Diseases 0.000 description 1
- 230000002124 endocrine Effects 0.000 description 1
- 210000002889 endothelial cell Anatomy 0.000 description 1
- 229940030275 epigallocatechin gallate Drugs 0.000 description 1
- 229960001904 epirubicin Drugs 0.000 description 1
- 210000002919 epithelial cell Anatomy 0.000 description 1
- 208000006881 esophagitis Diseases 0.000 description 1
- VJJPUSNTGOMMGY-MRVIYFEKSA-N etoposide Chemical compound COC1=C(O)C(OC)=CC([C@@H]2C3=CC=4OCOC=4C=C3[C@@H](O[C@H]3[C@@H]([C@@H](O)[C@@H]4O[C@H](C)OC[C@H]4O3)O)[C@@H]3[C@@H]2C(OC3)=O)=C1 VJJPUSNTGOMMGY-MRVIYFEKSA-N 0.000 description 1
- 229960005420 etoposide Drugs 0.000 description 1
- 230000029142 excretion Effects 0.000 description 1
- 239000000835 fiber Substances 0.000 description 1
- 229960000785 fluocinonide Drugs 0.000 description 1
- 238000002073 fluorescence micrograph Methods 0.000 description 1
- 238000001997 free-flow electrophoresis Methods 0.000 description 1
- 201000010175 gallbladder cancer Diseases 0.000 description 1
- 206010017758 gastric cancer Diseases 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 238000002523 gelfiltration Methods 0.000 description 1
- 230000009368 gene silencing by RNA Effects 0.000 description 1
- 238000001415 gene therapy Methods 0.000 description 1
- 239000003193 general anesthetic agent Substances 0.000 description 1
- 208000005017 glioblastoma Diseases 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 201000005787 hematologic cancer Diseases 0.000 description 1
- 208000024200 hematopoietic and lymphoid system neoplasm Diseases 0.000 description 1
- 210000003958 hematopoietic stem cell Anatomy 0.000 description 1
- 208000006454 hepatitis Diseases 0.000 description 1
- 231100000283 hepatitis Toxicity 0.000 description 1
- 229940022353 herceptin Drugs 0.000 description 1
- 229960001680 ibuprofen Drugs 0.000 description 1
- 229960000908 idarubicin Drugs 0.000 description 1
- HOMGKSMUEGBAAB-UHFFFAOYSA-N ifosfamide Chemical compound ClCCNP1(=O)OCCCN1CCCl HOMGKSMUEGBAAB-UHFFFAOYSA-N 0.000 description 1
- 229960001101 ifosfamide Drugs 0.000 description 1
- 238000003384 imaging method Methods 0.000 description 1
- 238000007654 immersion Methods 0.000 description 1
- 210000000987 immune system Anatomy 0.000 description 1
- 230000036039 immunity Effects 0.000 description 1
- 239000003018 immunosuppressive agent Substances 0.000 description 1
- 229940125721 immunosuppressive agent Drugs 0.000 description 1
- 230000001976 improved effect Effects 0.000 description 1
- 229960000905 indomethacin Drugs 0.000 description 1
- 230000028709 inflammatory response Effects 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 108010044426 integrins Proteins 0.000 description 1
- 102000006495 integrins Human genes 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 201000006334 interstitial nephritis Diseases 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 230000031146 intracellular signal transduction Effects 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- NBQNWMBBSKPBAY-UHFFFAOYSA-N iodixanol Chemical compound IC=1C(C(=O)NCC(O)CO)=C(I)C(C(=O)NCC(O)CO)=C(I)C=1N(C(=O)C)CC(O)CN(C(C)=O)C1=C(I)C(C(=O)NCC(O)CO)=C(I)C(C(=O)NCC(O)CO)=C1I NBQNWMBBSKPBAY-UHFFFAOYSA-N 0.000 description 1
- 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 1
- SZVJSHCCFOBDDC-UHFFFAOYSA-N iron(II,III) oxide Inorganic materials O=[Fe]O[Fe]O[Fe]=O SZVJSHCCFOBDDC-UHFFFAOYSA-N 0.000 description 1
- 230000000302 ischemic effect Effects 0.000 description 1
- 229960003299 ketamine Drugs 0.000 description 1
- 201000010982 kidney cancer Diseases 0.000 description 1
- 208000017169 kidney disease Diseases 0.000 description 1
- 206010023841 laryngeal neoplasm Diseases 0.000 description 1
- 208000032839 leukemia Diseases 0.000 description 1
- 201000007270 liver cancer Diseases 0.000 description 1
- 208000014018 liver neoplasm Diseases 0.000 description 1
- 229960002247 lomustine Drugs 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 239000012139 lysis buffer Substances 0.000 description 1
- 239000006249 magnetic particle Substances 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 229940035034 maltodextrin Drugs 0.000 description 1
- 108010082117 matrigel Proteins 0.000 description 1
- 238000010297 mechanical methods and process Methods 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- HAWPXGHAZFHHAD-UHFFFAOYSA-N mechlorethamine Chemical compound ClCCN(C)CCCl HAWPXGHAZFHHAD-UHFFFAOYSA-N 0.000 description 1
- 229960004961 mechlorethamine Drugs 0.000 description 1
- 108020004999 messenger RNA Proteins 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 229910021645 metal ion Inorganic materials 0.000 description 1
- 239000002923 metal particle Substances 0.000 description 1
- 244000005700 microbiome Species 0.000 description 1
- 238000001000 micrograph Methods 0.000 description 1
- 238000000520 microinjection Methods 0.000 description 1
- CFCUWKMKBJTWLW-BKHRDMLASA-N mithramycin Chemical compound O([C@@H]1C[C@@H](O[C@H](C)[C@H]1O)OC=1C=C2C=C3C[C@H]([C@@H](C(=O)C3=C(O)C2=C(O)C=1C)O[C@@H]1O[C@H](C)[C@@H](O)[C@H](O[C@@H]2O[C@H](C)[C@H](O)[C@H](O[C@@H]3O[C@H](C)[C@@H](O)[C@@](C)(O)C3)C2)C1)[C@H](OC)C(=O)[C@@H](O)[C@@H](C)O)[C@H]1C[C@@H](O)[C@H](O)[C@@H](C)O1 CFCUWKMKBJTWLW-BKHRDMLASA-N 0.000 description 1
- 229960004857 mitomycin Drugs 0.000 description 1
- KKZJGLLVHKMTCM-UHFFFAOYSA-N mitoxantrone Chemical compound O=C1C2=C(O)C=CC(O)=C2C(=O)C2=C1C(NCCNCCO)=CC=C2NCCNCCO KKZJGLLVHKMTCM-UHFFFAOYSA-N 0.000 description 1
- 229960001156 mitoxantrone Drugs 0.000 description 1
- 239000011259 mixed solution Substances 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 229960002744 mometasone furoate Drugs 0.000 description 1
- WOFMFGQZHJDGCX-ZULDAHANSA-N mometasone furoate Chemical compound O([C@]1([C@@]2(C)C[C@H](O)[C@]3(Cl)[C@@]4(C)C=CC(=O)C=C4CC[C@H]3[C@@H]2C[C@H]1C)C(=O)CCl)C(=O)C1=CC=CO1 WOFMFGQZHJDGCX-ZULDAHANSA-N 0.000 description 1
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 description 1
- 210000003205 muscle Anatomy 0.000 description 1
- 201000002077 muscle cancer Diseases 0.000 description 1
- 210000002346 musculoskeletal system Anatomy 0.000 description 1
- 235000010460 mustard Nutrition 0.000 description 1
- 229940031182 nanoparticles iron oxide Drugs 0.000 description 1
- 201000009240 nasopharyngitis Diseases 0.000 description 1
- 210000000944 nerve tissue Anatomy 0.000 description 1
- 208000002154 non-small cell lung carcinoma Diseases 0.000 description 1
- 230000009871 nonspecific binding Effects 0.000 description 1
- 238000011580 nude mouse model Methods 0.000 description 1
- 230000003204 osmotic effect Effects 0.000 description 1
- 201000008482 osteoarthritis Diseases 0.000 description 1
- 230000007310 pathophysiology Effects 0.000 description 1
- 208000011906 peptic ulcer disease Diseases 0.000 description 1
- 208000008494 pericarditis Diseases 0.000 description 1
- 230000035699 permeability Effects 0.000 description 1
- 108040007629 peroxidase activity proteins Proteins 0.000 description 1
- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 description 1
- 229960005190 phenylalanine Drugs 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 229960002702 piroxicam Drugs 0.000 description 1
- QYSPLQLAKJAUJT-UHFFFAOYSA-N piroxicam Chemical compound OC=1C2=CC=CC=C2S(=O)(=O)N(C)C=1C(=O)NC1=CC=CC=N1 QYSPLQLAKJAUJT-UHFFFAOYSA-N 0.000 description 1
- 229920003023 plastic Polymers 0.000 description 1
- 239000004033 plastic Substances 0.000 description 1
- 229960003171 plicamycin Drugs 0.000 description 1
- 229920002401 polyacrylamide Polymers 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 229960004618 prednisone Drugs 0.000 description 1
- XOFYZVNMUHMLCC-ZPOLXVRWSA-N prednisone Chemical compound O=C1C=C[C@]2(C)[C@H]3C(=O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 XOFYZVNMUHMLCC-ZPOLXVRWSA-N 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 230000004853 protein function Effects 0.000 description 1
- 210000001938 protoplast Anatomy 0.000 description 1
- 208000020016 psychiatric disease Diseases 0.000 description 1
- 208000005069 pulmonary fibrosis Diseases 0.000 description 1
- 239000002510 pyrogen Substances 0.000 description 1
- 238000001959 radiotherapy Methods 0.000 description 1
- 102000005962 receptors Human genes 0.000 description 1
- 108020003175 receptors Proteins 0.000 description 1
- 206010038038 rectal cancer Diseases 0.000 description 1
- 201000001275 rectum cancer Diseases 0.000 description 1
- 108010054624 red fluorescent protein Proteins 0.000 description 1
- 201000004193 respiratory failure Diseases 0.000 description 1
- 108091008146 restriction endonucleases Proteins 0.000 description 1
- 206010039073 rheumatoid arthritis Diseases 0.000 description 1
- 206010039083 rhinitis Diseases 0.000 description 1
- 229960004641 rituximab Drugs 0.000 description 1
- 201000000980 schizophrenia Diseases 0.000 description 1
- 238000006748 scratching Methods 0.000 description 1
- 230000002393 scratching effect Effects 0.000 description 1
- 238000009097 single-agent therapy Methods 0.000 description 1
- 201000009890 sinusitis Diseases 0.000 description 1
- 235000020183 skimmed milk Nutrition 0.000 description 1
- 201000000849 skin cancer Diseases 0.000 description 1
- 150000003384 small molecules Chemical class 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 1
- 230000009870 specific binding Effects 0.000 description 1
- 201000005671 spondyloarthropathy Diseases 0.000 description 1
- 239000008223 sterile water Substances 0.000 description 1
- 230000004936 stimulating effect Effects 0.000 description 1
- 201000011549 stomach cancer Diseases 0.000 description 1
- 229960001052 streptozocin Drugs 0.000 description 1
- ZSJLQEPLLKMAKR-GKHCUFPYSA-N streptozocin Chemical compound O=NN(C)C(=O)N[C@H]1[C@@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O ZSJLQEPLLKMAKR-GKHCUFPYSA-N 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 201000000596 systemic lupus erythematosus Diseases 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- NRUKOCRGYNPUPR-QBPJDGROSA-N teniposide Chemical compound COC1=C(O)C(OC)=CC([C@@H]2C3=CC=4OCOC=4C=C3[C@@H](O[C@H]3[C@@H]([C@@H](O)[C@@H]4O[C@@H](OC[C@H]4O3)C=3SC=CC=3)O)[C@@H]3[C@@H]2C(OC3)=O)=C1 NRUKOCRGYNPUPR-QBPJDGROSA-N 0.000 description 1
- 229960001278 teniposide Drugs 0.000 description 1
- 238000010257 thawing Methods 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 125000003396 thiol group Chemical group [H]S* 0.000 description 1
- 229960001196 thiotepa Drugs 0.000 description 1
- 229960004072 thrombin Drugs 0.000 description 1
- 206010043778 thyroiditis Diseases 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 229960000303 topotecan Drugs 0.000 description 1
- UCFGDBYHRUNTLO-QHCPKHFHSA-N topotecan Chemical compound C1=C(O)C(CN(C)C)=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)[C@]5(O)CC)C4=NC2=C1 UCFGDBYHRUNTLO-QHCPKHFHSA-N 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 238000013518 transcription Methods 0.000 description 1
- 230000035897 transcription Effects 0.000 description 1
- 239000012096 transfection reagent Substances 0.000 description 1
- 238000013519 translation Methods 0.000 description 1
- 230000014616 translation Effects 0.000 description 1
- 230000000472 traumatic effect Effects 0.000 description 1
- 230000001960 triggered effect Effects 0.000 description 1
- 208000029729 tumor suppressor gene on chromosome 11 Diseases 0.000 description 1
- 229950008396 ulobetasol propionate Drugs 0.000 description 1
- BDSYKGHYMJNPAB-LICBFIPMSA-N ulobetasol propionate Chemical compound C1([C@@H](F)C2)=CC(=O)C=C[C@]1(C)[C@]1(F)[C@@H]2[C@@H]2C[C@H](C)[C@@](C(=O)CCl)(OC(=O)CC)[C@@]2(C)C[C@@H]1O BDSYKGHYMJNPAB-LICBFIPMSA-N 0.000 description 1
- 238000000108 ultra-filtration Methods 0.000 description 1
- 238000002604 ultrasonography Methods 0.000 description 1
- 210000003954 umbilical cord Anatomy 0.000 description 1
- 210000003606 umbilical vein Anatomy 0.000 description 1
- 231100000925 very toxic Toxicity 0.000 description 1
- 229960003048 vinblastine Drugs 0.000 description 1
- JXLYSJRDGCGARV-XQKSVPLYSA-N vincaleukoblastine Chemical compound C([C@@H](C[C@]1(C(=O)OC)C=2C(=CC3=C([C@]45[C@H]([C@@]([C@H](OC(C)=O)[C@]6(CC)C=CCN([C@H]56)CC4)(O)C(=O)OC)N3C)C=2)OC)C[C@@](C2)(O)CC)N2CCC2=C1NC1=CC=CC=C21 JXLYSJRDGCGARV-XQKSVPLYSA-N 0.000 description 1
- 238000001262 western blot Methods 0.000 description 1
- 239000012130 whole-cell lysate Substances 0.000 description 1
Images
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/10—Dispersions; Emulsions
- A61K9/127—Liposomes
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
- A61K9/5005—Wall or coating material
- A61K9/5063—Compounds of unknown constitution, e.g. material from plants or animals
- A61K9/5068—Cell membranes or bacterial membranes enclosing drugs
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
- A61K35/12—Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells
- A61K35/14—Blood; Artificial blood
- A61K35/15—Cells of the myeloid line, e.g. granulocytes, basophils, eosinophils, neutrophils, leucocytes, monocytes, macrophages or mast cells; Myeloid precursor cells; Antigen-presenting cells, e.g. dendritic cells
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
- A61K35/12—Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells
- A61K35/48—Reproductive organs
- A61K35/54—Ovaries; Ova; Ovules; Embryos; Foetal cells; Germ cells
- A61K35/545—Embryonic stem cells; Pluripotent stem cells; Induced pluripotent stem cells; Uncharacterised stem cells
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/10—Dispersions; Emulsions
- A61K9/127—Liposomes
- A61K9/1277—Processes for preparing; Proliposomes
- A61K9/1278—Post-loading, e.g. by ion or pH gradient
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Epidemiology (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
- Cell Biology (AREA)
- Engineering & Computer Science (AREA)
- Developmental Biology & Embryology (AREA)
- Zoology (AREA)
- Immunology (AREA)
- Virology (AREA)
- Reproductive Health (AREA)
- Hematology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biomedical Technology (AREA)
- Biotechnology (AREA)
- Dispersion Chemistry (AREA)
- Botany (AREA)
- Molecular Biology (AREA)
- Gynecology & Obstetrics (AREA)
- Biophysics (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicinal Preparation (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Manufacturing Of Micro-Capsules (AREA)
Description
本発明では、特定の組織へ誘導される細胞に由来するマイクロベシクル又はシェディングマイクロベシクルを使用し、或いは標的タンパク質を発現した形質転換細胞に由来するマイクロベシクル又はシェディングマイクロベシクルを使用することができる。これに加えて、前記細胞と形質転換細胞に細胞膜融合物質が発現するように形質転換された細胞に由来するマイクロベシクル又はシェディングマイクロベシクルを使用することができる。
本発明において、「マイクロベシクル」は、哺乳類の有核細胞から人為的に製造されたベシクルであって、由来する細胞の細胞膜成分からなる脂質二重膜によって内部と外部が区分され、細胞の細胞膜脂質及び細胞膜タンパク質、核酸、並びに細胞成分を持っており、元来細胞より大きさが小さいことを意味するが、これに限定されるものではない。本発明において、シェディングマイクロベシクルとは、細胞が自然的に分泌するベシクルであって、由来する細胞の細胞膜成分からなる脂質二重膜によって内部と外部が区分され、細胞の細胞脂質及び細胞膜タンパク質、核酸、並びに細胞成分を持っている元来細胞より大きさが小さいことをいう。
本発明では、細胞又は形質転換された哺乳類の有核細胞が発現している物質を使用し、必要に応じて、前記哺乳類の有核細胞に由来せず且つ細胞の外部で用意された物質を使用することができるが、これらに限定されるものではない。
図1は哺乳類の有核細胞又は形質転換された哺乳類の有核細胞からマイクロベシクルと標的誘導物質、治療用物質、診断用物質などの多様な物質が負荷されたマイクロベシクルを製造する方法を図式的に示す。
図1に示した模式図によって単核球又はマクロファージからマイクロベシクルを製造した。図1において超音波分解と密度勾配の方法を使用した。
実施例1の方法によって単核球で製造したマイクロベシクルをグロー放電炭素コート銅グリッド(glow-discharged carbon-coated copper grid)で3分間吸着させた。前記グリッドを蒸留水で洗浄した後、2%酢酸ウラニル(uranylacetate)で1分間染色(staining)した。JEM101(Jeol, Japan)電子顕微鏡で観察した結果を図2に示す。
実施例1の方法によって単核球から製造したマイクロベシクルを用意した。1μMの濃度でシクロデキストリンを仕込み、室温で1時間保管した。サンプルを5μg/mLの濃度でPBS1mLに希釈した。マイクロベシクル入りのPBS1mLをキュベットに入れて動的光散乱粒度分析器で分析し、その結果を図5に示す。
実施例1の方法によって単核球から製造したマイクロベシクルを用意した。1μMの濃度でコレステロール−ポリエチレングリコールを入れ、室温で1時間保管した。サンプルを5μg/mLの濃度でPBS1mLに希釈した。マイクロベシクル入りのPBS1mLをキュベットに入れて動的光散乱粒度分析器で分析し、その結果を図6に示す。
マイクロRNA(miRNA)の一種であるmiR125を発現しているヒト神経膠芽腫(human glioblastoma)細胞としてのA172細胞と、発現しないA172細胞を用意した。各細胞から実施例1と同様の方法でマイクロベシクルを製造した。miR125を発現する細胞に由来するマイクロベシクルはmiR125を負荷しているものと予想した。
実施例1と同様の方法によって血管内皮細胞HUVECからマイクロベシクルを製造した。血管内皮細胞HUVECはVEGF受容体を表面に発現しているので、HUVECに由来するマイクロベシクルもVEGF受容体を有するものと予想した。
センスICAM−1 cDNAとアンチセンスICAM−1cDNAを得るために、ヒト前立腺癌細胞株としてのPC3細胞(ATCC No.CRL−1435)の全体RNAを使用した。センスプライマー(primer)としての5’−GATCGGATCCTCAGCCTCGCTAT−GGCTCCCAGCA−3’とアンチセンスプライマーとしての5’−GCTAGGATCCCGGGATA−GGTTCAGGGAGGCG−3’を用いて逆転写PCR(reverse transcription PCR)を介してそれぞれICAM−1センス、アンチセンスcDNAを得た。1.6kbの大きさを有するICAM−1 cDNAはアガロスゲル(agarose)泳動によって分離した。分離したcDNAは制限酵素(restriction enzyme)Bam HIで切断し、プラスミドpCEP4(Invitrogen No.V04450)もBamHIで切断した後、接合酵素(ligase)を処理してpCEP4とICAM−1 cDNAとが接合されるようにした。それぞれセンスICAM−1とアンチセンスICAM−1 cDNAが入っているpCEP4ベクターをヒト線維芽細胞腫としてのHT1080(ATCC No.CCL−12)にFuGENE6トランスフェクション試薬(transfection reagent)Roche No.1815091)を用いて形質転換した。これらの細胞は250μg/mLのハイグロマイシン(hygromycin)B抗生剤条件で培養した。
図1に示した模式図に従い、単核球又はマクロファージからマイクロベシクルを製造した。図1において押出法と密度勾配の方法を使用し、押出段階で抗癌薬物を投与して薬物を負荷した。
実施例9と同様の方法で単核球から製造したマイクロベシクルをグロー放電炭素コート銅グリッドで3分間吸着させた。前記グリッドを蒸留水で洗浄した後、2%酢酸ウラニルで1分間染色した。JEM101電子顕微鏡で観察し、その結果を図12に示す。
図1に示した模式図に従い、単核球又はマクロファージからマイクロベシクルを製造した。図1において押出法と密度勾配の方法を使用し、細胞水準で物質を負荷した。
実施例9の方法においてドキソルビシン溶液を添加する段階を省略し、電気穿孔法で緑色蛍光タンパク質プラスミド(Green Fluorescence Protein、GFP、Clontech No.6085−1)又は赤色蛍光タンパク質プラスミド(Red Fluorescence Protein、RFP、Clontech No.632465)を注入した単核球を用いて、GFP又はRFPが負荷されたマイクロベシクルを製造して使用した。
単核球を5×107cells/wellとなるようにPBSに入れ、5μMとなるようにDiI(1,1'-dioctadecyl-3,3,3'3'-tetramethylindocarbocyanine perchlorate、Invitrogen、No.V22885)染色剤を入れた。30分間37℃で培養した後、500×gで単核球を遠心分離し、Qdot 705を電気穿孔法で注入した。ドキソルビシン溶液を添加する段階を省略した実施例9の方法で、前記単核球からマイクロベシクルを製造して使用した。これと同時に、前記Qdot 705のないマイクロベシクルも実施例1と同様の方法によって製造した。
実施例9の方法においてドキソルビシン溶液を添加する段階を省略し、電気穿孔法でRNA分解酵素A(RNase A、Sigma、No.R4875)を注入した単核球を用いて、RNase Aが負荷されたマイクロベシクルを製造して使用した。
マクロファージを5×106cells/mLの濃度でPBS溶液に懸濁し、ドキソルビシン溶液の代わりに抗炎症薬物としてのデキサメタゾン(Sigma、No.D2915)400μg/mL溶液を用いて、実施例9と同様の方法によって、デキサメタゾンが負荷されたマイクロベシクルを得た。
直径35mmの細胞培養プレートに0.1%ゼラチンをコートし、ヒト血管細胞HUVECを1×105となるように接種した後、12時間培養して細胞が満ちるように(confluent)した。細胞が満ちた後、200p tipを用いてスクラッチ(scratch)を与え、10ng/mLとなるようにTNF−αを入れ、6時間培養して細胞を成長させた。
マウス大腸癌26細胞株(mouse colon 26 cell line)1×106細胞[Cancer Res. 57; 1625-1629 (1997)]をマウスの皮膚下に注射し、5日間培養した。
実施例18で実験したマウスから採取した癌組織のうち、PBS、ドキソルビシンを負荷したマイクロベシクルを処理した癌組織を4%パラホルムアルデヒドに浸して24時間固定した。固定した癌組織を70%エタノール(ethanol)に1時間ずつ1回、95%エタノールに1時間ずつ4回、100%エタノールに1時間ずつ3回、100%キシレン(xylen)に1時間ずつ3回浸して脱水反応(dehydration)をさせた。その後、パラフィン(paraffin)に入れて固定した。パラフィンで固定された癌組織を4μmの厚さに切断し、スライドガラスに付着させた。付着した組織を60℃で1時間保管してパラフィンを溶かした。溶かした組織を100%キシレンに1分ずつ3回、100%エタノールに1分ずつ4回、95%エタノールに1分ずつ3回、最後に流れる水に5分間保管して水和反応(hydration)を行った。
前記実施例18で使用したマウス大腸癌26細胞株1×106細胞をマウスの皮膚下に注射し、5日間培養した。
前記実施例18で使用したマウス大腸癌26細胞株1×106細胞をマウスの皮膚下に注射し、5日間培養した。
前記実施例18で使用したマウス大腸癌26細胞株1×106細胞をマウスの皮膚下に注射し、5日間培養した。
実施例9の方法でドキソルビシン溶液の代わりに5−フルオロウラシル、ゲムシタビン、カルボプラチン、EGCG(Epigallocatechin gallate)溶液を用いてマクロファージから、5−フルオロウラシル、ゲムシタビン、カルボプラチン、EGCGが負荷されたマイクロベシクルを製造して使用した。
ヒト肺癌細胞株A549細胞2×106個をマトリゲル(matrigel)と混ぜてヌード(NUDE)マウスの皮膚下に注射し、25日間培養した。
マウス黒色腫細胞株B16BL6細胞2×105細胞をBNXマウスに尾静脈を介して注射し、3日間培養した。
マウスの骨髄(bone marrow)を得るために、マウスから後足の骨を取り出した後、骨に付いている筋肉塊を除去し、純粋に骨のみを分離した。1mLの注射器を用いて、骨の中に入っている骨髄組織細胞を取り出した。500×gで遠心分離して骨髄組織細胞を得た。赤血球を除去するために、RBC lysisバッファ(0.15M NH4Cl、10mM、KHCO3、0.1mM Na2EDTA、pH7.2)に細胞を入れ、室温で10分間保管した。500×gで遠心分離した後、PBSに細胞を懸濁した。前記懸濁液から実施例1の方法でマイクロベシクルを製造した。
ICAM−1アンチセンス形質転換されたHT1080細胞とICAM−1センス形質転換されたHT1080細胞から、ドキソルビシンが負荷されたマイクロベシクルを実施例9の方法で製造した。ICAM−1アンチセンス形質転換されたHT1080細胞由来マイクロベシクルはICAM−1が負荷されないが、ICAM−1センス形質転換されたHT1080細胞由来マイクロベシクルはICAM−1が負荷されている。
単核球細胞を1×106cells/mLの濃度で10mL用意し、10μMのサイトカラシンD(Sigma、No.C8273)を処理した細胞と、前記サイトカラシンDを処理していない細胞を24時間培養した。条件培地(conditioned medium)を500×gで10分間遠心分離し、得られた上層培養液を800×gで10分間2回遠心分離した。この過程で得られた上層培養液を100,000×gで2時間超遠心分離した。沈殿物をPBSで懸濁してマイクロベシクルを得た。
ヒト子宮頚部癌細胞株としてのHeLa細胞(ATCC No.CCL−2)を1×107cellsとなるように150mmのプレートに接種し、プレート内で癌細胞が80%まで満ちるように用意した。カルボキシル基(−COOH)が接合されたQdot 705(Invitrogen、No.Q21361MP)を5nMの濃度で無血清培地20mLに混ぜた後、癌細胞と共に24時間培養した。前記Qdotを処理する前に、PBSを用いて、既存の培地で培養していた細胞をよく洗浄した後、Qdotを含む培地を処理した。24時間後、条件培地を回収した後、細胞残屑(cell debris)を除去するために、800×gで10分間遠心分離を行い、連続的に3000×gで10分間遠心分離を行った。細胞残屑の除去された細胞上層液20mLを、10kDa以上の大きさのみを集める遠心分離フィルター装備を用いて3000×gで3mLとなるまで遠心分離を行った。容量5mLの超遠心分離チューブに下方からそれぞれ50%オプティプレップ1mL、5%オプティプレップ1mL、及び濃縮された3mLの条件培地を順次入れた。その後、100,000×gで2時間超遠心分離した。50%オプティプレップと5%オプティプレップとの間の層で、Qdotが負荷されたシェディングマイクロベシクルを得た。
24ウェルプレートに0.1%ゼラチンのコートされたカバーガラスを入れ、カバーガラス上にヒト血管細胞としてのHUVEC細胞を3×104の量だけ接種した後、24ウェルプレートで12時間培養した。10ng/mLとなるようにTNF−αを入れ、16時間培養した。PBSで洗浄した後、培地500μLを入れ、5μg/mLの濃度で、実施例27の方法によって分離した、 単核球由来ドキソルビシンが負荷されたシェディングマイクロベシクルを処理した後、20分間培養した。PBSで洗浄した後、無血清培地500μLを入れ、セルトラッカー溶液を5μMとなるように入れた後、30分間培養した。PBSで洗浄した後、血清のある培地を500μL仕込み、さらに30分間培養した。カバーガラスを4%パラホルムアルデヒド500μLに仕込み、室温を10分間保管した。カバーガラスをスライドガラスに付けた後、蛍光顕微鏡上で観察した。
Claims (27)
- 哺乳類の有核細胞に由来し、該細胞より小さいマイクロベシクルを含む組成物であって、
該マイクロベシクルが、該細胞から押出法を用いて人為的に製造されることにより、細胞膜のトポロジーを維持しており、
該哺乳類の有核細胞が単核球又はマクロファージであり、
該マイクロベシクルの粒径が、100〜300nmである、組成物。 - 前記哺乳類の有核細胞は特異的細胞又は組織へ誘導される細胞であることを特徴とする、請求項1記載の組成物。
- 前記哺乳類の有核細胞は疾病の治療用又は診断用物質を発現する細胞であることを特徴とする、請求項1に記載の組成物。
- 前記哺乳類の有核細胞は形質転換された細胞であることを特徴とする、請求項1に記載の組成物。
- 前記マイクロベシクルの膜は前記哺乳類の有核細胞の細胞膜以外の成分をさらに含むことを特徴とする、請求項1に記載の組成物。
- 前記細胞膜以外の成分がシクロデキストリン又はポリエチレングリコールであることを特徴とする、請求項5に記載の組成物。
- 前記マイクロベシクルの膜成分が化学的に変形されたことを特徴とする、請求項1に記載の組成物。
- 哺乳類の有核細胞に由来し、該細胞よりその大きさが小さく、疾病の治療用又は診断用物質が負荷されたマイクロベシクルを含む、薬学的組成物であって、
該マイクロベシクルが、該細胞から押出法を用いて人為的に製造されることにより、細胞膜のトポロジーを維持しており、
該哺乳類の有核細胞が単核球又はマクロファージであり、
該マイクロベシクルの粒径が、100〜300nmである、薬学的組成物。 - 前記治療用及び/又は診断用物質は前記有核細胞に由来するものであることを特徴とする、請求項8に記載の薬学的組成物。
- 前記哺乳類の有核細胞は前記治療用又は診断用物質が発現するように形質転換された有核細胞であることを特徴とする、請求項8に記載の薬学的組成物。
- 前記治療用又は診断用物質は前記有核細胞以外の外部から注入されたものであることを特徴とする、請求項8に記載の薬学的組成物。
- 疾病の治療用又は診断用物質が負荷された哺乳類の有核細胞由来マイクロベシクルの製造方法であって、細胞膜のトポロジーを維持しているマイクロベシクルを製造するために、該マイクロベシクルが該細胞から人為的に製造される、下記の段階を含む方法:
(a)哺乳類の有核細胞を含む懸濁液から押出法を用いてマイクロベシクルを製造する段階;
(b)前記懸濁液から製造されたマイクロベシクルを分離する段階;及び
(c)前記分離されたマイクロベシクルを含む懸濁液に治療用又は診断用物質を添加して培養する段階、
ここで、該哺乳類の有核細胞が単核球又はマクロファージであり、
該マイクロベシクルの粒径が、100〜300nmである。 - 疾病の治療用又は診断用物質が負荷された哺乳類の有核細胞マイクロベシクルの製造方法であって、細胞膜のトポロジーを維持しているマイクロベシクルを製造するために、該マイクロベシクルが該細胞から人為的に製造される、下記の段階を含む方法:
(a)哺乳類の有核細胞を含む懸濁液に疾病の治療用又は診断用物質を添加して培養させ、前記哺乳類の有核細胞に前記治療用又は診断用物質を負荷させる段階;及び
(b)前記治療用又は診断用物質が負荷された哺乳類の有核細胞を含む懸濁液から押出法を用いてマイクロベシクルを製造する段階、
ここで、該哺乳類の有核細胞が単核球又はマクロファージであり、
該マイクロベシクルの粒径が、100〜300nmである。 - 疾病の治療用又は診断用物質が負荷された哺乳類の有核細胞由来マイクロベシクルの製造方法であって、細胞膜のトポロジーを維持しているマイクロベシクルを製造するために、該マイクロベシクルが該細胞から人為的に製造される、下記の段階を含む方法:
(a)哺乳類の有核細胞を含む懸濁液に治療用又は診断用物質を添加して前記哺乳類の有核細胞と治療用又は診断用物質を含む混合懸濁液を得る段階;及び
(b)前記混合懸濁液から押出法を用いてマイクロベシクルを製造する段階、
ここで、該哺乳類の有核細胞が単核球又はマクロファージであり、
該マイクロベシクルの粒径が、100〜300nmである。 - 哺乳類の有核細胞に由来し、前記細胞より大きさが小さく、疾病の診断に必要なプライマー、プローブ、アンチセンス核酸又は抗体が負荷されたマイクロベシクルを含む、疾病診断用キットであって、
該マイクロベシクルが、該細胞から押出法を用いて人為的に製造されることにより、細胞膜のトポロジーを維持しており、
該哺乳類の有核細胞が単核球又はマクロファージであり、
該マイクロベシクルの粒径が、100〜300nmである、疾病診断用キット、 - 哺乳類の有核細胞に由来し、該細胞より小さいマイクロベシクルを含む組成物であって、
該マイクロベシクルが、該細胞から人為的に製造されることにより、細胞膜のトポロジーを維持しており、
該哺乳類の有核細胞が単核球又はマクロファージであり、
該マイクロベシクルの粒径が、100〜300nmである、組成物、 - 前記哺乳類の有核細胞は特異的細胞又は組織へ誘導される細胞であることを特徴とする、請求項16記載の組成物。
- 前記哺乳類の有核細胞は疾病の治療用又は診断用物質を発現する細胞であることを特徴とする、請求項16に記載の組成物。
- 前記哺乳類の有核細胞は形質転換された細胞であることを特徴とする、請求項16に記載の組成物。
- 前記マイクロベシクルの膜は前記哺乳類の有核細胞の細胞膜以外の成分をさらに含むことを特徴とする、請求項16に記載の組成物。
- 前記細胞膜以外の成分がシクロデキストリン又はポリエチレングリコールであることを特徴とする、請求項16に記載の組成物。
- 前記マイクロベシクルの膜成分が化学的に変形されたことを特徴とする、請求項16に記載の組成物。
- 哺乳類の有核細胞に由来し、該細胞よりその大きさが小さく、疾病の治療用又は診断用物質が負荷されたマイクロベシクルを含む、薬学的組成物であって、
該マイクロベシクルが、該細胞から人為的に製造されることにより、細胞膜のトポロジーを維持しており、
該哺乳類の有核細胞が単核球又はマクロファージであり、
該マイクロベシクルの粒径が、100〜300nmである、薬学的組成物。 - 前記治療用及び/又は診断用物質は前記有核細胞に由来するものであることを特徴とする、請求項23に記載の薬学的組成物。
- 前記哺乳類の有核細胞は前記治療用又は診断用物質が発現するように形質転換された有核細胞であることを特徴とする、請求項23に記載の薬学的組成物。
- 前記治療用又は診断用物質は前記有核細胞以外の外部から注入されたものであることを特徴とする、請求項23に記載の薬学的組成物。
- 哺乳類の有核細胞に由来し、前記細胞より大きさが小さく、疾病の診断に必要なプライマー、プローブ、アンチセンス核酸又は抗体が負荷されたマイクロベシクルを含む、疾病診断用キットであって、
該マイクロベシクルが、該細胞から人為的に製造されることにより、細胞膜のトポロジーを維持しており、
該哺乳類の有核細胞が単核球又はマクロファージであり、
該マイクロベシクルの粒径が、100〜300nmである、疾病診断用キット。
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
KR10-2009-0059947 | 2009-07-01 | ||
KR20090059947 | 2009-07-01 | ||
PCT/KR2010/004277 WO2011002239A2 (ko) | 2009-07-01 | 2010-07-01 | 포유류의 유핵세포에서 유래된 마이크로베시클 및 이의 용도 |
Publications (2)
Publication Number | Publication Date |
---|---|
JP2012532124A JP2012532124A (ja) | 2012-12-13 |
JP5667180B2 true JP5667180B2 (ja) | 2015-02-12 |
Family
ID=43411613
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2012518496A Active JP5667180B2 (ja) | 2009-07-01 | 2010-07-01 | 哺乳類の有核細胞に由来するマイクロベシクル及びその用途 |
Country Status (6)
Country | Link |
---|---|
US (3) | US20120177574A1 (ja) |
EP (1) | EP2450032B1 (ja) |
JP (1) | JP5667180B2 (ja) |
KR (1) | KR101314868B1 (ja) |
CN (1) | CN102596177B (ja) |
WO (1) | WO2011002239A2 (ja) |
Families Citing this family (78)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
ITRM20030376A1 (it) | 2003-07-31 | 2005-02-01 | Univ Roma | Procedimento per l'isolamento e l'espansione di cellule staminali cardiache da biopsia. |
US11660317B2 (en) | 2004-11-08 | 2023-05-30 | The Johns Hopkins University | Compositions comprising cardiosphere-derived cells for use in cell therapy |
US9249392B2 (en) | 2010-04-30 | 2016-02-02 | Cedars-Sinai Medical Center | Methods and compositions for maintaining genomic stability in cultured stem cells |
US9845457B2 (en) | 2010-04-30 | 2017-12-19 | Cedars-Sinai Medical Center | Maintenance of genomic stability in cultured stem cells |
CA2802541A1 (en) | 2010-06-23 | 2011-12-29 | Metabolex, Inc. | Compositions of 5-ethyl-2-{4-[4-(4-tetrazol-1-yl-phenoxymethyl)-thiazol-2-yl]-piperidin-1-yl}-pyrimidine |
KR101334404B1 (ko) * | 2011-04-28 | 2013-12-12 | 포항공과대학교 산학협력단 | 배아줄기세포 유래의 인공 마이크로베시클을 이용한 역분화 유도만능줄기세포의 제조방법 |
JP5872041B2 (ja) * | 2011-08-16 | 2016-03-01 | サムスン ライフ パブリック ウェルフェア ファンデーション | 幹細胞由来微小胞を含む神経生成促進用組成物 |
CN102302784B (zh) * | 2011-08-22 | 2012-12-05 | 湖北盛齐安生物科技有限公司 | 一种肿瘤化疗药物制剂及其制备方法 |
WO2013048734A1 (en) * | 2011-09-28 | 2013-04-04 | Tufts Medical Center, Inc. | Treatment and prevention of cardiovascular disease with cell derived lipid vesicles, microvesicles and exosomes |
GB201121070D0 (en) * | 2011-12-07 | 2012-01-18 | Isis Innovation | composition for delivery of biotherapeutics |
EP2861238A4 (en) | 2012-06-05 | 2016-03-16 | Capricor Inc | OPTIMIZED METHODS FOR GENERATING CARDIAC STEM CELLS FROM CARDIAC TISSUE AND THEIR USE IN CARDIAC THERAPY |
EP2882445B1 (en) | 2012-08-13 | 2019-04-24 | Cedars-Sinai Medical Center | Exosomes and micro-ribonucleic acids for tissue regeneration |
CN103654842A (zh) * | 2012-09-19 | 2014-03-26 | 重庆融海超声医学工程研究中心有限公司 | 超声监控与靶向控释系统 |
WO2014054588A1 (ja) * | 2012-10-01 | 2014-04-10 | 国立大学法人京都大学 | ナノゲル/エキソソーム複合体とdds |
US9856477B2 (en) | 2012-11-13 | 2018-01-02 | Codiak Biosciences, Inc. | Delivery of therapeutic agent |
EP2941629B1 (en) * | 2013-01-03 | 2018-10-10 | Exosome Diagnostics Inc. | Methods for isolating microvesicles |
BR112015018877A2 (pt) * | 2013-02-07 | 2017-08-22 | Externautics Spa | Método para preparar uma composição farmacêutica, e, composição farmacêutica imunogênica |
KR101473557B1 (ko) | 2013-03-29 | 2014-12-24 | 포항공과대학교 산학협력단 | 원심력을 이용한 세포유래 인공 마이크로베시클 제조 장치 |
CN105283553B (zh) | 2013-06-11 | 2021-06-25 | 克隆技术实验室有限公司 | 蛋白质富集的微泡及其制备和使用方法 |
WO2015021390A2 (en) | 2013-08-08 | 2015-02-12 | The Regents Of The University Of California | Nanoparticles leverage biological membranes to target pathogens for disease treatment and diagnosis |
JP6288635B2 (ja) * | 2013-11-01 | 2018-03-07 | 国立大学法人山形大学 | 動物細胞から細胞膜を切り出す方法、及び切り出された細胞膜 |
WO2015084677A1 (en) | 2013-12-02 | 2015-06-11 | Arytha Biosciences, Llc | Toxoid preparation and uses thereof |
CN103768602A (zh) * | 2013-12-30 | 2014-05-07 | 浙江工业大学 | 一种靶向炎症的复合物、其制备方法及应用 |
US10098839B2 (en) | 2014-03-20 | 2018-10-16 | The Regents Of The University Of California | Hydrogel toxin-absorbing or binding nanoparticles |
WO2015187502A1 (en) | 2014-06-02 | 2015-12-10 | Cellics Therapeutics, Inc. | Use of nanoparticles coated with red blood cell membranes to treat hemolytic diseases and disorders |
US11357799B2 (en) | 2014-10-03 | 2022-06-14 | Cedars-Sinai Medical Center | Cardiosphere-derived cells and exosomes secreted by such cells in the treatment of muscular dystrophy |
US10434070B2 (en) | 2015-01-02 | 2019-10-08 | Cellics Therapeutics, Inc. | Use of nanoparticles coated with red blood cell membranes to enable blood transfusion |
KR101720851B1 (ko) * | 2015-01-29 | 2017-03-28 | 포항공과대학교 산학협력단 | 세포의 지질막에서 유래된 나노소포체 및 이의 용도 |
KR101747786B1 (ko) | 2015-03-09 | 2017-06-15 | 포항공과대학교 산학협력단 | 배아줄기세포에서 유래한 인공 나노베시클을 이용하여 세포 증식을 향상시키는 방법 |
WO2016176041A1 (en) | 2015-04-29 | 2016-11-03 | The Regents Of The University Of California | Detoxification using nanoparticles |
IL256175B1 (en) | 2015-06-10 | 2024-06-01 | Univ Texas | Using exosomes to treat the disease |
EP3402543B1 (en) | 2016-01-11 | 2021-09-08 | Cedars-Sinai Medical Center | Cardiosphere-derived cells and exosomes secreted by such cells in the treatment of heart failure with preserved ejection fraction |
US11351200B2 (en) | 2016-06-03 | 2022-06-07 | Cedars-Sinai Medical Center | CDC-derived exosomes for treatment of ventricular tachyarrythmias |
EP3512948A4 (en) | 2016-09-09 | 2020-05-13 | Cornell University | ADMINISTRATION OF NUCLEIC ACIDS, PROTEINS AND SMALL MOLECULES IN VITREOUS VESICULAR BODIES |
WO2018057542A1 (en) | 2016-09-20 | 2018-03-29 | Cedars-Sinai Medical Center | Cardiosphere-derived cells and their extracellular vesicles to retard or reverse aging and age-related disorders |
CN115414335A (zh) * | 2016-09-29 | 2022-12-02 | 北卡罗来纳州立大学 | 干细胞仿生微粒 |
EP3308795A1 (en) * | 2016-10-12 | 2018-04-18 | Unicyte EV AG | A composition of extracellular vesicles (evs) and medical uses thereof |
US20190282616A1 (en) * | 2016-11-07 | 2019-09-19 | University Of Virginia Patent Foundation | Macrophages redirect phagocytosis by non-professional phagocytes and influence inflammation |
WO2018089672A1 (en) | 2016-11-09 | 2018-05-17 | Laura Perin | Extracellular vesicles from stem cells to treat and/or prevent disease |
KR20190103166A (ko) * | 2016-11-30 | 2019-09-04 | 더 리전트 오브 더 유니버시티 오브 캘리포니아 | 세포외 소포체 및 이의 방법 및 용도 |
CN106692984B (zh) * | 2016-12-08 | 2020-02-18 | 武汉大学 | 一种基于细胞源性微囊泡的肿瘤靶向递送载体及制备方法和应用 |
WO2018155979A1 (ko) * | 2017-02-24 | 2018-08-30 | (주)인핸스드바이오 | 줄기세포 유래 나노소포체 및 이를 포함하는 발모 및 육모 촉진용 조성물 |
EP3612191A4 (en) | 2017-04-19 | 2020-12-30 | Cedars-Sinai Medical Center | METHODS AND COMPOSITIONS FOR TREATING SKELETAL MUSCLE DYSTROPHY |
WO2018208728A1 (en) | 2017-05-08 | 2018-11-15 | Flagship Pioneering, Inc. | Compositions for facilitating membrane fusion and uses thereof |
CA3071553A1 (en) * | 2017-08-04 | 2019-02-07 | Ohio State Innovation Foundation | Method for producing therapeutic exosomes from nanoelectroporation and other non-endocytic cell transfection |
GB2574785A (en) | 2017-09-15 | 2019-12-25 | Jan Loetvall | Method and system for identifying membrane proteins on extracellular vesicles |
FI3684381T3 (fi) * | 2017-09-21 | 2023-01-13 | Solunulkoisten vesikkelien tuotanto yksisolususpensiossa käyttämällä kemiallisesti määriteltyä soluviljelyn elatusainetta | |
CN111655292A (zh) * | 2017-12-07 | 2020-09-11 | 旗舰先锋创新V股份有限公司 | 细胞生物制品及其治疗用途 |
US11660355B2 (en) | 2017-12-20 | 2023-05-30 | Cedars-Sinai Medical Center | Engineered extracellular vesicles for enhanced tissue delivery |
KR102184722B1 (ko) * | 2018-01-31 | 2020-12-01 | 서울대학교산학협력단 | 성체줄기세포 유래의 나노베시클 및 이의 표적 치료용 용도 |
TWI698640B (zh) * | 2018-04-23 | 2020-07-11 | 長庚醫療財團法人高雄長庚紀念醫院 | 用於檢測狼瘡性腎炎或評估狼瘡性腎炎風險的方法及其應用 |
CN108619114B (zh) * | 2018-05-02 | 2020-08-11 | 东南大学 | 一种负载地塞米松的巨噬细胞源微囊泡及其制备方法和应用 |
CN110507826B (zh) * | 2018-05-21 | 2021-10-01 | 中国科学院上海药物研究所 | 一种基于巨噬细胞的活细胞载药系统、其制备方法和应用 |
KR102111964B1 (ko) * | 2018-10-02 | 2020-05-18 | 주식회사 스템온 | 유도된 엑소좀을 포함하는 모발 재생 조성물 |
CN109498541A (zh) * | 2018-12-12 | 2019-03-22 | 福建省海西细胞生物工程有限公司 | 一种智能改善多种皮肤问题的干细胞微囊组合物 |
CN110025593B (zh) * | 2019-04-15 | 2020-10-23 | 中山大学 | 细胞微囊、载有抗癌药物的细胞微囊、其制备方法和应用 |
IL266153A (en) * | 2019-04-18 | 2019-07-31 | Aharon Anat | Extracellular vesicles derived from t cells containing a chimeric antigen receptor |
CN110093274B (zh) * | 2019-05-13 | 2020-08-11 | 山东大学 | 一种增加细胞产生的细胞外囊泡数量的挤压装置及其应用 |
CN110711249B (zh) * | 2019-09-19 | 2020-10-27 | 北京化工大学 | 一种溶酶体膜包覆纳米颗粒的制备方法 |
CN110627873B (zh) * | 2019-11-08 | 2021-03-26 | 天津医科大学 | 一种短肽exp及基于该短肽的药物递送系统和细胞外囊泡回收试剂盒 |
CN112980791B (zh) * | 2019-12-12 | 2023-05-16 | 中国科学院深圳先进技术研究院 | 一种微囊泡的生产方法、基于该微囊泡的生产方法得到的微囊泡及其应用 |
WO2021145675A1 (ko) * | 2020-01-14 | 2021-07-22 | 주식회사 엠디뮨 | 표적 단백질을 포함하는 세포 유래 베시클 및 이의 제조방법 |
CN113384597A (zh) * | 2020-03-13 | 2021-09-14 | 西比曼生物科技(上海)有限公司 | 含人体细胞衍生的细胞膜外囊泡的雾化吸入制剂、制法及其应用 |
CN111407742B (zh) * | 2020-03-30 | 2021-10-22 | 西南交通大学 | 一种抗肿瘤纳米颗粒及其制备方法和应用 |
KR20210133116A (ko) | 2020-04-28 | 2021-11-05 | 주식회사 엠디뮨 | 세포 유래 베시클의 정제 방법 |
EP4149440A1 (en) | 2020-05-11 | 2023-03-22 | Erytech Pharma | Red cell extracellular vesicles (rcevs) containing cargoes and methods of use and production thereof |
KR102236375B1 (ko) * | 2020-05-22 | 2021-04-05 | 주식회사 엠디뮨 | 단백질 항상성 조절인자가 풍부한 세포 유래 베시클 및 이의 제조 방법 |
KR102522167B1 (ko) | 2020-10-23 | 2023-04-14 | 포항공과대학교 산학협력단 | 인공 마이크로베시클 제조방법 |
WO2022087737A1 (en) * | 2020-10-28 | 2022-05-05 | Pivotal Health Sciences Inc. | Process and composition for production of organic submicrometric particles from whole biological matter |
CN112386712B (zh) * | 2020-11-09 | 2022-08-30 | 张洪 | 分子探针及其制备方法和用途 |
CN112458055B (zh) * | 2020-11-24 | 2023-12-29 | 重庆大学 | 一种基于切应力刺激作用下制备细胞微囊泡的方法 |
CN114716548A (zh) | 2021-01-05 | 2022-07-08 | (株)爱恩德生物 | 抗-fgfr3抗体及其用途 |
EP4289938A1 (en) * | 2021-02-02 | 2023-12-13 | MDimune Inc. | Cell-derived vesicles with increased cellular uptake capacity and method for producing same |
CN113943705B (zh) * | 2021-11-01 | 2023-09-19 | 北京大学口腔医学院 | 一种凋亡微囊泡及其制备方法和应用 |
CN114395531A (zh) * | 2021-12-29 | 2022-04-26 | 镇江市中西医结合医院(镇江市第二人民医院) | 一种生物活性物质或药物传递微囊泡的制备方法及其应用 |
WO2023229657A1 (en) | 2022-05-24 | 2023-11-30 | Capsugel Italy S.R.L. | Methods for processing and analyzing extracellular vesicles |
CN115404216A (zh) * | 2022-08-24 | 2022-11-29 | 中山大学附属第五医院 | 一种中性粒细胞胞外诱捕网的诱导物、诱导方法及其抑制剂 |
CN115537386A (zh) * | 2022-09-26 | 2022-12-30 | 华南理工大学 | 一种基于脱核干细胞的促修复微囊泡及其制备方法和应用 |
Family Cites Families (15)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CA2150617C (en) * | 1995-02-07 | 2001-10-30 | Universite Laval | Nanoerythrosome as bioactive agent carrier |
FR2766205B1 (fr) | 1997-07-16 | 2002-08-30 | Inst Nat Sante Rech Med | Nouveau procede de sensibilisation de cellules presentatrices d'antigene et nouveaux moyens pour la mise en oeuvre du procede |
FR2785543B1 (fr) * | 1998-11-05 | 2003-02-28 | Inst Nat Sante Rech Med | Exosomes modifies et utilisations |
GB0007150D0 (en) * | 2000-03-24 | 2000-05-17 | Lamellar Therapeutics Limited | Immunotherapeutic methods and compositions |
US20040241176A1 (en) | 2000-04-27 | 2004-12-02 | Ap Cells. Inc. | Method of producing membrane vesicles |
AU2003214566A1 (en) * | 2002-03-14 | 2003-09-22 | Anosys, Inc. | Functionalization of T cell derived vesicles and use thereof for the preparation of immunogenic pharmaceutical compositions |
US20040029240A1 (en) * | 2002-05-13 | 2004-02-12 | Acker Jesse L. | Dynamic electroporation apparatus and method |
EP1393720A1 (en) * | 2002-08-27 | 2004-03-03 | Universiteit Utrecht | Vesicle-encapsulated corticosteroids for treatment of cancer |
CN102028953B (zh) | 2004-02-02 | 2013-10-30 | 恩杰内克分子递送有限公司 | 经细菌来源的完整微细胞在体外和体内将药物靶向递送至哺乳动物细胞的组合物和方法 |
JP2008501336A (ja) * | 2004-06-02 | 2008-01-24 | ソースフアーム・インコーポレイテツド | Rnaを含有する微小胞およびそのための方法 |
EP1714642A1 (en) * | 2005-04-18 | 2006-10-25 | Bracco Research S.A. | Pharmaceutical composition comprising gas-filled microcapsules for ultrasound mediated delivery |
US20070243137A1 (en) * | 2006-04-18 | 2007-10-18 | Nanoprobes, Inc. | Cell and sub-cell methods for imaging and therapy |
ES2523098T3 (es) | 2007-10-29 | 2014-11-20 | Fresenius Medical Care Deutschland Gmbh | Microvesícula (MV) derivada de células madre para su uso en la inhibición de la apoptosis inducida por un agente citostático |
EP2547370A4 (en) * | 2010-03-17 | 2014-06-25 | Univ Texas | UNIVERSAL THERANOSTICS MANAGED BY CELLS |
WO2011147175A1 (zh) * | 2010-05-26 | 2011-12-01 | Zhang Chenyu | 细胞微粒子-siRNA复合物的制备及其在艾滋病治疗中的应用 |
-
2010
- 2010-07-01 WO PCT/KR2010/004277 patent/WO2011002239A2/ko active Application Filing
- 2010-07-01 JP JP2012518496A patent/JP5667180B2/ja active Active
- 2010-07-01 US US13/381,338 patent/US20120177574A1/en not_active Abandoned
- 2010-07-01 CN CN201080037538.XA patent/CN102596177B/zh active Active
- 2010-07-01 KR KR1020100063372A patent/KR101314868B1/ko active IP Right Grant
- 2010-07-01 EP EP10794374.8A patent/EP2450032B1/en active Active
-
2013
- 2013-10-18 US US14/058,023 patent/US20140044647A1/en not_active Abandoned
-
2018
- 2018-04-23 US US15/959,521 patent/US10675244B2/en active Active
Also Published As
Publication number | Publication date |
---|---|
KR20110002443A (ko) | 2011-01-07 |
US20140044647A1 (en) | 2014-02-13 |
US20120177574A1 (en) | 2012-07-12 |
WO2011002239A2 (ko) | 2011-01-06 |
EP2450032B1 (en) | 2018-09-05 |
WO2011002239A9 (ko) | 2011-07-28 |
WO2011002239A3 (ko) | 2011-05-26 |
EP2450032A2 (en) | 2012-05-09 |
CN102596177A (zh) | 2012-07-18 |
US10675244B2 (en) | 2020-06-09 |
EP2450032A4 (en) | 2014-03-05 |
JP2012532124A (ja) | 2012-12-13 |
US20180296483A1 (en) | 2018-10-18 |
KR101314868B1 (ko) | 2013-10-08 |
CN102596177B (zh) | 2014-05-28 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP5667180B2 (ja) | 哺乳類の有核細胞に由来するマイクロベシクル及びその用途 | |
KR101232377B1 (ko) | 세포의 원형질체에서 유래한 마이크로베시클 및 이의 용도 | |
Wu et al. | Extracellular vesicles: A bright star of nanomedicine | |
Aqil et al. | Milk exosomes-Natural nanoparticles for siRNA delivery | |
KR101752506B1 (ko) | 세균유래 마이크로베시클을 이용한 암치료 및 암진단 방법 | |
Peng et al. | Exosome: a significant nano-scale drug delivery carrier | |
Zhu et al. | Novel alternatives to extracellular vesicle-based immunotherapy–exosome mimetics derived from natural killer cells | |
Kim et al. | Extracellular vesicle mimetics: novel alternatives to extracellular vesicle-based theranostics, drug delivery, and vaccines | |
KR101720851B1 (ko) | 세포의 지질막에서 유래된 나노소포체 및 이의 용도 | |
Hood et al. | A systematic approach to exosome‐based translational nanomedicine | |
Liu et al. | Camouflaged Hybrid Cancer Cell‐Platelet Fusion Membrane Nanovesicles Deliver Therapeutic MicroRNAs to Presensitize Triple‐Negative Breast Cancer to Doxorubicin | |
Modani et al. | An updated review on exosomes: biosynthesis to clinical applications | |
Choi et al. | Targeted delivery of exosomes armed with anti-cancer therapeutics | |
Huang et al. | Research advances of engineered exosomes as drug delivery carrier | |
Desai et al. | “Bioinspired” membrane-coated nanosystems in cancer theranostics: a comprehensive review | |
Li et al. | Noninvasive platelet membrane‐coated Fe3O4 nanoparticles identify vulnerable atherosclerotic plaques | |
Mia et al. | Summary report of the 1st MOVE symposium in Málaga from 24-27th October 2023-Foster the European mobility for young scientists in extracellular vesicles research |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A977 | Report on retrieval |
Free format text: JAPANESE INTERMEDIATE CODE: A971007 Effective date: 20130809 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20130905 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20131120 |
|
A602 | Written permission of extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A602 Effective date: 20131127 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20140106 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A821 Effective date: 20140106 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20140206 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20140507 |
|
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: 20141205 |
|
A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20141211 |
|
R150 | Certificate of patent or registration of utility model |
Ref document number: 5667180 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
S111 | Request for change of ownership or part of ownership |
Free format text: JAPANESE INTERMEDIATE CODE: R313113 |
|
R350 | Written notification of registration of transfer |
Free format text: JAPANESE INTERMEDIATE CODE: R350 |
|
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 |
|
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 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |