CN115501187B - 一种金属卟啉基纳米颗粒、制备方法及应用 - Google Patents
一种金属卟啉基纳米颗粒、制备方法及应用 Download PDFInfo
- Publication number
- CN115501187B CN115501187B CN202211146493.0A CN202211146493A CN115501187B CN 115501187 B CN115501187 B CN 115501187B CN 202211146493 A CN202211146493 A CN 202211146493A CN 115501187 B CN115501187 B CN 115501187B
- Authority
- CN
- China
- Prior art keywords
- metalloporphyrin
- porphyrin
- tetra
- manganese
- carboxyphenyl
- 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
- 239000002105 nanoparticle Substances 0.000 title claims abstract description 114
- 238000002360 preparation method Methods 0.000 title claims abstract description 20
- 238000003384 imaging method Methods 0.000 claims abstract description 28
- 229910021645 metal ion Inorganic materials 0.000 claims abstract description 16
- 210000005005 sentinel lymph node Anatomy 0.000 claims abstract description 16
- 239000007864 aqueous solution Substances 0.000 claims abstract description 13
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 11
- 239000003381 stabilizer Substances 0.000 claims abstract description 7
- -1 (4-boranylphenyl) porphyrin Chemical compound 0.000 claims description 60
- 238000000502 dialysis Methods 0.000 claims description 15
- 239000000243 solution Substances 0.000 claims description 14
- 239000002202 Polyethylene glycol Substances 0.000 claims description 11
- 229920001223 polyethylene glycol Polymers 0.000 claims description 11
- 150000004033 porphyrin derivatives Chemical class 0.000 claims description 7
- 229920003171 Poly (ethylene oxide) Polymers 0.000 claims description 5
- 239000002872 contrast media Substances 0.000 claims description 5
- 238000002156 mixing Methods 0.000 claims description 5
- GVJHHUAWPYXKBD-UHFFFAOYSA-N (±)-α-Tocopherol Chemical compound OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-UHFFFAOYSA-N 0.000 claims description 4
- HHDUMDVQUCBCEY-UHFFFAOYSA-N 4-[10,15,20-tris(4-carboxyphenyl)-21,23-dihydroporphyrin-5-yl]benzoic acid Chemical compound OC(=O)c1ccc(cc1)-c1c2ccc(n2)c(-c2ccc(cc2)C(O)=O)c2ccc([nH]2)c(-c2ccc(cc2)C(O)=O)c2ccc(n2)c(-c2ccc(cc2)C(O)=O)c2ccc1[nH]2 HHDUMDVQUCBCEY-UHFFFAOYSA-N 0.000 claims description 4
- 229920001577 copolymer Polymers 0.000 claims description 4
- 239000000203 mixture Substances 0.000 claims description 4
- 239000008367 deionised water Substances 0.000 claims description 3
- 229910021641 deionized water Inorganic materials 0.000 claims description 3
- KIUKXJAPPMFGSW-DNGZLQJQSA-N (2S,3S,4S,5R,6R)-6-[(2S,3R,4R,5S,6R)-3-Acetamido-2-[(2S,3S,4R,5R,6R)-6-[(2R,3R,4R,5S,6R)-3-acetamido-2,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-2-carboxy-4,5-dihydroxyoxan-3-yl]oxy-5-hydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-3,4,5-trihydroxyoxane-2-carboxylic acid Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@H](O3)C(O)=O)O)[C@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](C(O)=O)O1 KIUKXJAPPMFGSW-DNGZLQJQSA-N 0.000 claims description 2
- IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 claims description 2
- 229920001661 Chitosan Polymers 0.000 claims description 2
- 229920002307 Dextran Polymers 0.000 claims description 2
- RVGRUAULSDPKGF-UHFFFAOYSA-N Poloxamer Chemical compound C1CO1.CC1CO1 RVGRUAULSDPKGF-UHFFFAOYSA-N 0.000 claims description 2
- 229920002845 Poly(methacrylic acid) Polymers 0.000 claims description 2
- 229920000805 Polyaspartic acid Polymers 0.000 claims description 2
- 108010020346 Polyglutamic Acid Proteins 0.000 claims description 2
- 239000004372 Polyvinyl alcohol Substances 0.000 claims description 2
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 claims description 2
- 229920002125 Sokalan® Polymers 0.000 claims description 2
- 229930003427 Vitamin E Natural products 0.000 claims description 2
- 150000005215 alkyl ethers Chemical class 0.000 claims description 2
- 229940045110 chitosan Drugs 0.000 claims description 2
- 229960002086 dextran Drugs 0.000 claims description 2
- WIGCFUFOHFEKBI-UHFFFAOYSA-N gamma-tocopherol Natural products CC(C)CCCC(C)CCCC(C)CCCC1CCC2C(C)C(O)C(C)C(C)C2O1 WIGCFUFOHFEKBI-UHFFFAOYSA-N 0.000 claims description 2
- 229920002674 hyaluronan Polymers 0.000 claims description 2
- 229960003160 hyaluronic acid Drugs 0.000 claims description 2
- FZWBNHMXJMCXLU-BLAUPYHCSA-N isomaltotriose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1OC[C@@H]1[C@@H](O)[C@H](O)[C@@H](O)[C@@H](OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C=O)O1 FZWBNHMXJMCXLU-BLAUPYHCSA-N 0.000 claims description 2
- 239000002245 particle Substances 0.000 claims description 2
- 229920001983 poloxamer Polymers 0.000 claims description 2
- 229960000502 poloxamer Drugs 0.000 claims description 2
- 229920003229 poly(methyl methacrylate) Polymers 0.000 claims description 2
- 229920002401 polyacrylamide Polymers 0.000 claims description 2
- 239000004584 polyacrylic acid Substances 0.000 claims description 2
- 108010064470 polyaspartate Proteins 0.000 claims description 2
- 229920001610 polycaprolactone Polymers 0.000 claims description 2
- 239000004632 polycaprolactone Substances 0.000 claims description 2
- 229920002643 polyglutamic acid Polymers 0.000 claims description 2
- 239000004926 polymethyl methacrylate Substances 0.000 claims description 2
- 229920000136 polysorbate Polymers 0.000 claims description 2
- 229950008882 polysorbate Drugs 0.000 claims description 2
- 229920002451 polyvinyl alcohol Polymers 0.000 claims description 2
- 229920000036 polyvinylpyrrolidone Polymers 0.000 claims description 2
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 claims description 2
- 239000001267 polyvinylpyrrolidone Substances 0.000 claims description 2
- 235000010413 sodium alginate Nutrition 0.000 claims description 2
- 239000000661 sodium alginate Substances 0.000 claims description 2
- 229940005550 sodium alginate Drugs 0.000 claims description 2
- 229940083575 sodium dodecyl sulfate Drugs 0.000 claims description 2
- 229940086735 succinate Drugs 0.000 claims description 2
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 claims description 2
- 230000001225 therapeutic effect Effects 0.000 claims description 2
- 229940046009 vitamin E Drugs 0.000 claims description 2
- 235000019165 vitamin E Nutrition 0.000 claims description 2
- 239000011709 vitamin E Substances 0.000 claims description 2
- 229920000771 poly (alkylcyanoacrylate) Polymers 0.000 claims 1
- 210000001165 lymph node Anatomy 0.000 abstract description 35
- 208000007433 Lymphatic Metastasis Diseases 0.000 abstract description 22
- 230000001394 metastastic effect Effects 0.000 abstract description 10
- 206010061289 metastatic neoplasm Diseases 0.000 abstract description 10
- 206010028980 Neoplasm Diseases 0.000 abstract description 9
- 210000004204 blood vessel Anatomy 0.000 abstract description 6
- 238000011282 treatment Methods 0.000 abstract description 6
- 230000000694 effects Effects 0.000 abstract description 3
- 206010067484 Adverse reaction Diseases 0.000 abstract description 2
- 230000006838 adverse reaction Effects 0.000 abstract description 2
- 230000017531 blood circulation Effects 0.000 abstract description 2
- 238000010254 subcutaneous injection Methods 0.000 abstract description 2
- 239000007929 subcutaneous injection Substances 0.000 abstract description 2
- 210000003462 vein Anatomy 0.000 abstract description 2
- 239000011572 manganese Substances 0.000 description 36
- 229910052748 manganese Inorganic materials 0.000 description 26
- 229960004657 indocyanine green Drugs 0.000 description 25
- MOFVSTNWEDAEEK-UHFFFAOYSA-M indocyanine green Chemical compound [Na+].[O-]S(=O)(=O)CCCCN1C2=CC=C3C=CC=CC3=C2C(C)(C)C1=CC=CC=CC=CC1=[N+](CCCCS([O-])(=O)=O)C2=CC=C(C=CC=C3)C3=C2C1(C)C MOFVSTNWEDAEEK-UHFFFAOYSA-M 0.000 description 25
- 150000004032 porphyrins Chemical class 0.000 description 24
- 239000000523 sample Substances 0.000 description 24
- PWHULOQIROXLJO-UHFFFAOYSA-N Manganese Chemical compound [Mn] PWHULOQIROXLJO-UHFFFAOYSA-N 0.000 description 20
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 15
- 210000004027 cell Anatomy 0.000 description 10
- 238000002390 rotary evaporation Methods 0.000 description 9
- 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 8
- 230000005291 magnetic effect Effects 0.000 description 8
- 229920001992 poloxamer 407 Polymers 0.000 description 8
- 239000006185 dispersion Substances 0.000 description 7
- GQUMTQCSESILQU-UHFFFAOYSA-N 2-[10,15,20-tris(2-carboxyphenyl)-21,23-dihydroporphyrin-5-yl]benzoic acid Chemical compound OC(=O)c1ccccc1-c1c2ccc(n2)c(-c2ccccc2C(O)=O)c2ccc([nH]2)c(-c2ccccc2C(O)=O)c2ccc(n2)c(-c2ccccc2C(O)=O)c2ccc1[nH]2 GQUMTQCSESILQU-UHFFFAOYSA-N 0.000 description 6
- 238000002347 injection Methods 0.000 description 6
- 239000007924 injection Substances 0.000 description 6
- 239000007788 liquid Substances 0.000 description 6
- 238000011725 BALB/c mouse Methods 0.000 description 5
- 230000005540 biological transmission Effects 0.000 description 5
- 239000010949 copper Substances 0.000 description 5
- 238000001338 self-assembly Methods 0.000 description 5
- 238000010186 staining Methods 0.000 description 5
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 4
- 241000700159 Rattus Species 0.000 description 4
- 229910052802 copper Inorganic materials 0.000 description 4
- 229960004679 doxorubicin Drugs 0.000 description 4
- 238000000799 fluorescence microscopy Methods 0.000 description 4
- 238000002595 magnetic resonance imaging Methods 0.000 description 4
- 210000002700 urine Anatomy 0.000 description 4
- 230000002792 vascular Effects 0.000 description 4
- 238000009825 accumulation Methods 0.000 description 3
- 239000013078 crystal Substances 0.000 description 3
- 239000000975 dye Substances 0.000 description 3
- 239000011259 mixed solution Substances 0.000 description 3
- 230000005298 paramagnetic effect Effects 0.000 description 3
- 238000002603 single-photon emission computed tomography Methods 0.000 description 3
- FDJUBNCEVCSIAV-UHFFFAOYSA-N tetrakis(o-aminophenyl)porphyrin Chemical compound NC1=CC=CC=C1C(C1=CC=C(N1)C(C=1C(=CC=CC=1)N)=C1C=CC(=N1)C(C=1C(=CC=CC=1)N)=C1C=CC(N1)=C1C=2C(=CC=CC=2)N)=C2N=C1C=C2 FDJUBNCEVCSIAV-UHFFFAOYSA-N 0.000 description 3
- 239000007983 Tris buffer Substances 0.000 description 2
- 238000007605 air drying Methods 0.000 description 2
- 230000009920 chelation Effects 0.000 description 2
- 208000029078 coronary artery disease Diseases 0.000 description 2
- ZYGHJZDHTFUPRJ-UHFFFAOYSA-N coumarin Chemical compound C1=CC=C2OC(=O)C=CC2=C1 ZYGHJZDHTFUPRJ-UHFFFAOYSA-N 0.000 description 2
- VFLDPWHFBUODDF-FCXRPNKRSA-N curcumin Chemical compound C1=C(O)C(OC)=CC(\C=C\C(=O)CC(=O)\C=C\C=2C=C(OC)C(O)=CC=2)=C1 VFLDPWHFBUODDF-FCXRPNKRSA-N 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- 125000000524 functional group Chemical group 0.000 description 2
- 238000001727 in vivo Methods 0.000 description 2
- 229910052747 lanthanoid Inorganic materials 0.000 description 2
- 150000002602 lanthanoids Chemical class 0.000 description 2
- 238000001819 mass spectrum Methods 0.000 description 2
- GLVAUDGFNGKCSF-UHFFFAOYSA-N mercaptopurine Chemical compound S=C1NC=NC2=C1NC=N2 GLVAUDGFNGKCSF-UHFFFAOYSA-N 0.000 description 2
- 229910052751 metal Inorganic materials 0.000 description 2
- 239000002184 metal Substances 0.000 description 2
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 2
- 230000002285 radioactive effect Effects 0.000 description 2
- 230000001988 toxicity Effects 0.000 description 2
- 231100000419 toxicity Toxicity 0.000 description 2
- DEQANNDTNATYII-OULOTJBUSA-N (4r,7s,10s,13r,16s,19r)-10-(4-aminobutyl)-19-[[(2r)-2-amino-3-phenylpropanoyl]amino]-16-benzyl-n-[(2r,3r)-1,3-dihydroxybutan-2-yl]-7-[(1r)-1-hydroxyethyl]-13-(1h-indol-3-ylmethyl)-6,9,12,15,18-pentaoxo-1,2-dithia-5,8,11,14,17-pentazacycloicosane-4-carboxa Chemical compound C([C@@H](N)C(=O)N[C@H]1CSSC[C@H](NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CCCCN)NC(=O)[C@@H](CC=2C3=CC=CC=C3NC=2)NC(=O)[C@H](CC=2C=CC=CC=2)NC1=O)C(=O)N[C@H](CO)[C@H](O)C)C1=CC=CC=C1 DEQANNDTNATYII-OULOTJBUSA-N 0.000 description 1
- AWBOSXFRPFZLOP-UHFFFAOYSA-N 2,1,3-benzoxadiazole Chemical compound C1=CC=CC2=NON=C21 AWBOSXFRPFZLOP-UHFFFAOYSA-N 0.000 description 1
- RBTBFTRPCNLSDE-UHFFFAOYSA-N 3,7-bis(dimethylamino)phenothiazin-5-ium Chemical compound C1=CC(N(C)C)=CC2=[S+]C3=CC(N(C)C)=CC=C3N=C21 RBTBFTRPCNLSDE-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
- WYWHKKSPHMUBEB-UHFFFAOYSA-N 6-Mercaptoguanine Natural products N1C(N)=NC(=S)C2=C1N=CN2 WYWHKKSPHMUBEB-UHFFFAOYSA-N 0.000 description 1
- 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 1
- 201000003076 Angiosarcoma Diseases 0.000 description 1
- 201000001320 Atherosclerosis Diseases 0.000 description 1
- 206010006187 Breast cancer Diseases 0.000 description 1
- 208000026310 Breast neoplasm Diseases 0.000 description 1
- GAGWJHPBXLXJQN-UORFTKCHSA-N Capecitabine Chemical compound C1=C(F)C(NC(=O)OCCCCC)=NC(=O)N1[C@H]1[C@H](O)[C@H](O)[C@@H](C)O1 GAGWJHPBXLXJQN-UORFTKCHSA-N 0.000 description 1
- GAGWJHPBXLXJQN-UHFFFAOYSA-N Capecitabine Natural products C1=C(F)C(NC(=O)OCCCCC)=NC(=O)N1C1C(O)C(O)C(C)O1 GAGWJHPBXLXJQN-UHFFFAOYSA-N 0.000 description 1
- DLGOEMSEDOSKAD-UHFFFAOYSA-N Carmustine Chemical compound ClCCNC(=O)N(N=O)CCCl DLGOEMSEDOSKAD-UHFFFAOYSA-N 0.000 description 1
- 206010008342 Cervix carcinoma Diseases 0.000 description 1
- 206010009944 Colon cancer Diseases 0.000 description 1
- 208000001333 Colorectal Neoplasms Diseases 0.000 description 1
- 229920001651 Cyanoacrylate Polymers 0.000 description 1
- UHDGCWIWMRVCDJ-CCXZUQQUSA-N Cytarabine Chemical compound O=C1N=C(N)C=CN1[C@H]1[C@@H](O)[C@H](O)[C@@H](CO)O1 UHDGCWIWMRVCDJ-CCXZUQQUSA-N 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
- 208000000461 Esophageal Neoplasms Diseases 0.000 description 1
- GHASVSINZRGABV-UHFFFAOYSA-N Fluorouracil Chemical compound FC1=CNC(=O)NC1=O GHASVSINZRGABV-UHFFFAOYSA-N 0.000 description 1
- 229910052688 Gadolinium Inorganic materials 0.000 description 1
- 206010020649 Hyperkeratosis Diseases 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
- FBOZXECLQNJBKD-ZDUSSCGKSA-N L-methotrexate Chemical compound C=1N=C2N=C(N)N=C(N)C2=NC=1CN(C)C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 FBOZXECLQNJBKD-ZDUSSCGKSA-N 0.000 description 1
- GQYIWUVLTXOXAJ-UHFFFAOYSA-N Lomustine Chemical compound ClCCN(N=O)C(=O)NC1CCCCC1 GQYIWUVLTXOXAJ-UHFFFAOYSA-N 0.000 description 1
- 206010058467 Lung neoplasm malignant Diseases 0.000 description 1
- WAEMQWOKJMHJLA-UHFFFAOYSA-N Manganese(2+) Chemical compound [Mn+2] WAEMQWOKJMHJLA-UHFFFAOYSA-N 0.000 description 1
- MWCLLHOVUTZFKS-UHFFFAOYSA-N Methyl cyanoacrylate Chemical compound COC(=O)C(=C)C#N MWCLLHOVUTZFKS-UHFFFAOYSA-N 0.000 description 1
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 1
- 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 1
- 108010016076 Octreotide Proteins 0.000 description 1
- 206010030155 Oesophageal carcinoma Diseases 0.000 description 1
- 229930012538 Paclitaxel Natural products 0.000 description 1
- 206010061902 Pancreatic neoplasm Diseases 0.000 description 1
- 239000004698 Polyethylene Substances 0.000 description 1
- 239000004743 Polypropylene Substances 0.000 description 1
- 206010060862 Prostate cancer Diseases 0.000 description 1
- 208000000236 Prostatic Neoplasms 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
- 229940123237 Taxane Drugs 0.000 description 1
- FOCVUCIESVLUNU-UHFFFAOYSA-N Thiotepa Chemical compound C1CN1P(N1CC1)(=S)N1CC1 FOCVUCIESVLUNU-UHFFFAOYSA-N 0.000 description 1
- 208000007536 Thrombosis Diseases 0.000 description 1
- 208000006105 Uterine Cervical Neoplasms Diseases 0.000 description 1
- 206010057469 Vascular stenosis 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
- 229940122803 Vinca alkaloid Drugs 0.000 description 1
- 229940045799 anthracyclines and related substance Drugs 0.000 description 1
- 239000012736 aqueous medium Substances 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- VSJKWCGYPAHWDS-FQEVSTJZSA-N camptothecin Chemical compound C1=CC=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)[C@]5(O)CC)C4=NC2=C1 VSJKWCGYPAHWDS-FQEVSTJZSA-N 0.000 description 1
- 229960004117 capecitabine Drugs 0.000 description 1
- 229960004562 carboplatin Drugs 0.000 description 1
- 190000008236 carboplatin Chemical compound 0.000 description 1
- 230000007211 cardiovascular event Effects 0.000 description 1
- 229960005243 carmustine Drugs 0.000 description 1
- 201000010881 cervical cancer Diseases 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 238000002512 chemotherapy Methods 0.000 description 1
- 230000004087 circulation Effects 0.000 description 1
- 229960004316 cisplatin Drugs 0.000 description 1
- DQLATGHUWYMOKM-UHFFFAOYSA-L cisplatin Chemical compound N[Pt](N)(Cl)Cl DQLATGHUWYMOKM-UHFFFAOYSA-L 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 229960000956 coumarin Drugs 0.000 description 1
- 235000001671 coumarin Nutrition 0.000 description 1
- 229940109262 curcumin Drugs 0.000 description 1
- 235000012754 curcumin Nutrition 0.000 description 1
- 239000004148 curcumin Substances 0.000 description 1
- 229960000684 cytarabine Drugs 0.000 description 1
- 229960000975 daunorubicin Drugs 0.000 description 1
- 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 1
- 230000007547 defect Effects 0.000 description 1
- 238000003745 diagnosis Methods 0.000 description 1
- VFLDPWHFBUODDF-UHFFFAOYSA-N diferuloylmethane Natural products C1=C(O)C(OC)=CC(C=CC(=O)CC(=O)C=CC=2C=C(OC)C(O)=CC=2)=C1 VFLDPWHFBUODDF-UHFFFAOYSA-N 0.000 description 1
- 238000002224 dissection Methods 0.000 description 1
- 238000010494 dissociation reaction Methods 0.000 description 1
- 230000005593 dissociations Effects 0.000 description 1
- 229960003668 docetaxel Drugs 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 229960001904 epirubicin Drugs 0.000 description 1
- 201000004101 esophageal cancer Diseases 0.000 description 1
- HQPMKSGTIOYHJT-UHFFFAOYSA-N ethane-1,2-diol;propane-1,2-diol Chemical compound OCCO.CC(O)CO HQPMKSGTIOYHJT-UHFFFAOYSA-N 0.000 description 1
- 229960000390 fludarabine Drugs 0.000 description 1
- GIUYCYHIANZCFB-FJFJXFQQSA-N fludarabine phosphate Chemical compound C1=NC=2C(N)=NC(F)=NC=2N1[C@@H]1O[C@H](COP(O)(O)=O)[C@@H](O)[C@@H]1O GIUYCYHIANZCFB-FJFJXFQQSA-N 0.000 description 1
- 229960002949 fluorouracil Drugs 0.000 description 1
- SYTBZMRGLBWNTM-UHFFFAOYSA-N flurbiprofen Chemical compound FC1=CC(C(C(O)=O)C)=CC=C1C1=CC=CC=C1 SYTBZMRGLBWNTM-UHFFFAOYSA-N 0.000 description 1
- 229960002390 flurbiprofen Drugs 0.000 description 1
- UIWYJDYFSGRHKR-UHFFFAOYSA-N gadolinium atom Chemical compound [Gd] UIWYJDYFSGRHKR-UHFFFAOYSA-N 0.000 description 1
- GFSTXYOTEVLASN-UHFFFAOYSA-K gadoteric acid Chemical compound [Gd+3].OC(=O)CN1CCN(CC([O-])=O)CCN(CC([O-])=O)CCN(CC([O-])=O)CC1 GFSTXYOTEVLASN-UHFFFAOYSA-K 0.000 description 1
- 206010017758 gastric cancer Diseases 0.000 description 1
- 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 1
- 229960005277 gemcitabine Drugs 0.000 description 1
- 238000004896 high resolution mass spectrometry Methods 0.000 description 1
- 229960000908 idarubicin Drugs 0.000 description 1
- 238000002075 inversion recovery Methods 0.000 description 1
- 208000032839 leukemia Diseases 0.000 description 1
- 239000002502 liposome Substances 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
- 201000005202 lung cancer Diseases 0.000 description 1
- 208000020816 lung neoplasm Diseases 0.000 description 1
- 210000001365 lymphatic vessel Anatomy 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 description 1
- 229910001437 manganese ion Inorganic materials 0.000 description 1
- 239000002609 medium Substances 0.000 description 1
- 201000001441 melanoma Diseases 0.000 description 1
- 229960001428 mercaptopurine Drugs 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 231100000783 metal toxicity Toxicity 0.000 description 1
- 150000002739 metals Chemical class 0.000 description 1
- 229960000485 methotrexate Drugs 0.000 description 1
- 229960000907 methylthioninium chloride Drugs 0.000 description 1
- 238000001000 micrograph Methods 0.000 description 1
- 229960001156 mitoxantrone 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
- 208000010125 myocardial infarction Diseases 0.000 description 1
- OSTGTTZJOCZWJG-UHFFFAOYSA-N nitrosourea Chemical compound NC(=O)N=NO OSTGTTZJOCZWJG-UHFFFAOYSA-N 0.000 description 1
- 239000002405 nuclear magnetic resonance imaging agent Substances 0.000 description 1
- 229960002700 octreotide Drugs 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 229960001756 oxaliplatin Drugs 0.000 description 1
- DWAFYCQODLXJNR-BNTLRKBRSA-L oxaliplatin Chemical compound O1C(=O)C(=O)O[Pt]11N[C@@H]2CCCC[C@H]2N1 DWAFYCQODLXJNR-BNTLRKBRSA-L 0.000 description 1
- 229960001592 paclitaxel Drugs 0.000 description 1
- NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 1
- 201000002528 pancreatic cancer Diseases 0.000 description 1
- 208000008443 pancreatic carcinoma Diseases 0.000 description 1
- 229960005079 pemetrexed Drugs 0.000 description 1
- QOFFJEBXNKRSPX-ZDUSSCGKSA-N pemetrexed Chemical compound C1=N[C]2NC(N)=NC(=O)C2=C1CCC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 QOFFJEBXNKRSPX-ZDUSSCGKSA-N 0.000 description 1
- 238000012831 peritoneal equilibrium test Methods 0.000 description 1
- 238000002428 photodynamic therapy Methods 0.000 description 1
- 239000003504 photosensitizing agent Substances 0.000 description 1
- 239000012221 photothermal agent Substances 0.000 description 1
- 229910052697 platinum Inorganic materials 0.000 description 1
- 229920001993 poloxamer 188 Polymers 0.000 description 1
- 229920000747 poly(lactic acid) Polymers 0.000 description 1
- 229920001281 polyalkylene Polymers 0.000 description 1
- 229920000573 polyethylene Polymers 0.000 description 1
- 239000004626 polylactic acid Substances 0.000 description 1
- 229920001155 polypropylene Polymers 0.000 description 1
- 238000012636 positron electron tomography Methods 0.000 description 1
- 238000012877 positron emission topography Methods 0.000 description 1
- 238000004393 prognosis Methods 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 239000001022 rhodamine dye Substances 0.000 description 1
- 150000003384 small molecules Chemical class 0.000 description 1
- 201000011549 stomach cancer Diseases 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
- 229960001052 streptozocin Drugs 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- DKPFODGZWDEEBT-QFIAKTPHSA-N taxane Chemical class C([C@]1(C)CCC[C@@H](C)[C@H]1C1)C[C@H]2[C@H](C)CC[C@@H]1C2(C)C DKPFODGZWDEEBT-QFIAKTPHSA-N 0.000 description 1
- 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 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- ANRHNWWPFJCPAZ-UHFFFAOYSA-M thionine Chemical compound [Cl-].C1=CC(N)=CC2=[S+]C3=CC(N)=CC=C3N=C21 ANRHNWWPFJCPAZ-UHFFFAOYSA-M 0.000 description 1
- 229960001196 thiotepa Drugs 0.000 description 1
- 229960003087 tioguanine Drugs 0.000 description 1
- MNRILEROXIRVNJ-UHFFFAOYSA-N tioguanine Chemical compound N1C(N)=NC(=S)C2=NC=N[C]21 MNRILEROXIRVNJ-UHFFFAOYSA-N 0.000 description 1
- 238000004627 transmission electron microscopy Methods 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
- 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 1
- 229960004528 vincristine Drugs 0.000 description 1
- 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 1
- GBABOYUKABKIAF-GHYRFKGUSA-N vinorelbine Chemical compound C1N(CC=2C3=CC=CC=C3NC=22)CC(CC)=C[C@H]1C[C@]2(C(=O)OC)C1=CC([C@]23[C@H]([C@]([C@H](OC(C)=O)[C@]4(CC)C=CCN([C@H]34)CC2)(O)C(=O)OC)N2C)=C2C=C1OC GBABOYUKABKIAF-GHYRFKGUSA-N 0.000 description 1
- 229960002066 vinorelbine Drugs 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
Images
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
- A61K47/54—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic compound
- A61K47/545—Heterocyclic compounds
- A61K47/546—Porphyrines; Porphyrine with an expanded ring system, e.g. texaphyrine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K49/00—Preparations for testing in vivo
- A61K49/001—Preparation for luminescence or biological staining
- A61K49/0013—Luminescence
- A61K49/0017—Fluorescence in vivo
- A61K49/005—Fluorescence in vivo characterised by the carrier molecule carrying the fluorescent agent
- A61K49/0052—Small organic molecules
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K49/00—Preparations for testing in vivo
- A61K49/001—Preparation for luminescence or biological staining
- A61K49/0063—Preparation for luminescence or biological staining characterised by a special physical or galenical form, e.g. emulsions, microspheres
- A61K49/0069—Preparation for luminescence or biological staining characterised by a special physical or galenical form, e.g. emulsions, microspheres the agent being in a particular physical galenical form
- A61K49/0089—Particulate, powder, adsorbate, bead, sphere
- A61K49/0091—Microparticle, microcapsule, microbubble, microsphere, microbead, i.e. having a size or diameter higher or equal to 1 micrometer
- A61K49/0093—Nanoparticle, nanocapsule, nanobubble, nanosphere, nanobead, i.e. having a size or diameter smaller than 1 micrometer, e.g. polymeric nanoparticle
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K49/00—Preparations for testing in vivo
- A61K49/04—X-ray contrast preparations
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K49/00—Preparations for testing in vivo
- A61K49/06—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations
- A61K49/08—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations characterised by the carrier
- A61K49/10—Organic compounds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K49/00—Preparations for testing in vivo
- A61K49/06—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations
- A61K49/18—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations characterised by a special physical form, e.g. emulsions, microcapsules, liposomes
- A61K49/1818—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations characterised by a special physical form, e.g. emulsions, microcapsules, liposomes particles, e.g. uncoated or non-functionalised microparticles or nanoparticles
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K49/00—Preparations for testing in vivo
- A61K49/22—Echographic preparations; Ultrasound imaging preparations ; Optoacoustic imaging preparations
- A61K49/221—Echographic preparations; Ultrasound imaging preparations ; Optoacoustic imaging preparations characterised by the targeting agent or modifying agent linked to the acoustically-active agent
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K49/00—Preparations for testing in vivo
- A61K49/22—Echographic preparations; Ultrasound imaging preparations ; Optoacoustic imaging preparations
- A61K49/222—Echographic preparations; Ultrasound imaging preparations ; Optoacoustic imaging preparations characterised by a special physical form, e.g. emulsions, liposomes
- A61K49/225—Microparticles, microcapsules
-
- 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
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/141—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers
- A61K9/146—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers with organic macromolecular compounds
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
Landscapes
- Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Radiology & Medical Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Medicinal Chemistry (AREA)
- Biomedical Technology (AREA)
- Acoustics & Sound (AREA)
- Pharmacology & Pharmacy (AREA)
- Nanotechnology (AREA)
- Physics & Mathematics (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
Abstract
本发明涉及一种金属卟啉基纳米颗粒、制备方法及应用。所述制备方法为：将金属卟啉衍生物滴加至含有表面稳定剂的水溶液，经透析后，即得到所述金属卟啉基纳米颗粒。本发明所述的金属卟啉基纳米颗粒在通过局部皮下注射后，能快速到达并滞留在前哨淋巴结，并通过单模态或者多模态成像区分正常淋巴结和转移性淋巴结以此诊断肿瘤淋巴结转移；同时金属卟啉基纳米颗粒通过尾静脉注射后，具有较长的血液循环时间，可以实现血管和肿瘤的成像和治疗。本发明所述的金属卟啉基纳米颗粒未见明显的金属离子脱螯合现象和不良反应，且水分散性佳、成像效果好。
Description
技术领域
本发明属于医药技术领域，具体涉及一种金属卟啉基纳米颗粒、制备方法及应用。
背景技术
前哨淋巴结作为肿瘤引流的第一个淋巴结，其转移状态对于指导肿瘤治疗和改善预后具有至关重要的作用。由于淋巴结转移很难鉴别诊断，目前临床上只有淋巴结示踪剂在使用，而无获批的淋巴结转移诊断造影剂。目前临床使用的传统示踪剂(如磁共振造影剂Gd-DTPA或Gd-DOTA、亚甲蓝或吲哚菁绿)用于淋巴结转移成像存在以下不足：其多为小分子造影剂，倾向于重新吸收回毛细血管而非毛细淋巴管，并且在淋巴结中的保留时间不足；顺磁性金属离子(如钆)的不稳定螯合会引起金属毒性等。
目前金属卟啉及其衍生物具有独特的优势：首先高的配位稳定性能有效避免金属解离带来的毒性风险；其次，卟啉种类丰富，如不同的官能团取代卟啉大环的中间位或β位以产生各种功能卟啉衍生物或者卟啉与不同的金属配位可以产生不同成像功能，包括荧光、光声、PET、SPECT和MR成像等；再次，卟啉及其衍生物可以作为光学疗法中的光敏剂、光热剂；最后，卟啉均表现出深色，具有染色示踪淋巴结的潜力。
虽然金属卟啉及其衍生物自身性能优异，然而大多卟啉或者金属卟啉衍生物因具有大的共轭结构而水溶性差，生物利用度低，这也大大限制了其在生物医学中的应用。
故基于此，提出本发明技术方案。
发明内容
为了解决现有技术存在的问题，本发明提供了一种金属卟啉基纳米颗粒、制备方法及应用。
本发明的方案是提供一种金属卟啉基纳米颗粒的制备方法，其特征在于，所述制备方法为：将金属卟啉衍生物滴加至含有表面稳定剂的水溶液，经透析后，即得到所述金属卟啉基纳米颗粒；其中：
所述金属卟啉衍生物由卟啉衍生物与金属离子构成，所述卟啉衍生物如式(I)所示：
所述R1、R2、R3、R4至少存在一个且最多四个，R1、R2、R3、R4为A1～A15所示的官能团中的任意一种。
优选地，所述金属离子为顺磁性金属离子、放射性金属离子或镧系发光金属离子。
优选地，所述顺磁性金属离子为Gd3+、Mn3+、Mn2+或Fe3+中的一种；所述放射性金属离子为64Cu、68Ga、86Y、89Zr、或99Tc中的一种；所述镧系发光金属离子为Tb3+、Nd3+、Eu3+、Dy3+、Sm3 +、Er3+中的一种。
优选地，所述制备方法为：将金属卟啉衍生物与掺杂功能性分子的溶液混合后，滴加至含有表面稳定剂的水溶液，经透析后，即得到所述金属卟啉基纳米颗粒；其中，所述功能性分子为成像或治疗性分子。
具体的，所述功能性分子包括苯并双噻二唑(BBTD)类染料、氟硼吡咯类、苯并呋咱类化合物、吲哚菁绿、花菁类染料、香豆素类染料、罗丹明类染料、紫杉烷类(如紫杉醇、多西他赛)、长春花生物碱(如长春碱、长春新碱、长春瑞滨)、蒽环类(阿霉素、柔红霉素、伊达比星、表柔比星)、铂类药物(如顺铂、卡铂、奥沙利铂)、5-氟尿嘧啶、6-巯基嘌呤、阿糖胞苷、卡培他滨、氟达拉滨、吉西他滨、甲氨蝶呤、培美曲塞、米托蒽醌、喷司他丁、硫代鸟嘌呤、喜树碱、噻替帕、奥曲胺、亚硝基脲链脲佐菌素、卡莫斯汀、洛莫斯汀、姜黄素、氟比洛芬等。
优选地，所述表面稳定剂为聚乙烯吡咯烷酮、聚乙烯醇、聚乙二醇、二硬脂酰磷脂酰乙醇胺-聚乙二醇、聚环氧乙烷-聚环氧丙烷-聚环氧乙烷嵌段物、泊洛沙姆，泊洛沙明、聚环氧乙烷、聚氧乙烯烷基醚、聚丙烯酸、维生素E聚乙二醇琥珀酸酯、葡聚糖、透明质酸、壳聚糖、海藻酸钠、聚山梨醇酯、十二烷基硫酸钠、聚氰基丙烯酸烷酯、聚乳酸羟基乙酸-聚乙二醇共聚物、聚乳酸-聚乙二醇共聚物、聚己内酯-聚乙二醇共聚物、脂质体、聚乳酸、聚乳酸-羟基乙酸共聚物、聚己内酯、聚天冬氨酸、聚(甲基丙烯酸)、聚丙烯酰胺、聚(甲基丙烯酸甲酯)或聚谷氨酸中的一种。
优选地，所述透析的介质为去离子水，透析的时间为2～3d，透析袋分子量为3～50kDa。
优选地，所述金属卟啉基纳米颗粒的粒径为5～500nm。
基于相同的技术构思，本发明的再提供一种由上述制备方法得到的金属卟啉基纳米颗粒。
所述金属卟啉基纳米颗粒可用于进一步制备造影剂，并应用于成像方面，如单模态成像MRI、PET、SPECT、光声成像、荧光成像以及多模态成像SPECT/MR、PET/MR、荧光/MR、光声/MR、PET/荧光、光声/荧光、光声/PET。更具体的，能够应用在血管相关疾病、肿瘤和淋巴结成像及治疗中。所述的血管相关疾病包括心肌梗死、冠心病、血管狭窄、动脉粥样硬化斑块、血栓以及肿瘤血管、血管肉瘤、冠心病；所述的肿瘤包括肺癌、结直肠癌、肝癌、胃癌、乳腺癌、食管癌、胰腺癌、前列腺癌、宫颈癌、白血病、黑色素瘤；所述的淋巴结成像包括淋巴结定位、淋巴结转移诊断、淋巴结染色示踪；所述的治疗包括光热治疗、光动治疗、化疗。
本发明的有益效果为：
1、本发明所述的金属卟啉基纳米颗粒在通过局部皮下注射后，能快速到达并滞留在前哨淋巴结，并通过单模态或者多模态成像区分正常淋巴结和转移性淋巴结以此诊断肿瘤淋巴结转移；同时金属卟啉基纳米颗粒静脉注射后，具有较长的血液循环时间，可以实现血管和肿瘤的成像和治疗。
2、本发明所述的金属卟啉基纳米颗粒为观察到未见明显的金属离子脱螯合现象和不良反应，且水分散性佳、成像效果好。
附图说明
为了更清楚地说明本发明实施例或现有技术中的技术方案，下面将对实施例或现有技术描述中所需要使用的附图作简单地介绍，显而易见地，下面描述中的附图仅仅是本发明的一些实施例，对于本领域普通技术人员来讲，在不付出创造性劳动的前提下，还可以根据这些附图获得其他的附图。
图1是本发明的四(硼酸基苯基)卟啉锰纳米颗粒的透射电镜图。
图2是本发明的四(硼酸基苯基)卟啉锰纳米颗粒的弛豫效能图。
图3是本发明的四(硼酸基苯基)卟啉锰纳米颗粒成像淋巴结转移。
图4是本发明的四(硼酸基苯基)卟啉锰纳米颗粒染色淋巴结。
图5是本发明的四(硼酸基苯基)卟啉锰纳米颗粒成像血管。
图6是本发明的四(羧基苯基)卟啉锰纳米颗粒水中稳定分散图。
图7是本发明四(羧基苯基)卟啉锰纳米颗粒经体内循环后尿液的质谱图。
图8是本发明的吲哚菁绿/四(羧基苯基)卟啉锰纳米颗粒的透射电镜图。
图9吲哚菁绿/四(羧基苯基)卟啉锰纳米颗粒磁共振成像淋巴结转移。
图10吲哚菁绿/四(羧基苯基)卟啉锰纳米颗粒荧光成像淋巴结转移。
图11吲哚菁绿/四(羧基苯基)卟啉锰纳米颗粒染色淋巴结。
具体实施方式
为使本发明的目的、技术方案和优点更加清楚，下面将对本发明的技术方案进行详细的描述。显然，所描述的实施例仅仅是本发明一部分实施例，而不是全部的实施例。基于本发明中的实施例，本领域普通技术人员在没有做出创造性劳动的前提下所得到的所有其它实施方式，都属于本发明所保护的范围。
实施例1
本实施例提供一种四(硼酸基苯基)卟啉锰纳米颗粒的制备方法，具体为：
称取四(硼酸基苯基)卟啉锰(30mg)溶解在3mL的N-N二甲基甲酰胺中，在探头超声作用(350W，开/关循环:30s/5s)下滴加到Pluronic F127水溶液(2mg/mL，15mL)，自组装形成纳米颗粒，将所述纳米颗粒用50kD的透析袋透析3d以纯化样品，最后旋转蒸发浓缩收集得到四(硼酸基苯基)卟啉锰纳米颗。
实施例2
本实施例提供一种5-(羧基苯基)卟啉锰纳米颗粒的制备方法，具体为：
称取5-(羧基苯基)卟啉锰(30mg)溶解在3mL的N-N二甲基甲酰胺中，在探头超声作用(350W，开/关循环:30s/5s)下滴加到Pluronic F127水溶液(2mg/mL，15mL)，自组装形成纳米颗粒，将所述纳米颗粒用50kD的透析袋透析3d以纯化样品，最后旋转蒸发浓缩收集得到5-(羧基苯基)卟啉锰纳米颗。
实施例3
本实施例提供一种5,10-二(羧基苯基)卟啉锰纳米颗粒的制备方法，具体为：
称取5,10-二(羧基苯基)卟啉锰(30mg)溶解在3mL的N-N二甲基甲酰胺中，在探头超声作用(350W，开/关循环:30s/5s)下滴加到Pluronic F127水溶液(2mg/mL，15mL)，自组装形成纳米颗粒，将所述纳米颗粒用50kD的透析袋透析3d以纯化样品，最后旋转蒸发浓缩收集得到5,10-二(羧基苯基)卟啉锰纳米颗。
实施例4
本实施例提供一种5,10,15-三(羧基苯基)卟啉锰纳米颗粒的制备方法，具体为：
称取5,10,15-二(羧基苯基)卟啉锰(30mg)溶解在3mL的N-N二甲基甲酰胺中，在探头超声作用(350W，开/关循环:30s/5s)下滴加到Pluronic F127水溶液(2mg/mL，15mL)，自组装形成纳米颗粒，将所述纳米颗粒用50kD的透析袋透析3d以纯化样品，最后旋转蒸发浓缩收集得到5,10,15-三(羧基苯基)卟啉锰纳米颗。
实施例5
本实施例提供一种四(羧基苯基)卟啉锰纳米颗粒的制备方法，具体为：
称取四(羧基苯基)卟啉锰(30mg)溶解在3mL的N-N二甲基甲酰胺中，在探头超声作用(350W，开/关循环:30s/5s)下滴加到Pluronic F127水溶液(2mg/mL，15mL)，自组装形成纳米颗粒，将所述纳米颗粒用50kD的透析袋透析3d以纯化样品，最后旋转蒸发浓缩收集得到四(羧基苯基)卟啉锰纳米颗。
实施例6
本实施例提供一种阿霉素/四(羧基苯基)卟啉锰纳米颗粒的制备方法，具体为：
将阿霉素和四(羧基苯基)卟啉锰的N-N二甲基甲酰胺溶液按照摩尔比为3：1、1：1、1：3、1：6和1：9混合，在探头超声作用下(350W，开/关周期：5s/5s)，将混合溶液逐滴加入到Pluronic F127水溶液(2mg/mL)中自组装纳米颗粒，然后将所述纳米颗粒用50kD透析袋透析3d以纯化样品，最后旋转蒸发浓缩收集得到阿霉素/四(羧基苯基)卟啉锰纳米颗粒。
实施例7
本实施例提供一种四(氨基苯基)卟啉/四(羧基苯基)卟啉锰纳米颗粒的制备方法，具体为：
将四(氨基苯基)卟啉和四(羧基苯基)卟啉锰的N-N二甲基甲酰胺溶液按照摩尔比为3：1、1：1、1：3、1：6和1：9混合，在探头超声作用下(350W，开/关周期：5s/5s)，将混合溶液逐滴加入到Pluronic F127水溶液(2mg/mL)中自组装纳米颗粒。然后将纳米颗粒用50kD透析袋透析3天以纯化样品，最后旋转蒸发浓缩收集，得到四(氨基苯基)卟啉/四(羧基苯基)卟啉锰纳米颗粒。
实施例8
本实施例提供一种吲哚菁绿/四(羧基苯基)卟啉锰纳米颗粒的制备方法，具体为：
将吲哚菁绿/四(羧基苯基)卟啉锰的N-N二甲基甲酰胺溶液按照摩尔比为3：1、1：1、1：3、1：6和1：9混合，在探头超声作用下(350W，开/关周期：5s/5s)，将混合溶液逐滴加入到Pluronic F127水溶液(2mg/mL)中自组装纳米颗粒。然后将纳米颗粒用50kD透析袋透析3天以纯化样品，最后旋转蒸发浓缩收集得到吲哚菁绿/四(羧基苯基)卟啉锰纳米颗粒。
实施例9
本实施例提供一种四(硼酸基苯基)卟啉锰纳米颗粒的制备方法，具体为：
称取四(硼酸基苯基)卟啉锰(30mg)溶解在3mL的N-N二甲基甲酰胺中，在探头超声作用(350W，开/关循环:30s/5s)下滴加到Pluronic F68水溶液(2mg/mL，15mL)，自组装形成纳米颗粒，将所述纳米颗粒用50kD的透析袋透析3d以纯化样品，最后旋转蒸发浓缩收集得到四(硼酸基苯基)卟啉锰纳米颗。
试验例1
本试验例将实施例1制备的四(硼酸基苯基)卟啉锰纳米颗粒进行如下性能的检测：
(1)将四(硼酸基苯基)卟啉锰纳米颗粒经透射电镜(TEM)检测：
取适量四(硼酸基苯基)卟啉锰纳米颗粒分散液吸取10μL滴至铜网表面，室温下自然风干，然后将样品置于透射电镜下拍摄，结果如图1所示，四(硼酸基苯基)卟啉锰纳米颗粒的晶核在20纳米左右，呈现类球形形貌。
(2)四(硼酸基苯基)卟啉锰纳米颗粒的弛豫效能：
用去离子水分别稀释四(硼酸基苯基)卟啉锰纳米颗粒配置8个不同锰离子浓度样品(0.5、0.4、0.3、0.25、0.15、0.1、0.06和0.01mM)，然后用3T临床磁共振成像系统(Siemens)检测样品的T1弛豫效能，通过反转恢复(Inversion recovery，IR)序列扫描(TE＝11.7ms，TR＝30～3300ms)获取样品的T1-加权图像，然后圈值，软件计算拟合得到以T1弛豫时间的倒数(1/T1，s-1)为纵坐标以及样品浓度(mM)为横坐标的曲线，曲线的斜率即为样品的弛豫效能(r1，mM-1s-1)。结果如图2所示，四(硼酸基苯基)卟啉锰纳米颗粒的T1弛豫效能为4.97mM-1s-1。
(3)四(硼酸基苯基)卟啉锰纳米颗粒淋巴结转移成像：
首先将4T1细胞(5×105细胞/10μL PBS)通过脚垫注射到BALB/c小鼠的右腿足底，建立淋巴结转移模型，待淋巴结发生转移。通过脚垫注射四(硼酸基苯基)卟啉锰纳米颗粒，注射剂量为0.005mmol Mn/kg，通过3.0T磁共振扫描系统采集给药前和给药后1h、2h、3h、4h以及24h的淋巴结成像图。结果如图3所示，与注射前相比，给药后左侧前哨淋巴结(正常淋巴结)和右侧前哨淋巴结(转移性淋巴结)的磁共振信号强度均增强，表明四(硼酸基苯基)卟啉锰纳米颗粒在前哨淋巴结中的积累。并且正常淋巴结的T1磁共振信号强度明显高于转移性淋巴结。
(4)四(硼酸基苯基)卟啉锰纳米颗粒染色前哨淋巴结：
首先将4T1细胞(5×105细胞/10μL PBS)通过脚垫注射到BALB/c小鼠的右腿足底，建立淋巴结转移模型。待淋巴结发生转移后，通过脚垫注射四(硼酸基苯基)卟啉锰纳米颗粒，注射剂量为0.005mmol Mn/kg，1小时后解剖观察淋巴结染色情况。如图4所示，相比于没有打药组，给药四(硼酸基苯基)卟啉锰纳米颗粒后淋巴结明显染色。
(5)四(硼酸基苯基)卟啉锰纳米颗粒血管成像：
首先给SD大鼠安置留置针，扫描给药前SD大鼠的心血管(3.0T磁共振扫描系统)。然后通过留置针注射四(硼酸基苯基)卟啉锰纳米颗粒(0.05mmol Mn/kg)后，采集1min，2min，3min，10min，20min，1h，2h和24h的SD大鼠的血管成像信号图。结果如图5所示，四(硼酸基苯基)卟啉锰纳米颗粒具有长的血管成像时间以及非常清晰的血管成像效果。
试验例2
本试验例将实施例5制备的四(羧基苯基)卟啉锰纳米颗粒进行如下性能的检测：
(1)四(羧基苯基)卟啉锰纳米颗粒在水中稳定分散性。
将四(羧基苯基)卟啉锰分别超声滴加到水介质和F127水溶液，24小时后观察其稳定状态。结果如图6所示，F127稳定的四(羧基苯基)卟啉锰纳米颗粒能在水中长时间稳定分散。
(2)四(羧基苯基)卟啉锰纳米颗粒体内高螯合稳定性表征。
尾静脉注射四(羧基苯基)卟啉锰纳米颗粒(0.05mmol Mn/kg)到SD大鼠体内，用代谢笼收集2h，12h,12h和48h的尿液。用高分辨质谱分析尿液。结果如图7，尿液质谱中大量存在TCPP(Mn)分子量，表明TCPP(Mn)具有高的螯合稳定性，能避免金属离子脱螯合引发的毒性。
试验例3
本试验例将实施例8制备的吲哚菁绿/四(羧基苯基)卟啉锰纳米颗粒进行如下性能的检测：
(1)将吲哚菁绿/四(羧基苯基)卟啉锰纳米颗粒经透射电镜(TEM)检测：
取适量吲哚菁绿/四(羧基苯基)卟啉锰纳米颗粒分散液吸取10μL滴至铜网表面，室温下自然风干，然后将样品置于透射电镜下拍摄，结果如图8所示，吲哚菁绿/四(羧基苯基)卟啉锰纳米颗粒的晶核在15纳米左右，呈现类球形形貌。
(2)吲哚菁绿/四(羧基苯基)卟啉锰纳米颗粒磁共振成像淋巴结转移：
首先将4T1细胞(5×105细胞/10μL PBS)通过脚垫注射到BALB/c小鼠的右腿足底，建立淋巴结转移模型，待淋巴结发生转移。通过脚垫注射吲哚菁绿/四(羧基苯基)卟啉锰纳米颗粒，注射剂量为0.005mmol Mn/kg，通过3.0T磁共振扫描系统采集给药前和给药后0.5h、1h、2h、3h以及4h的淋巴结成像图。结果如图9所示，与注射前相比，给药后左侧前哨淋巴结(正常淋巴结)和右侧前哨淋巴结(转移性淋巴结)的磁共振信号强度均增强，表明吲哚菁绿/四(羧基苯基)卟啉锰纳米颗粒在前哨淋巴结中的积累。正常淋巴结的T1磁共振信号强度明显高于转移性淋巴结，以此可以区分正常淋巴结和转移性淋巴结。
(3)吲哚菁绿/四(羧基苯基)卟啉锰纳米颗粒荧光成像淋巴结转移：
首先将4T1细胞(5×105细胞/10μL PBS)通过脚垫注射到BALB/c小鼠的右腿足底，建立淋巴结转移模型，待淋巴结发生转移。通过脚垫注射吲哚菁绿/四(羧基苯基)卟啉锰纳米颗粒，注射剂量为0.25mg ICG/kg，通过荧光成像采集给药前和给药后0.5h、1h、2h、3h以及4h的淋巴结成像图。结果如图10所示，与注射前相比，给药后左侧前哨淋巴结(正常淋巴结)和右侧前哨淋巴结(转移性淋巴结)的磁共振信号强度均增强，表明吲哚菁绿/四(羧基苯基)卟啉锰纳米颗粒在前哨淋巴结中的积累。正常淋巴结的荧光信号强度明显低于转移性淋巴结。
(4)吲哚菁绿/四(羧基苯基)卟啉锰纳米颗粒染色前哨淋巴结：
首先将4T1细胞(5×105细胞/10μL PBS)通过脚垫注射到BALB/c小鼠的右腿足底，建立淋巴结转移模型。待淋巴结发生转移后，通过脚垫注射吲哚菁绿/四(羧基苯基)卟啉锰纳米颗粒，注射剂量为0.005mmol Mn/kg，24小时后观察淋巴结染色情况。如图11所示，相比于没有打药组，给药吲哚菁绿/四(羧基苯基)卟啉锰纳米颗粒后淋巴结明显染色。
以上所述，仅为本发明的具体实施方式，但本发明的保护范围并不局限于此，任何熟悉本技术领域的技术人员在本发明揭露的技术范围内，可轻易想到变化或替换，都应涵盖在本发明的保护范围之内。因此，本发明的保护范围应以所述权利要求的保护范围为准。
Claims (5)
1.金属卟啉基纳米颗粒在制备前哨淋巴结成像造影剂中的应用，其特征在于，所述金属卟啉基纳米颗粒的制备方法为：将金属卟啉衍生物滴加至含有表面稳定剂的水溶液，经透析后，即得到所述金属卟啉基纳米颗粒；所述金属卟啉衍生物由卟啉衍生物与金属离子构成，所述卟啉衍生物为中-四(4-硼酸基苯基)卟啉或中-四(4-羧基苯基)卟啉，金属离子为Mn3+、Mn2+。
2.金属卟啉基纳米颗粒在制备前哨淋巴结成像造影剂中的应用，其特征在于，所述金属卟啉基纳米颗粒的制备方法为：将金属卟啉衍生物与掺杂功能性分子的溶液混合后，滴加至含有表面稳定剂的水溶液，经透析后，即得到所述金属卟啉基纳米颗粒；其中，所述功能性分子为成像或治疗性分子；所述金属卟啉衍生物由卟啉衍生物与金属离子构成，所述卟啉衍生物为中-四(4-硼酸基苯基)卟啉或中-四(4-羧基苯基)卟啉，金属离子为Mn3+、Mn2 +。
3.根据权利要求1或2所述的应用，其特征在于，所述表面稳定剂为聚乙烯吡咯烷酮、聚乙烯醇、聚乙二醇、二硬脂酰磷脂酰乙醇胺-聚乙二醇、泊洛沙姆、聚环氧乙烷、聚氧乙烯烷基醚、聚丙烯酸、维生素E聚乙二醇琥珀酸酯、葡聚糖、透明质酸、壳聚糖、海藻酸钠、聚山梨醇酯、十二烷基硫酸钠、聚氰基丙烯酸烷酯、聚乳酸羟基乙酸-聚乙二醇共聚物、聚己内酯-聚乙二醇共聚物、聚乳酸-聚乙二醇共聚物、聚乳酸、聚乳酸-羟基乙酸共聚物、聚己内酯、聚天冬氨酸、聚(甲基丙烯酸)、聚丙烯酰胺、聚(甲基丙烯酸甲酯)或聚谷氨酸中的一种。
4.根据权利要求1或2所述的应用，其特征在于，所述透析的介质为去离子水，透析的时间为2～3d，透析袋分子量为3～50kDa。
5.根据权利要求1或2所述的应用，其特征在于，所述金属卟啉基纳米颗粒的粒径为5～500nm。
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202211146493.0A CN115501187B (zh) | 2022-09-20 | 2022-09-20 | 一种金属卟啉基纳米颗粒、制备方法及应用 |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202211146493.0A CN115501187B (zh) | 2022-09-20 | 2022-09-20 | 一种金属卟啉基纳米颗粒、制备方法及应用 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN115501187A CN115501187A (zh) | 2022-12-23 |
| CN115501187B true CN115501187B (zh) | 2023-07-14 |
Family
ID=84503525
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202211146493.0A Active CN115501187B (zh) | 2022-09-20 | 2022-09-20 | 一种金属卟啉基纳米颗粒、制备方法及应用 |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN115501187B (zh) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN116751369B (zh) * | 2023-07-31 | 2024-03-01 | 广东省第二人民医院（广东省卫生应急医院） | 锰掺杂金属卟啉框架材料及其制备方法和应用 |
Citations (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102573914A (zh) * | 2009-10-16 | 2012-07-11 | 大学健康网络 | 卟啉纳米囊泡 |
| CN108779124A (zh) * | 2015-12-08 | 2018-11-09 | 香港大学 | 金卟啉-peg缀合物及使用方法 |
| CN109432439A (zh) * | 2018-11-21 | 2019-03-08 | 厦门大学 | 一种具有声动力治疗效果的金属-卟啉纳米颗粒、制备方法及其应用 |
| CN109602921A (zh) * | 2019-01-21 | 2019-04-12 | 深圳市第二人民医院 | 一种锌卟啉纳米晶及其制备方法和应用 |
| WO2019243422A1 (en) * | 2018-06-19 | 2019-12-26 | Danmarks Tekniske Universitet | Solution comprising fluorescent dye as fiducial marker |
| CN110787306A (zh) * | 2018-08-02 | 2020-02-14 | 武汉凯德维斯生物技术有限公司 | 一种用于宫颈癌前哨淋巴结的纳米胶束显像剂的制备与应用 |
| CN114073922A (zh) * | 2020-08-20 | 2022-02-22 | 中国科学院苏州纳米技术与纳米仿生研究所 | 卟啉基金属-有机骨架纳米球及其制备方法与应用 |
| WO2022147533A1 (en) * | 2021-01-04 | 2022-07-07 | Nirvana Sciences Inc. | Metallohydroporphyrins for photoacoustic imaging |
-
2022
- 2022-09-20 CN CN202211146493.0A patent/CN115501187B/zh active Active
Patent Citations (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102573914A (zh) * | 2009-10-16 | 2012-07-11 | 大学健康网络 | 卟啉纳米囊泡 |
| CN108779124A (zh) * | 2015-12-08 | 2018-11-09 | 香港大学 | 金卟啉-peg缀合物及使用方法 |
| WO2019243422A1 (en) * | 2018-06-19 | 2019-12-26 | Danmarks Tekniske Universitet | Solution comprising fluorescent dye as fiducial marker |
| CN110787306A (zh) * | 2018-08-02 | 2020-02-14 | 武汉凯德维斯生物技术有限公司 | 一种用于宫颈癌前哨淋巴结的纳米胶束显像剂的制备与应用 |
| CN109432439A (zh) * | 2018-11-21 | 2019-03-08 | 厦门大学 | 一种具有声动力治疗效果的金属-卟啉纳米颗粒、制备方法及其应用 |
| CN109602921A (zh) * | 2019-01-21 | 2019-04-12 | 深圳市第二人民医院 | 一种锌卟啉纳米晶及其制备方法和应用 |
| CN114073922A (zh) * | 2020-08-20 | 2022-02-22 | 中国科学院苏州纳米技术与纳米仿生研究所 | 卟啉基金属-有机骨架纳米球及其制备方法与应用 |
| WO2022147533A1 (en) * | 2021-01-04 | 2022-07-07 | Nirvana Sciences Inc. | Metallohydroporphyrins for photoacoustic imaging |
Non-Patent Citations (4)
| Title |
|---|
| Light responsive Fe-Tcpp@ICG for hydrogen peroxide detection and inhibition of tumor cell growth;Yu Wang et al.;Biosensors and Bioelectronics;第200卷;第1-8页 * |
| Manganese porphyrin/ICG nanoparticles as magnetic resonance/fluorescent dual-mode probes for imaging of sentinel lymph node metastasis;Xiaomin Fu et al.;J. Mater. Chem. B;第48卷(第10期);第10065–10074页 * |
| Photophysical studies of meso-tetrakis(4-nitrophenyl) and meso- tetrakis(4-sulfophenyl) gallium porphyrins loaded into Pluronic F127 polymeric micelles;Muthumuni Managa et al.;Journal of Photochemistry and Photobiology A: Chemistry;第348卷;第179-187页 * |
| 卟啉纳米技术:探索生物光子学新视角;郑岗;;光学与光电技术(02);第1-5页 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN115501187A (zh) | 2022-12-23 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Hu et al. | Gadolinium-chelated conjugated polymer-based nanotheranostics for photoacoustic/magnetic resonance/NIR-II fluorescence imaging-guided cancer photothermal therapy | |
| Mao et al. | Functional nanoparticles for magnetic resonance imaging | |
| Calvete et al. | Metal coordinated pyrrole-based macrocycles as contrast agents for magnetic resonance imaging technologies: Synthesis and applications | |
| Liang et al. | One-pot synthesis of Gd 3+-functionalized gold nanoclusters for dual model (fluorescence/magnetic resonance) imaging | |
| Xie et al. | PET/NIRF/MRI triple functional iron oxide nanoparticles | |
| Xu et al. | Melanin-manganese nanoparticles with ultrahigh efficient clearance in vivo for tumor-targeting T 1 magnetic resonance imaging contrast agent | |
| Liao et al. | One-pot synthesis of gadolinium (III) doped carbon dots for fluorescence/magnetic resonance bimodal imaging | |
| Wang et al. | Upconverting rare-earth nanoparticles with a paramagnetic lanthanide complex shell for upconversion fluorescent and magnetic resonance dual-modality imaging | |
| Yuzhakova et al. | In vivo multimodal tumor imaging and photodynamic therapy with novel theranostic agents based on the porphyrazine framework-chelated gadolinium (III) cation | |
| CN101444630B (zh) | 一种具有肿瘤靶向功能的高磁共振灵敏度四氧化三铁纳米粒子的制备方法 | |
| Nazari et al. | Current status and future prospects of nanoscale metal–organic frameworks in bioimaging | |
| Deng et al. | Biomedical applications of fluorescent and magnetic resonance imaging dual‐modality probes | |
| Sun et al. | A polyethyleneimine-driven self-assembled nanoplatform for fluorescence and MR dual-mode imaging guided cancer chemotherapy | |
| CN103495186B (zh) | 一种对脑胶质瘤特异靶向的氧化锰纳米粒造影剂 | |
| Du et al. | Improving the MR imaging sensitivity of upconversion nanoparticles by an internal and external incorporation of the Gd3+ strategy for in vivo tumor-targeted imaging | |
| CN115501187B (zh) | 一种金属卟啉基纳米颗粒、制备方法及应用 | |
| Liu et al. | Magnetic nanoparticles modified with DTPA-AMC-rare earth for fluorescent and magnetic resonance dual mode imaging | |
| Chen et al. | Gadolinium–porphyrin based polymer nanotheranostics for fluorescence/magnetic resonance imaging guided photodynamic therapy | |
| Zhang et al. | Chitosan coated gold nanorod chelating gadolinium for MRI-visible photothermal therapy of cancer | |
| Melancon et al. | Development of a macromolecular dual-modality MR-optical imaging for sentinel lymph node mapping | |
| Cui et al. | Gastrin-releasing peptide receptor-targeted gadolinium oxide-based multifunctional nanoparticles for dual magnetic resonance/fluorescent molecular imaging of prostate cancer | |
| Ren et al. | Red emissive carbon dots prepared from polymers as an efficient nanocarrier for coptisine delivery in vivo and in vitro | |
| Dong et al. | Two birds one stone: Facile preparation of AIE-active fluorescent polymeric nanoparticles via self-catalyzed photo-mediated polymerization | |
| Yang et al. | Theranostic nanoparticles with aggregation-induced emission and MRI contrast enhancement characteristics as a dual-modal imaging platform for image-guided tumor photodynamic therapy | |
| Qiu et al. | Liver injury long-term monitoring and fluorescent image-guided tumor surgery using self-assembly amphiphilic donor-acceptor NIR-II dyes |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |