CN113384712A - 一种基于同时杀伤肿瘤细胞和CAFs的共载脂质体及其制备方法 - Google Patents
一种基于同时杀伤肿瘤细胞和CAFs的共载脂质体及其制备方法 Download PDFInfo
- Publication number
- CN113384712A CN113384712A CN202110650300.4A CN202110650300A CN113384712A CN 113384712 A CN113384712 A CN 113384712A CN 202110650300 A CN202110650300 A CN 202110650300A CN 113384712 A CN113384712 A CN 113384712A
- Authority
- CN
- China
- Prior art keywords
- liposome
- drug
- cafs
- tumor cells
- toxic
- 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.)
- Pending
Links
- 239000002502 liposome Substances 0.000 title claims abstract description 115
- 210000004881 tumor cell Anatomy 0.000 title claims abstract description 31
- 230000005909 tumor killing Effects 0.000 title claims abstract description 19
- 238000002360 preparation method Methods 0.000 title abstract description 11
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 claims abstract description 56
- 239000003814 drug Substances 0.000 claims abstract description 50
- 229940079593 drug Drugs 0.000 claims abstract description 36
- -1 cationic lipid Chemical class 0.000 claims abstract description 33
- 231100000331 toxic Toxicity 0.000 claims abstract description 30
- 230000002588 toxic effect Effects 0.000 claims abstract description 30
- 235000012000 cholesterol Nutrition 0.000 claims abstract description 28
- 229940125644 antibody drug Drugs 0.000 claims abstract description 27
- 150000003904 phospholipids Chemical class 0.000 claims abstract description 18
- 229920002521 macromolecule Polymers 0.000 claims abstract description 13
- 150000003384 small molecules Chemical class 0.000 claims abstract description 6
- 125000002091 cationic group Chemical group 0.000 claims abstract description 5
- 150000002605 large molecules Chemical class 0.000 claims abstract description 4
- 125000000129 anionic group Chemical group 0.000 claims abstract description 3
- 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 claims description 26
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 22
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 20
- 229940009456 adriamycin Drugs 0.000 claims description 13
- 239000012528 membrane Substances 0.000 claims description 13
- 238000000034 method Methods 0.000 claims description 13
- 238000001914 filtration Methods 0.000 claims description 11
- KSXTUUUQYQYKCR-LQDDAWAPSA-M 2,3-bis[[(z)-octadec-9-enoyl]oxy]propyl-trimethylazanium;chloride Chemical compound [Cl-].CCCCCCCC\C=C/CCCCCCCC(=O)OCC(C[N+](C)(C)C)OC(=O)CCCCCCC\C=C/CCCCCCCC KSXTUUUQYQYKCR-LQDDAWAPSA-M 0.000 claims description 10
- 238000002156 mixing Methods 0.000 claims description 10
- JLPULHDHAOZNQI-ZTIMHPMXSA-N 1-hexadecanoyl-2-(9Z,12Z-octadecadienoyl)-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCC\C=C/C\C=C/CCCCC JLPULHDHAOZNQI-ZTIMHPMXSA-N 0.000 claims description 9
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 9
- 229930012538 Paclitaxel Natural products 0.000 claims description 9
- UWKQSNNFCGGAFS-XIFFEERXSA-N irinotecan Chemical compound C1=C2C(CC)=C3CN(C(C4=C([C@@](C(=O)OC4)(O)CC)C=4)=O)C=4C3=NC2=CC=C1OC(=O)N(CC1)CCC1N1CCCCC1 UWKQSNNFCGGAFS-XIFFEERXSA-N 0.000 claims description 9
- 229960004768 irinotecan Drugs 0.000 claims description 9
- 229960001592 paclitaxel Drugs 0.000 claims description 9
- 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 claims description 9
- 238000003260 vortexing Methods 0.000 claims description 9
- 229920001223 polyethylene glycol Polymers 0.000 claims description 8
- 239000000243 solution Substances 0.000 claims description 8
- MLDQJTXFUGDVEO-UHFFFAOYSA-N BAY-43-9006 Chemical compound C1=NC(C(=O)NC)=CC(OC=2C=CC(NC(=O)NC=3C=C(C(Cl)=CC=3)C(F)(F)F)=CC=2)=C1 MLDQJTXFUGDVEO-UHFFFAOYSA-N 0.000 claims description 7
- 239000005511 L01XE05 - Sorafenib Substances 0.000 claims description 7
- 229960003787 sorafenib Drugs 0.000 claims description 7
- JQWAHKMIYCERGA-UHFFFAOYSA-N (2-nonanoyloxy-3-octadeca-9,12-dienoyloxypropoxy)-[2-(trimethylazaniumyl)ethyl]phosphinate Chemical compound CCCCCCCCC(=O)OC(COP([O-])(=O)CC[N+](C)(C)C)COC(=O)CCCCCCCC=CCC=CCCCCC JQWAHKMIYCERGA-UHFFFAOYSA-N 0.000 claims description 6
- KILNVBDSWZSGLL-KXQOOQHDSA-N 1,2-dihexadecanoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCCCCCCCCCC KILNVBDSWZSGLL-KXQOOQHDSA-N 0.000 claims description 6
- 229940083466 soybean lecithin Drugs 0.000 claims description 5
- NRJAVPSFFCBXDT-HUESYALOSA-N 1,2-distearoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCCCCCCCCCCCC NRJAVPSFFCBXDT-HUESYALOSA-N 0.000 claims description 4
- 108091008794 FGF receptors Proteins 0.000 claims description 4
- DSNRWDQKZIEDDB-GCMPNPAFSA-N [(2r)-3-[2,3-dihydroxypropoxy(hydroxy)phosphoryl]oxy-2-[(z)-octadec-9-enoyl]oxypropyl] (z)-octadec-9-enoate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OC[C@H](COP(O)(=O)OCC(O)CO)OC(=O)CCCCCCC\C=C/CCCCCCCC DSNRWDQKZIEDDB-GCMPNPAFSA-N 0.000 claims description 4
- 239000006185 dispersion Substances 0.000 claims description 4
- 235000019441 ethanol Nutrition 0.000 claims description 4
- 238000001704 evaporation Methods 0.000 claims description 4
- 238000002347 injection Methods 0.000 claims description 4
- 239000007924 injection Substances 0.000 claims description 4
- 230000002441 reversible effect Effects 0.000 claims description 4
- 230000002194 synthesizing effect Effects 0.000 claims description 4
- 239000007762 w/o emulsion Substances 0.000 claims description 4
- 239000002246 antineoplastic agent Substances 0.000 claims description 3
- 230000000887 hydrating effect Effects 0.000 claims description 3
- 230000003301 hydrolyzing effect Effects 0.000 claims description 3
- 150000002632 lipids Chemical class 0.000 claims description 3
- 239000011259 mixed solution Substances 0.000 claims description 3
- 239000003960 organic solvent Substances 0.000 claims description 3
- 230000008685 targeting Effects 0.000 claims description 3
- 238000002604 ultrasonography Methods 0.000 claims description 3
- 239000002202 Polyethylene glycol Substances 0.000 claims description 2
- 229940044683 chemotherapy drug Drugs 0.000 claims description 2
- 229960004316 cisplatin Drugs 0.000 claims description 2
- DQLATGHUWYMOKM-UHFFFAOYSA-L cisplatin Chemical compound N[Pt](N)(Cl)Cl DQLATGHUWYMOKM-UHFFFAOYSA-L 0.000 claims description 2
- 239000000463 material Substances 0.000 claims description 2
- 229940125645 monoclonal antibody drug Drugs 0.000 claims description 2
- 229940042880 natural phospholipid Drugs 0.000 claims description 2
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 2
- UMSVPCYSAUKCAZ-UHFFFAOYSA-N propane;hydrochloride Chemical compound Cl.CCC UMSVPCYSAUKCAZ-UHFFFAOYSA-N 0.000 claims description 2
- 239000002994 raw material Substances 0.000 claims description 2
- 101000692455 Homo sapiens Platelet-derived growth factor receptor beta Proteins 0.000 claims 1
- 102100026547 Platelet-derived growth factor receptor beta Human genes 0.000 claims 1
- 102000052178 fibroblast growth factor receptor activity proteins Human genes 0.000 claims 1
- 239000008347 soybean phospholipid Substances 0.000 claims 1
- 206010028980 Neoplasm Diseases 0.000 abstract description 24
- 210000002950 fibroblast Anatomy 0.000 abstract description 5
- 230000000694 effects Effects 0.000 abstract description 4
- 238000001179 sorption measurement Methods 0.000 abstract description 4
- 206010009944 Colon cancer Diseases 0.000 abstract description 3
- 208000001333 Colorectal Neoplasms Diseases 0.000 abstract description 3
- 231100000433 cytotoxic Toxicity 0.000 abstract 1
- 230000001472 cytotoxic effect Effects 0.000 abstract 1
- 238000011068 loading method Methods 0.000 description 14
- 239000002245 particle Substances 0.000 description 11
- 206010027476 Metastases Diseases 0.000 description 7
- 230000009401 metastasis Effects 0.000 description 7
- ZAHRKKWIAAJSAO-UHFFFAOYSA-N rapamycin Natural products COCC(O)C(=C/C(C)C(=O)CC(OC(=O)C1CCCCN1C(=O)C(=O)C2(O)OC(CC(OC)C(=CC=CC=CC(C)CC(C)C(=O)C)C)CCC2C)C(C)CC3CCC(O)C(C3)OC)C ZAHRKKWIAAJSAO-UHFFFAOYSA-N 0.000 description 7
- QFJCIRLUMZQUOT-HPLJOQBZSA-N sirolimus Chemical compound C1C[C@@H](O)[C@H](OC)C[C@@H]1C[C@@H](C)[C@H]1OC(=O)[C@@H]2CCCCN2C(=O)C(=O)[C@](O)(O2)[C@H](C)CC[C@H]2C[C@H](OC)/C(C)=C/C=C/C=C/[C@@H](C)C[C@@H](C)C(=O)[C@H](OC)[C@H](O)/C(C)=C/[C@@H](C)C(=O)C1 QFJCIRLUMZQUOT-HPLJOQBZSA-N 0.000 description 7
- 229960002930 sirolimus Drugs 0.000 description 7
- 238000001514 detection method Methods 0.000 description 5
- 230000000052 comparative effect Effects 0.000 description 4
- 238000009826 distribution Methods 0.000 description 4
- IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 description 3
- 102000044168 Fibroblast Growth Factor Receptor Human genes 0.000 description 3
- 108091008606 PDGF receptors Proteins 0.000 description 3
- 102000011653 Platelet-Derived Growth Factor Receptors Human genes 0.000 description 3
- 238000002512 chemotherapy Methods 0.000 description 3
- 210000002969 egg yolk Anatomy 0.000 description 3
- 229940067606 lecithin Drugs 0.000 description 3
- 235000010445 lecithin Nutrition 0.000 description 3
- 239000000787 lecithin Substances 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- 238000003917 TEM image Methods 0.000 description 2
- 206010064390 Tumour invasion Diseases 0.000 description 2
- 201000011510 cancer Diseases 0.000 description 2
- 230000009400 cancer invasion Effects 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 102000005962 receptors Human genes 0.000 description 2
- 108020003175 receptors Proteins 0.000 description 2
- 239000002689 soil Substances 0.000 description 2
- 238000003860 storage Methods 0.000 description 2
- 210000002536 stromal cell Anatomy 0.000 description 2
- 230000002195 synergetic effect Effects 0.000 description 2
- 238000002560 therapeutic procedure Methods 0.000 description 2
- 102000007469 Actins Human genes 0.000 description 1
- 108010085238 Actins Proteins 0.000 description 1
- 206010061309 Neoplasm progression Diseases 0.000 description 1
- 102000007460 S100 Calcium-Binding Protein A4 Human genes 0.000 description 1
- 108010085149 S100 Calcium-Binding Protein A4 Proteins 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 238000007792 addition Methods 0.000 description 1
- 229940041181 antineoplastic drug Drugs 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 210000004204 blood vessel Anatomy 0.000 description 1
- 210000004027 cell Anatomy 0.000 description 1
- 230000004663 cell proliferation Effects 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 238000011960 computer-aided design Methods 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 238000012377 drug delivery Methods 0.000 description 1
- 238000002651 drug therapy Methods 0.000 description 1
- 238000005538 encapsulation Methods 0.000 description 1
- 230000007705 epithelial mesenchymal transition Effects 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 229940099578 hydrogenated soybean lecithin Drugs 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 230000009545 invasion Effects 0.000 description 1
- 230000002147 killing effect Effects 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 231100000053 low toxicity Toxicity 0.000 description 1
- 210000002540 macrophage Anatomy 0.000 description 1
- 230000036210 malignancy Effects 0.000 description 1
- 230000006609 metabolic stress Effects 0.000 description 1
- 210000003205 muscle Anatomy 0.000 description 1
- 210000004985 myeloid-derived suppressor cell Anatomy 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 238000009210 therapy by ultrasound Methods 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 230000005747 tumor angiogenesis Effects 0.000 description 1
- 230000005751 tumor progression Effects 0.000 description 1
- 230000003313 weakening effect Effects 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
- A61K47/69—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 conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit
- A61K47/6905—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 conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit the form being a colloid or an emulsion
- A61K47/6911—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 conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit the form being a colloid or an emulsion the form being a liposome
- A61K47/6913—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 conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit the form being a colloid or an emulsion the form being a liposome the liposome being modified on its surface by an antibody
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/337—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having four-membered rings, e.g. taxol
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
- A61K31/4738—Quinolines; Isoquinolines ortho- or peri-condensed with heterocyclic ring systems
- A61K31/4745—Quinolines; Isoquinolines ortho- or peri-condensed with heterocyclic ring systems condensed with ring systems having nitrogen as a ring hetero atom, e.g. phenantrolines
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7028—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages
- A61K31/7034—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin
- A61K31/704—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin attached to a condensed carbocyclic ring system, e.g. sennosides, thiocolchicosides, escin, daunorubicin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K33/00—Medicinal preparations containing inorganic active ingredients
- A61K33/24—Heavy metals; Compounds thereof
- A61K33/243—Platinum; Compounds thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
- A61K39/39533—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals
- A61K39/3955—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals against proteinaceous materials, e.g. enzymes, hormones, lymphokines
-
- 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
- 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
- A61K47/68—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 antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
- A61K47/6835—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 antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment the modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site
- A61K47/6849—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 antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment the modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site the antibody targeting a receptor, a cell surface antigen or a cell surface determinant
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Epidemiology (AREA)
- Immunology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Organic Chemistry (AREA)
- Cell Biology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Inorganic Chemistry (AREA)
- Molecular Biology (AREA)
- Endocrinology (AREA)
- Microbiology (AREA)
- Mycology (AREA)
- Dispersion Chemistry (AREA)
- Medicinal Preparation (AREA)
Abstract
本发明公开了一种基于同时杀伤肿瘤细胞和CAFs的共载脂质体及其制备方法,属于脂质体药剂技术领域,所述共载脂质体为共载小分子毒性药物和大分子抗体药物的脂质体,包括以下组分:磷脂、胆固醇、小分子毒性药物和大分子抗体药物,所述磷脂由阴离子脂质和阳离子脂质组成。所述小分子毒性药物与磷脂的质量比为1:5‑1:100,所述阳离子脂质与磷脂的摩尔比为0.05:1‑0.5:1,所述阴离子脂质与胆固醇的质量比为19:5,所述大分子抗体药物与阳离子脂质的质量比为1:45‑1:900。可实现大分子抗体药物特异性吸附及响应性脱落,能够同时杀伤肿瘤细胞以及肿瘤相关成纤维细胞(CAFs),提高结直肠癌的治疗效果。
Description
技术领域
本发明涉及脂质体药剂技术领域,具体涉及一种基于同时杀伤肿瘤细胞和CAFs的共载脂质体及其制备方法。
背景技术
癌症作为最常见的恶性肿瘤之一,具有较高的发病率和死亡率。化学治疗作为目前临床上抗肿瘤药物治疗的主要手段,可直接杀伤肿瘤细胞,从而抑制肿瘤的生长增殖。然而,单一化学治疗很难彻底清除肿瘤细胞,很容易引起肿瘤转移及复发,造成肿瘤治疗失败和患者死亡。目前肿瘤治疗的最大障碍仍在于肿瘤的转移和复发。
肿瘤微环境是肿瘤细胞赖以生存的场所,除肿瘤细胞外,还存在着大量的基质细胞如:肿瘤相关成纤维细胞、肿瘤相关巨噬细胞、髓源性抑制细胞等,为肿瘤的侵袭转移等提供了必要的“土壤”。肿瘤治疗必须综合考虑肿瘤微环境中肿瘤细胞与其他成分之间的密切联系,方有望取得肿瘤治疗的成功。因此,在化学治疗杀伤肿瘤细胞的基础上,如何进一步阻断肿瘤细胞生存的“土壤”,从而重塑肿瘤微环境,有效降低肿瘤转移和复发,是肿瘤研究领域亟待解决的重要科学问题。
肿瘤相关成纤维细胞(CAFs)是肿瘤微环境中最主要的组成部分,可促进上皮-间质转化、参与肿瘤血管生成、继发活性氧诱导的代谢应激反应,从而促进肿瘤的侵袭和转移。减少CAFs产生,可破坏肿瘤微环境的完整性,削弱肿瘤侵袭转移能力,延缓肿瘤进展。CAFs是基质细胞最主要成分之一,其表面高表达受体如成纤维细胞激活蛋白(FAP),α-平滑肌肌动蛋白(α-SMA),成纤维细胞特异性蛋白1(FSP-1),血小板衍生生长因子受体(PDGFR),成纤维细胞生长因子受体(FGFR),可作为结直肠癌治疗的有效靶标。
脂质体作为一种优良的药物递送载体,具有靶向、易于修饰和低毒等优点,表现出极高的应用前景和市场转化潜力。因此,设计脂质体以期实现小分子毒性药物与大分子抗体药物共载及共递送至肿瘤部位,并将二者分别释放并特异性靶向至各自靶点发挥协同治疗作用至关重要。
发明内容
针对上述技术问题,本发明提供一种基于同时杀伤肿瘤细胞和CAFs的共载脂质体及其制备方法,可实现大分子抗体药物特异性吸附及响应性脱落,能够同时杀伤肿瘤细胞以及肿瘤相关成纤维细胞(CAFs),提高结直肠癌的治疗效果。
为了实现上述目的,本发明采用的技术方案如下:
一种基于同时杀伤肿瘤细胞和CAFs的共载脂质体,所述共载脂质体为共载小分子毒性药物和大分子抗体药物的脂质体,包括以下组分:磷脂、胆固醇、小分子毒性药物和大分子抗体药物,所述磷脂由阴离子脂质和阳离子脂质组成。
优选的,所述小分子毒性药物与磷脂的质量比为1:5-1:100,所述阳离子脂质与磷脂的摩尔比为0.05:1-0.5:1,所述阴离子脂质与胆固醇的质量比为19:5,所述大分子抗体药物与阳离子脂质的质量比为1:45-1:900。
优选的,所述阴离子脂质可选用天然磷脂,如大豆卵磷脂、蛋黄卵磷脂、氢化大豆磷脂中的任意一种或多种,也可选用合成磷脂,如二棕榈酰磷脂酰胆碱(DPPC)、二油酰磷脂酰甘油(DOPG)、二硬脂酰磷脂酰胆碱(DSPC)中的任意一种或多种;所述阳离子脂质可选用1,2-双十八烯氧基-3-甲基铵丙烷氯盐(DOTMA)、(2,3-二油酰基-丙基)-三甲基氯化铵(DOTAP)中的任意一种,也可选用通过阳离子短肽与聚乙二醇化磷脂DSPE-PEG合成得到的正电性材料,如九聚精氨酸(R9)与DSPE-PEG合成得到DSPE-PEG-R9。
优选的,所述小分子毒性药物为作用于肿瘤细胞的化学治疗药物,如顺铂、伊立替康、阿霉素、索拉非尼、紫杉醇中的任意一种。
优选的,所述大分子抗体药物为作用于CAFs的药物,如单克隆抗体药物(mAb)、单链单抗(scFv)中的任意一种,其靶向CAFs的靶点可以是FAP,α-SMA,FSP-1,PDGFR,FGFR中的任意一个靶点。
本发明还提供一种基于同时杀伤肿瘤细胞和CAFs的共载脂质体的制备方法,包括以下步骤:
(1)以磷脂、胆固醇以及小分子毒性药物为原料,制得单载小分子毒性药物的正电性脂质体;
(2)大分子抗体药物通过静电作用力吸附于上述正电性脂质体的表面,制得共载小分子毒性药物和大分子抗体药物的脂质体。
优选的,所述步骤(1)中,可通过乙醇注入法、逆向蒸发法、薄膜分散法中的任意一种方法得到正电性脂质体。
进一步优选的,所述乙醇注入法的具体步骤为:
将阴离子脂质、阳离子脂质、胆固醇以及小分子毒性药物溶解于无水乙醇中,在转速20rpm/分,温度为60℃条件下注入一定体积的PBS中,1h后得到正电性脂质体;
所述逆向蒸发法的具体步骤为:
将阴离子脂质、阳离子脂质、胆固醇以及小分子毒性药物溶解于氯仿中,并加入少量PBS溶液,短时超声至形成油包水型乳浊液,使用旋转蒸发仪抽真空除去氯仿至形成凝胶,然后补加适量PBS至指定体积,在60℃下水化1h得到正电性脂质体;
所述薄膜分散法的具体步骤为:
将阴离子脂质、阳离子脂质、胆固醇以及小分子毒性药物溶解于氯仿/甲醇混合液中,使用旋转蒸发仪抽真空除去有机溶剂得到均匀脂质薄膜,加入一定体积的PBS溶液于60℃下水化1h得到正电性脂质体。
优选的,所述步骤(2)的具体步骤为:将大分子抗体药物与上述正电性脂质体混合涡旋15min,过450nm、200nm滤膜各3次,即得到共载小分子毒性药物和大分子抗体药物的脂质体。
本发明的有益效果表现在:
本发明小分子毒性药物需具有一定的疏水性,通过物理包封形式包载于脂质体内部,大分子抗体药物呈电负性,与阳离子脂质通过静电吸附连接于脂质体表面,由于受体与配体的结合作用力大于大分子抗体药物与阳离子脂质的静电吸引力,从而实现大分子抗体药物在与CAFs结合后,从脂质体响应性脱落。本发明的共载脂质体可充分发挥小分子毒性药物与大分子抗体药物的协同治疗作用,能够同时杀伤肿瘤细胞和CAFs,抑制细胞增殖和转移,提高癌症治疗效果。
附图说明
图1为本发明实施例1制备的共载脂质体的透射电镜照片。
图2为本发明实施例1制备的共载脂质体的粒径分布图。
图3为本发明实施例1制备的共载脂质体的电位分布图。
图4为本发明实施例1制备的共载脂质体在贮存14天期间的粒径和PDI变化图。
具体实施方式
为了便于本领域技术人员理解,下面结合附图对本发明作进一步的说明。
实施例1
一种基于同时杀伤肿瘤细胞和CAFs的共载脂质体,所述共载脂质体为共载伊立替康/anti-FAP scFv脂质体,由以下组分制备而成:蛋黄卵磷脂95mg、胆固醇25mg、DSPE-PEG-R927mg、伊立替康15mg、anti-FAP scFv(单链单抗中的一种,其与DSPE-PEG-R9质量比为1:540)。
上述共载脂质体的制备方法,包括以下步骤:首先将称量好的蛋黄卵磷脂、胆固醇、DSPE-PEG-R9、伊立替康,溶解于2mL无水乙醇中,在转速20rpm/分,温度为60℃条件下注入5mL PBS中,1h后得到正电性脂质体;然后将anti-FAP scFv与上述正电性脂质体混合涡旋15min,过450nm、200nm滤膜各3次,得到共载伊立替康/anti-FAP scFv的脂质体。
经检测,共载脂质体中伊立替康的浓度为2.8mg/mL,包封率93%,载药量9.3%。
如图1所示为共载脂质体的透射电镜照片,如图2所示为共载脂质体的粒径分布图,测得共载脂质体的平均粒径为125nm。
如图3所示为共载脂质体的电位分布图,显示共载脂质体的电位为-3.7mV,电负性有利于脂质体在静脉给药后与血管或细胞表面电负性物质相排斥而保持稳定。
如图4所示为共载脂质体的贮存14天期间的粒径和PDI变化图,结果显示该脂质体初步稳定性良好。
实施例2
一种基于同时杀伤肿瘤细胞和CAFs的共载脂质体,所述共载脂质体为共载阿霉素/anti-FAP scFv脂质体,由以下组分制备而成:大豆卵磷脂95mg、胆固醇25mg、DSPE-PEG-R927mg、阿霉素5mg、anti-FAP scFv(单链单抗中的一种,其与DSPE-PEG-R9质量比为1:270)。
上述共载脂质体的制备方法,包括以下步骤:首先将称量好的大豆卵磷脂、胆固醇、DSPE-PEG-R9、阿霉素,溶解于6mL氯仿中,并加入2mL PBS溶液,短时超声至形成油包水型乳浊液,使用旋转蒸发仪抽真空除去氯仿至形成凝胶,然后补加适量PBS至5mL,在60℃下水化1h后得到正电性脂质体;然后将anti-FAP scFv与上述正电性脂质体混合涡旋15min,过450nm、200nm滤膜各3次,得到共载阿霉素/anti-FAP scFv的脂质体。
经检测,共载脂质体中阿霉素的浓度为0.88mg/mL,包封率88%,载药量2.9%。共载脂质体的平均粒径为118nm。
实施例3
一种基于同时杀伤肿瘤细胞和CAFs的共载脂质体,所述共载脂质体为共载索拉非尼/西罗珠单抗脂质体,由以下组分制备而成:氢化大豆磷脂95mg、胆固醇25mg、DOTAP4.5mg、索拉非尼15mg、西罗珠单抗(单克隆抗体药物中的一种,其与DOTAP质量比为1:540)。
上述共载脂质体的制备方法,包括以下步骤:首先将称量好的氢化大豆磷脂、胆固醇、DOTAP、索拉非尼,溶解于4mL氯仿/甲醇混合液中,使用旋转蒸发仪抽真空除去有机溶剂得到均匀脂质薄膜,后加入5mL PBS溶液于60℃下水化1h后得到正电性脂质体;然后将西罗珠单抗与上述正电性脂质体混合涡旋15min,过450nm、200nm滤膜各3次,得到共载索拉非尼/西罗珠单抗的脂质体。
经检测,共载脂质体中索拉菲尼的浓度为1.6mg/mL,包封率80%,载药量6%。共载脂质体的平均粒径为115nm。
实施例4
一种基于同时杀伤肿瘤细胞和CAFs的共载脂质体,所述共载脂质体为共载阿霉素/西罗珠单抗脂质体,由以下组分制备而成:DPPC 95mg、胆固醇25mg、DOTAP 16mg、阿霉素8mg、西罗珠单抗(单克隆抗体药物中的一种,其与DOTAP质量比为1:400)。
上述共载脂质体的制备方法,包括以下步骤:首先将称量好的DPPC、胆固醇、DOTAP、阿霉素,溶解于2mL无水乙醇中,在转速20rpm/分,温度为60℃条件下注入5mL PBS中,1h后得到正电性脂质体;然后将西罗珠单抗与上述正电性脂质体混合涡旋15min,过450nm、200nm滤膜各3次,得到共载阿霉素/西罗珠单抗的脂质体。
经检测,共载脂质体中阿霉素的浓度为1.12mg/mL,包封率70%,载药量3.9%。共载脂质体的平均粒径为138nm。
实施例5
一种基于同时杀伤肿瘤细胞和CAFs的共载脂质体,所述共载脂质体为共载紫杉醇/贝马里妥珠单抗脂质体,由以下组分制备而成:蛋黄卵磷脂95mg、胆固醇25mg、DOTMA27mg、紫杉醇10mg、贝马里妥珠单抗(单克隆抗体药物中的一种,其与DOTMA质量比为1:200)。
上述共载脂质体的制备方法,包括以下步骤:首先将称量好的蛋黄卵磷脂、胆固醇、DOTMA、紫杉醇,溶解于2mL无水乙醇中,在转速20rpm/分,温度为60℃条件下注入5mLPBS中,1h后得到正电性脂质体;然后将贝马里妥珠单抗与上述正电性脂质体混合涡旋15min,过450nm、200nm滤膜各3次,得到共载紫杉醇/贝马里妥珠单抗的脂质体。
经检测,共载脂质体中紫杉醇的浓度为1.8mg/mL,包封率90%,载药量5.8%。共载脂质体的平均粒径为135nm。
对比例1
取大豆卵磷脂95mg、胆固醇25mg、DSPE-PEG-R9 27 mg、伊立替康10mg,anti-FAPscFv0.01g,溶解于2mL无水乙醇中,在转速在20rpm/分,温度为60℃条件下注入5mL PBS中,1h后得到脂质体,过450nm、200nm滤膜各3次,得到最终脂质体。
该方法无法实现两药共载,可见,小分子毒性药物和大分子抗体药物的加入顺序对本发明中的共载脂质体的的包封率和载药量有重要影响。
对比例2
取蛋黄卵磷脂100mg、胆固醇25mg、阿霉素10mg,溶解于6mL氯仿中,并加入2mL PBS溶液,短时超声至形成油包水型乳浊液,使用旋转蒸发仪抽真空除去氯仿至形成凝胶,然后补加适量PBS至5mL,在60℃下水化1h得到载紫杉醇脂质体。随后将西罗珠单抗0.4mg与脂质体混合涡旋15min,过450nm、200nm滤膜各3次,得到脂质体。
该方法无法实现西罗珠单抗的负载,可见,阳离子脂质是单抗吸附连接的必要条件。
对比例3
取蛋黄卵磷脂85mg、胆固醇25mg、DSPE-PEG-R981 mg、紫杉醇10mg,溶解于2mL无水乙醇中,在转速在20rpm/分,温度为60℃条件下注入5mL PBS中,1h后得到正电性脂质体,然后将西罗珠单抗(与DSPE-PEG-R9质量比为1:25)与上述正电性脂质体混合涡旋15min,过450nm后,过220nm滤膜失败。
该方法加入阳离子脂质的比例过高,且加入大分子抗体药物的比例高,得到共载脂质体的粒径较大,粒径分布不均匀,无法保证共载脂质体的稳定性。
对比例4
取蛋黄卵磷脂95mg、胆固醇25mg、DOTAP 27mg、伊立替康10mg,溶解于2mL无水乙醇中,在转速在20rpm/分,温度为60℃条件下注入5mL PBS中,1h后得到正电性脂质体,将anti-FAP scFv(与DOTAP质量比为1:2700)与上述正电性脂质体混合涡旋15min,过450nm、200nm滤膜各3次,得到共载小分子毒性药物/大分子抗体药物脂质体。
得到的共载脂质体的zeta电位为5.76mV,呈正电性,可见,大分子抗体药物加入的比例是屏蔽阳离子脂质正电性的关键。
以上内容仅仅是对本发明的结构所作的举例和说明,所属本技术领域的技术人员对所描述的具体实施例做各种各样的修改或补充或采用类似的方式替代,只要不偏离发明的结构或者超越本权利要求书所定义的范围,均应属于本发明的保护范围。
Claims (9)
1.一种基于同时杀伤肿瘤细胞和CAFs的共载脂质体,其特征在于,所述共载脂质体为共载小分子毒性药物和大分子抗体药物的脂质体,包括以下组分:磷脂、胆固醇、小分子毒性药物和大分子抗体药物,所述磷脂由阴离子脂质和阳离子脂质组成。
2.根据权利要求1所述的一种基于同时杀伤肿瘤细胞和CAFs的共载脂质体,其特征在于,所述小分子毒性药物与磷脂的质量比为1:5-1:100,所述阳离子脂质与磷脂的摩尔比为0.05:1-0.5:1,所述阴离子脂质与胆固醇的质量比为19:5,所述大分子抗体药物与阳离子脂质的质量比为1:45-1:900。
3.根据权利要求2所述的一种基于同时杀伤肿瘤细胞和CAFs的共载脂质体,其特征在于,所述阴离子脂质可选用天然磷脂,如大豆卵磷脂、蛋黄卵磷脂、氢化大豆磷脂中的任意一种或多种,也可选用合成磷脂,如二棕榈酰磷脂酰胆碱(DPPC)、二油酰磷脂酰甘油(DOPG)、二硬脂酰磷脂酰胆碱(DSPC)中的任意一种或多种;所述阳离子脂质可选用1,2-双十八烯氧基-3-甲基铵丙烷氯盐(DOTMA)、(2,3-二油酰基-丙基)-三甲基氯化铵(DOTAP)中的任意一种,也可选用通过阳离子短肽与聚乙二醇化磷脂DSPE-PEG合成得到的正电性材料,如九聚精氨酸(R9)与DSPE-PEG合成得到DSPE-PEG-R9。
4.根据权利要求2所述的一种基于同时杀伤肿瘤细胞和CAFs的共载脂质体,其特征在于,所述小分子毒性药物为作用于肿瘤细胞的化学治疗药物,如顺铂、伊立替康、阿霉素、索拉非尼、紫杉醇中的任意一种。
5.根据权利要求2所述的一种基于同时杀伤肿瘤细胞和CAFs的共载脂质体,其特征在于,所述大分子抗体药物为作用于CAFs的药物,如单克隆抗体药物(mAb)、单链单抗(scFv)中的任意一种,其靶向CAFs的靶点可以是FAP,α-SMA,FSP-1,PDGFR,FGFR中的任意一个靶点。
6.权利要求1-5任意一项所述的一种基于同时杀伤肿瘤细胞和CAFs的共载脂质体的制备方法,其特征在于,包括以下步骤:
(1)以磷脂、胆固醇以及小分子毒性药物为原料,制得单载小分子毒性药物的正电性脂质体;
(2)大分子抗体药物通过静电作用力吸附于上述正电性脂质体的表面,制得共载小分子毒性药物和大分子抗体药物的脂质体。
7.根据权利要求6所述的一种基于同时杀伤肿瘤细胞和CAFs的共载脂质体的制备方法,其特征在于,所述步骤(1)中,可通过乙醇注入法、逆向蒸发法、薄膜分散法中的任意一种方法得到正电性脂质体。
8.根据权利要求7所述的一种基于同时杀伤肿瘤细胞和CAFs的共载脂质体的制备方法,其特征在于,所述乙醇注入法的具体步骤为:
将阴离子脂质、阳离子脂质、胆固醇以及小分子毒性药物溶解于无水乙醇中,在转速20rpm/分,温度为60℃条件下注入一定体积的PBS中,1h后得到正电性脂质体;
所述逆向蒸发法的具体步骤为:
将阴离子脂质、阳离子脂质、胆固醇以及小分子毒性药物溶解于氯仿中,并加入少量PBS溶液,短时超声至形成油包水型乳浊液,使用旋转蒸发仪抽真空除去氯仿至形成凝胶,然后补加适量PBS至指定体积,在60℃下水化1h得到正电性脂质体;
所述薄膜分散法的具体步骤为:
将阴离子脂质、阳离子脂质、胆固醇以及小分子毒性药物溶解于氯仿/甲醇混合液中,使用旋转蒸发仪抽真空除去有机溶剂得到均匀脂质薄膜,加入一定体积的PBS溶液于60℃下水化1h得到正电性脂质体。
9.根据权利要求6所述的一种基于同时杀伤肿瘤细胞和CAFs的共载脂质体的制备方法,其特征在于,所述步骤(2)的具体步骤为:将大分子抗体药物与上述正电性脂质体混合涡旋15min,过450nm、200nm滤膜各3次,即得到共载小分子毒性药物和大分子抗体药物的脂质体。
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202110650300.4A CN113384712A (zh) | 2021-06-11 | 2021-06-11 | 一种基于同时杀伤肿瘤细胞和CAFs的共载脂质体及其制备方法 |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202110650300.4A CN113384712A (zh) | 2021-06-11 | 2021-06-11 | 一种基于同时杀伤肿瘤细胞和CAFs的共载脂质体及其制备方法 |
Publications (1)
Publication Number | Publication Date |
---|---|
CN113384712A true CN113384712A (zh) | 2021-09-14 |
Family
ID=77620417
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN202110650300.4A Pending CN113384712A (zh) | 2021-06-11 | 2021-06-11 | 一种基于同时杀伤肿瘤细胞和CAFs的共载脂质体及其制备方法 |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN113384712A (zh) |
Cited By (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN114652819A (zh) * | 2022-03-21 | 2022-06-24 | 滨州医学院 | 一种靶向肿瘤微环境可降解的多功能纳米材料及其制备方法 |
CN114652820A (zh) * | 2022-03-22 | 2022-06-24 | 中国药科大学 | 一种阳离子脂质体纳米粒及其制备方法和应用 |
CN117281774A (zh) * | 2023-11-24 | 2023-12-26 | 潍坊医学院 | 基于抑制肿瘤cox-2和cxcr4的共载脂质纳米胶束及制备方法 |
Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2002078608A2 (en) * | 2001-04-02 | 2002-10-10 | Georgetown University | A simplified and improved method for preparing an antibody or an antibody fragment targeted immunoliposome or polyplex for systemic administration of a therapeutic or diagnostic agent |
CN101361712A (zh) * | 2008-09-28 | 2009-02-11 | 四川大学 | 成纤维生长因子受体介导的血管靶向脂质体载体及制备方法和用途 |
CN101484139A (zh) * | 2006-05-15 | 2009-07-15 | 乔治敦大学 | 用于治疗剂或诊断剂的全身施用的抗体或抗体片段靶向的免疫脂质体的制备及其应用 |
CN112076158A (zh) * | 2020-08-28 | 2020-12-15 | 西南民族大学 | 一种治疗慢性肾炎的脂质体-纳米粒复合体 |
-
2021
- 2021-06-11 CN CN202110650300.4A patent/CN113384712A/zh active Pending
Patent Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2002078608A2 (en) * | 2001-04-02 | 2002-10-10 | Georgetown University | A simplified and improved method for preparing an antibody or an antibody fragment targeted immunoliposome or polyplex for systemic administration of a therapeutic or diagnostic agent |
CN101484139A (zh) * | 2006-05-15 | 2009-07-15 | 乔治敦大学 | 用于治疗剂或诊断剂的全身施用的抗体或抗体片段靶向的免疫脂质体的制备及其应用 |
CN101361712A (zh) * | 2008-09-28 | 2009-02-11 | 四川大学 | 成纤维生长因子受体介导的血管靶向脂质体载体及制备方法和用途 |
CN112076158A (zh) * | 2020-08-28 | 2020-12-15 | 西南民族大学 | 一种治疗慢性肾炎的脂质体-纳米粒复合体 |
Non-Patent Citations (2)
Title |
---|
TIANJIAO JI ET AL.: "Peptide Assembly Integration of Fibroblast-Targeting and Cell-Penetration Features for Enhanced Antitumor Drug Delivery", 《ADVANCED MATERIALS》 * |
龚守良, 北京:中国医药科技出版社 * |
Cited By (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN114652819A (zh) * | 2022-03-21 | 2022-06-24 | 滨州医学院 | 一种靶向肿瘤微环境可降解的多功能纳米材料及其制备方法 |
CN114652820A (zh) * | 2022-03-22 | 2022-06-24 | 中国药科大学 | 一种阳离子脂质体纳米粒及其制备方法和应用 |
CN114652820B (zh) * | 2022-03-22 | 2024-02-06 | 中国药科大学 | 一种阳离子脂质体纳米粒及其制备方法和应用 |
CN117281774A (zh) * | 2023-11-24 | 2023-12-26 | 潍坊医学院 | 基于抑制肿瘤cox-2和cxcr4的共载脂质纳米胶束及制备方法 |
CN117281774B (zh) * | 2023-11-24 | 2024-02-09 | 潍坊医学院 | 基于抑制肿瘤cox-2和cxcr4的共载脂质纳米胶束及制备方法 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
TWI362931B (en) | Irinotecan formulation | |
US3993754A (en) | Liposome-encapsulated actinomycin for cancer chemotherapy | |
US6461637B1 (en) | Method of administering liposomal encapsulated taxane | |
US6146659A (en) | Method of administering liposomal encapsulated taxane | |
US9532949B2 (en) | Intraperitoneally-administered nanocarriers that release their therapeutic load based on the inflammatory environment of cancers | |
US9814734B2 (en) | Bufalin liposome, preparation method therefor and application thereof | |
JP2006513984A (ja) | 医薬的に活性な、脂質をベースにしたsn38製剤 | |
JPH08508046A (ja) | タキソール製剤 | |
CN113384712A (zh) | 一种基于同时杀伤肿瘤细胞和CAFs的共载脂质体及其制备方法 | |
US9302003B2 (en) | Compositions comprising a radiosensitizer and an anti-cancer agent and methods of uses thereof | |
CN101933904B (zh) | 一种长春瑞滨长循环脂质体制剂及其制备方法 | |
CN103735509A (zh) | 一种米铂脂质体及其制备方法 | |
CN103622912A (zh) | 盐酸多柔比星-多西他赛或紫杉醇脂质体制剂及其制备方法 | |
JP6230538B2 (ja) | 安定なオキサリプラチン封入リポソーム水分散液及びその安定化方法 | |
JP7057434B2 (ja) | 薬物を内包するリポソーム組成物およびプラチナ製剤を含む組合せ医薬 | |
KR20150047336A (ko) | 나노입자, 이를 제조하는 방법, 및 이의 용도 | |
CN101849915A (zh) | 异长春花碱隐形脂质体冻干粉针剂及其制备方法 | |
CN113750241A (zh) | 一种包载光热剂和化疗药物含钙微沉淀脂质体及其制备方法和应用 | |
Jing-Jing et al. | Fabrication of a folic acid-modified arsenic trioxide prodrug liposome and assessment of its anti-hepatocellular carcinoma activity | |
CN116648252A (zh) | 微脂体组合物及其制备方法 | |
CN103040764B (zh) | 一种盐酸平阳霉素脂质体注射剂 | |
CA2792953A1 (en) | Compositions comprising a radiosensitizer and an anti-cancer agent and methods of uses thereof | |
US7314637B1 (en) | Method of administering liposomal encapsulated taxane | |
US10925831B2 (en) | Liposomal formulations of platinum-acridine anticancer agents and methods thereof | |
Maurya | LIPOSOMES USED AS NOVEL TARGETED |
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 | ||
RJ01 | Rejection of invention patent application after publication |
Application publication date: 20210914 |
|
RJ01 | Rejection of invention patent application after publication |