CN118079023A - 一种在肿瘤微环境实现原位自组装的多功能纳米材料及其制备方法与应用 - Google Patents
一种在肿瘤微环境实现原位自组装的多功能纳米材料及其制备方法与应用 Download PDFInfo
- Publication number
- CN118079023A CN118079023A CN202310983615.XA CN202310983615A CN118079023A CN 118079023 A CN118079023 A CN 118079023A CN 202310983615 A CN202310983615 A CN 202310983615A CN 118079023 A CN118079023 A CN 118079023A
- Authority
- CN
- China
- Prior art keywords
- fept
- nano alloy
- assembly
- tumor microenvironment
- realizing
- 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
- 206010028980 Neoplasm Diseases 0.000 title claims abstract description 46
- 239000002086 nanomaterial Substances 0.000 title claims abstract description 20
- 238000011065 in-situ storage Methods 0.000 title claims abstract description 17
- 238000002360 preparation method Methods 0.000 title claims abstract description 17
- 238000001338 self-assembly Methods 0.000 title claims abstract description 17
- 229910005335 FePt Inorganic materials 0.000 claims abstract description 68
- 239000000956 alloy Substances 0.000 claims abstract description 61
- 229910045601 alloy Inorganic materials 0.000 claims abstract description 61
- 238000006243 chemical reaction Methods 0.000 claims abstract description 17
- 238000000034 method Methods 0.000 claims abstract description 15
- ACTRVOBWPAIOHC-XIXRPRMCSA-N succimer Chemical compound OC(=O)[C@@H](S)[C@@H](S)C(O)=O ACTRVOBWPAIOHC-XIXRPRMCSA-N 0.000 claims abstract description 8
- 239000003814 drug Substances 0.000 claims abstract description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 32
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 21
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 21
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 19
- 239000000243 solution Substances 0.000 claims description 18
- 238000005406 washing Methods 0.000 claims description 18
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 15
- MHDVGSVTJDSBDK-UHFFFAOYSA-N dibenzyl ether Chemical compound C=1C=CC=CC=1COCC1=CC=CC=C1 MHDVGSVTJDSBDK-UHFFFAOYSA-N 0.000 claims description 14
- 239000012153 distilled water Substances 0.000 claims description 14
- 230000015572 biosynthetic process Effects 0.000 claims description 12
- 238000003786 synthesis reaction Methods 0.000 claims description 12
- WRIDQFICGBMAFQ-UHFFFAOYSA-N (E)-8-Octadecenoic acid Natural products CCCCCCCCCC=CCCCCCCC(O)=O WRIDQFICGBMAFQ-UHFFFAOYSA-N 0.000 claims description 11
- QGLWBTPVKHMVHM-KTKRTIGZSA-N (z)-octadec-9-en-1-amine Chemical compound CCCCCCCC\C=C/CCCCCCCCN QGLWBTPVKHMVHM-KTKRTIGZSA-N 0.000 claims description 11
- LQJBNNIYVWPHFW-UHFFFAOYSA-N 20:1omega9c fatty acid Natural products CCCCCCCCCCC=CCCCCCCCC(O)=O LQJBNNIYVWPHFW-UHFFFAOYSA-N 0.000 claims description 11
- QSBYPNXLFMSGKH-UHFFFAOYSA-N 9-Heptadecensaeure Natural products CCCCCCCC=CCCCCCCCC(O)=O QSBYPNXLFMSGKH-UHFFFAOYSA-N 0.000 claims description 11
- ZQPPMHVWECSIRJ-UHFFFAOYSA-N Oleic acid Natural products CCCCCCCCC=CCCCCCCCC(O)=O ZQPPMHVWECSIRJ-UHFFFAOYSA-N 0.000 claims description 11
- 239000005642 Oleic acid Substances 0.000 claims description 11
- QXJSBBXBKPUZAA-UHFFFAOYSA-N isooleic acid Natural products CCCCCCCC=CCCCCCCCCC(O)=O QXJSBBXBKPUZAA-UHFFFAOYSA-N 0.000 claims description 11
- ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 claims description 11
- 238000005119 centrifugation Methods 0.000 claims description 10
- 238000010438 heat treatment Methods 0.000 claims description 8
- KLFRPGNCEJNEKU-FDGPNNRMSA-L (z)-4-oxopent-2-en-2-olate;platinum(2+) Chemical compound [Pt+2].C\C([O-])=C\C(C)=O.C\C([O-])=C\C(C)=O KLFRPGNCEJNEKU-FDGPNNRMSA-L 0.000 claims description 7
- SRYDOKOCKWANAE-UHFFFAOYSA-N hexadecane-1,1-diol Chemical compound CCCCCCCCCCCCCCCC(O)O SRYDOKOCKWANAE-UHFFFAOYSA-N 0.000 claims description 7
- XEEYBQQBJWHFJM-UHFFFAOYSA-N iron Substances [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims description 7
- 229910052742 iron Inorganic materials 0.000 claims description 7
- 238000003756 stirring Methods 0.000 claims description 7
- 239000012528 membrane Substances 0.000 claims description 6
- 238000010992 reflux Methods 0.000 claims description 6
- ROFVEXUMMXZLPA-UHFFFAOYSA-N Bipyridyl Chemical compound N1=CC=CC=C1C1=CC=CC=N1 ROFVEXUMMXZLPA-UHFFFAOYSA-N 0.000 claims description 5
- 238000002156 mixing Methods 0.000 claims description 5
- 239000007864 aqueous solution Substances 0.000 claims description 4
- 238000000502 dialysis Methods 0.000 claims description 4
- 238000011534 incubation Methods 0.000 claims description 4
- 239000011261 inert gas Substances 0.000 claims description 4
- 230000001105 regulatory effect Effects 0.000 claims description 4
- 239000003381 stabilizer Substances 0.000 claims description 4
- BTOOAFQCTJZDRC-UHFFFAOYSA-N 1,2-hexadecanediol Chemical compound CCCCCCCCCCCCCCC(O)CO BTOOAFQCTJZDRC-UHFFFAOYSA-N 0.000 claims description 2
- 238000001816 cooling Methods 0.000 claims description 2
- 238000001914 filtration Methods 0.000 claims description 2
- 230000007935 neutral effect Effects 0.000 claims description 2
- 239000000463 material Substances 0.000 abstract description 8
- 230000000259 anti-tumor effect Effects 0.000 abstract description 5
- 230000004044 response Effects 0.000 abstract description 4
- 230000015556 catabolic process Effects 0.000 abstract description 3
- 238000006731 degradation reaction Methods 0.000 abstract description 3
- 230000005934 immune activation Effects 0.000 abstract description 3
- 238000002595 magnetic resonance imaging Methods 0.000 abstract description 3
- 238000004519 manufacturing process Methods 0.000 abstract description 2
- 230000003527 anti-angiogenesis Effects 0.000 abstract 1
- 230000034005 thiol-disulfide exchange Effects 0.000 abstract 1
- RWSXRVCMGQZWBV-WDSKDSINSA-N glutathione Chemical compound OC(=O)[C@@H](N)CCC(=O)N[C@@H](CS)C(=O)NCC(O)=O RWSXRVCMGQZWBV-WDSKDSINSA-N 0.000 description 36
- 239000010949 copper Substances 0.000 description 18
- 229960003180 glutathione Drugs 0.000 description 18
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 15
- 229910052802 copper Inorganic materials 0.000 description 15
- 239000002245 particle Substances 0.000 description 13
- 210000004027 cell Anatomy 0.000 description 12
- 239000000203 mixture Substances 0.000 description 10
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
- 238000012360 testing method Methods 0.000 description 8
- 210000004881 tumor cell Anatomy 0.000 description 8
- 102000008096 B7-H1 Antigen Human genes 0.000 description 6
- 108010074708 B7-H1 Antigen Proteins 0.000 description 6
- 201000011510 cancer Diseases 0.000 description 6
- 229910000365 copper sulfate Inorganic materials 0.000 description 6
- ARUVKPQLZAKDPS-UHFFFAOYSA-L copper(II) sulfate Chemical compound [Cu+2].[O-][S+2]([O-])([O-])[O-] ARUVKPQLZAKDPS-UHFFFAOYSA-L 0.000 description 6
- 239000012299 nitrogen atmosphere Substances 0.000 description 6
- JPVYNHNXODAKFH-UHFFFAOYSA-N Cu2+ Chemical compound [Cu+2] JPVYNHNXODAKFH-UHFFFAOYSA-N 0.000 description 5
- 108010024636 Glutathione Proteins 0.000 description 5
- 229910001431 copper ion Inorganic materials 0.000 description 5
- 238000002474 experimental method Methods 0.000 description 5
- 239000000047 product Substances 0.000 description 5
- 238000011282 treatment Methods 0.000 description 5
- 239000002738 chelating agent Substances 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 239000002105 nanoparticle Substances 0.000 description 4
- 230000017188 evasion or tolerance of host immune response Effects 0.000 description 3
- 230000005764 inhibitory process Effects 0.000 description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- 239000011148 porous material Substances 0.000 description 3
- 239000002244 precipitate Substances 0.000 description 3
- 239000007787 solid Substances 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- 239000000725 suspension Substances 0.000 description 3
- 230000008685 targeting Effects 0.000 description 3
- 238000003260 vortexing Methods 0.000 description 3
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 2
- 108091007744 Programmed cell death receptors Proteins 0.000 description 2
- 238000003917 TEM image Methods 0.000 description 2
- 108090000848 Ubiquitin Proteins 0.000 description 2
- 102000044159 Ubiquitin Human genes 0.000 description 2
- 230000002776 aggregation Effects 0.000 description 2
- 238000004220 aggregation Methods 0.000 description 2
- 230000033115 angiogenesis Effects 0.000 description 2
- 238000011398 antitumor immunotherapy Methods 0.000 description 2
- 230000003833 cell viability Effects 0.000 description 2
- 239000012091 fetal bovine serum Substances 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
- 239000001963 growth medium Substances 0.000 description 2
- 239000003446 ligand Substances 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- 230000001404 mediated effect Effects 0.000 description 2
- 239000002609 medium Substances 0.000 description 2
- 238000012544 monitoring process Methods 0.000 description 2
- 230000035755 proliferation Effects 0.000 description 2
- 238000010186 staining Methods 0.000 description 2
- 238000011269 treatment regimen Methods 0.000 description 2
- 102000020856 Copper Transport Proteins Human genes 0.000 description 1
- 108091004554 Copper Transport Proteins Proteins 0.000 description 1
- 206010010957 Copper deficiency Diseases 0.000 description 1
- 108091006566 Copper transporters Proteins 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 206010015150 Erythema Diseases 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- 229930193140 Neomycin Natural products 0.000 description 1
- 208000003435 Optic Neuritis Diseases 0.000 description 1
- 102000004495 STAT3 Transcription Factor Human genes 0.000 description 1
- 108010017324 STAT3 Transcription Factor Proteins 0.000 description 1
- 210000001744 T-lymphocyte Anatomy 0.000 description 1
- 206010047700 Vomiting Diseases 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 239000002870 angiogenesis inducing agent Substances 0.000 description 1
- 230000001772 anti-angiogenic effect Effects 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 230000005540 biological transmission Effects 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 230000009920 chelation Effects 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 238000002512 chemotherapy Methods 0.000 description 1
- 238000004132 cross linking Methods 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 238000003745 diagnosis Methods 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 210000002889 endothelial cell Anatomy 0.000 description 1
- 102000052116 epidermal growth factor receptor activity proteins Human genes 0.000 description 1
- 108700015053 epidermal growth factor receptor activity proteins Proteins 0.000 description 1
- 231100000321 erythema Toxicity 0.000 description 1
- 230000029142 excretion Effects 0.000 description 1
- 230000009036 growth inhibition Effects 0.000 description 1
- 238000002173 high-resolution transmission electron microscopy Methods 0.000 description 1
- 230000001506 immunosuppresive effect Effects 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 230000010354 integration Effects 0.000 description 1
- 201000002364 leukopenia Diseases 0.000 description 1
- 231100001022 leukopenia Toxicity 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 230000005012 migration Effects 0.000 description 1
- 238000013508 migration Methods 0.000 description 1
- 239000011259 mixed solution Substances 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- YOHYSYJDKVYCJI-UHFFFAOYSA-N n-[3-[[6-[3-(trifluoromethyl)anilino]pyrimidin-4-yl]amino]phenyl]cyclopropanecarboxamide Chemical compound FC(F)(F)C1=CC=CC(NC=2N=CN=C(NC=3C=C(NC(=O)C4CC4)C=CC=3)C=2)=C1 YOHYSYJDKVYCJI-UHFFFAOYSA-N 0.000 description 1
- 229960004927 neomycin Drugs 0.000 description 1
- 238000012758 nuclear staining Methods 0.000 description 1
- 230000026731 phosphorylation Effects 0.000 description 1
- 238000006366 phosphorylation reaction Methods 0.000 description 1
- 230000005180 public health Effects 0.000 description 1
- 238000001959 radiotherapy Methods 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 239000012128 staining reagent Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 230000009897 systematic effect Effects 0.000 description 1
- 231100000057 systemic toxicity Toxicity 0.000 description 1
- 125000003396 thiol group Chemical group [H]S* 0.000 description 1
- 230000005747 tumor angiogenesis Effects 0.000 description 1
- 230000004614 tumor growth Effects 0.000 description 1
- 230000008673 vomiting Effects 0.000 description 1
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
- A61K47/52—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 inorganic compound, e.g. an inorganic ion that is complexed with the active ingredient
-
- 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
- A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
- A61K31/444—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring heteroatom, e.g. amrinone
-
- 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
- A61K47/6921—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 particulate, a powder, an adsorbate, a bead or a sphere
- A61K47/6927—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 particulate, a powder, an adsorbate, a bead or a sphere the form being a solid microparticle having no hollow or gas-filled cores
- A61K47/6929—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 particulate, a powder, an adsorbate, a bead or a sphere the form being a solid microparticle having no hollow or gas-filled cores the form being a nanoparticle, e.g. an immuno-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
- A61K49/06—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
-
- 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
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/04—Immunostimulants
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B82—NANOTECHNOLOGY
- B82Y—SPECIFIC USES OR APPLICATIONS OF NANOSTRUCTURES; MEASUREMENT OR ANALYSIS OF NANOSTRUCTURES; MANUFACTURE OR TREATMENT OF NANOSTRUCTURES
- B82Y25/00—Nanomagnetism, e.g. magnetoimpedance, anisotropic magnetoresistance, giant magnetoresistance or tunneling magnetoresistance
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B82—NANOTECHNOLOGY
- B82Y—SPECIFIC USES OR APPLICATIONS OF NANOSTRUCTURES; MEASUREMENT OR ANALYSIS OF NANOSTRUCTURES; MANUFACTURE OR TREATMENT OF NANOSTRUCTURES
- B82Y40/00—Manufacture or treatment of nanostructures
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B82—NANOTECHNOLOGY
- B82Y—SPECIFIC USES OR APPLICATIONS OF NANOSTRUCTURES; MEASUREMENT OR ANALYSIS OF NANOSTRUCTURES; MANUFACTURE OR TREATMENT OF NANOSTRUCTURES
- B82Y5/00—Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Nanotechnology (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Immunology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Crystallography & Structural Chemistry (AREA)
- Radiology & Medical Imaging (AREA)
- Organic Chemistry (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Condensed Matter Physics & Semiconductors (AREA)
- General Physics & Mathematics (AREA)
- Medical Informatics (AREA)
- Physics & Mathematics (AREA)
- Biotechnology (AREA)
- General Engineering & Computer Science (AREA)
- Biophysics (AREA)
- Manufacturing & Machinery (AREA)
- Molecular Biology (AREA)
- Inorganic Chemistry (AREA)
- Medicinal Preparation (AREA)
Abstract
本发明公开了一种在肿瘤微环境实现原位自组装的多功能纳米材料及其制备方法与应用。其制备方法包括以下步骤:利用高温热降解方法,制备超小FePt纳米合金,并利用DMSA改性成亲水FePt纳米合金FePt@DMSA;随后利用硫醇‑二硫醚交换反应,制得功能化纳米合金FePt@Bpy,并公开了该材料在制备磁共振成像引导的肿瘤抗血管生成和肿瘤免疫激活药物中的应用。本发明制备工艺简单、方便,制备方法适合于量产,制得的功能化纳米合金FePt@Bpy,可以实现肿瘤微环境的响应,具有良好的生物安全性。
Description
技术领域
本发明涉及生物医学材料技术领域,具体涉及一种在肿瘤微环境实现原位自组装的多功能纳米材料及其制备方法与应用。
背景技术
癌症仍然是全球主要的公共卫生问题之一,也是世界上第二大死亡原因。为了解决这一日益增长的负担,并实现更好的癌症治疗方法,除了目前主要的手术、化疗和放疗等治疗方法外,还出现了许多新开发的方法。目前备受瞩目的抗肿瘤免疫疗法,但是由于肿瘤细胞表面高表达程序性死亡受体配体1(PD-L1),与T细胞膜上程序性死亡受体(PD-1)作用后激活免疫抑制信号,导致肿瘤免疫逃逸。因此,PD-L1表达与调控成为了目前抗肿瘤免疫治疗研究热点,以期寻找抑制PD-L1表达的新的肿瘤治疗策略。
大量研究表明,铜离子可以促进肿瘤部位内皮细胞在之间的增殖和迁移,并且促进肿瘤细胞分泌血管生成因子。螯合铜可以通过促进螯合后的排泄,系统地显著降低铜的浓度。螯合肿瘤中的铜离子已被证实是一种有效的、有前途的抗血管生成的癌症治疗策略。另外在许多癌症中,主要的铜转运体CTR-1和PD-L1的表达之间有很强的相关性,但在相应的正常组织中却没有,铜螯合剂可抑制STAT3和EGFR的磷酸化,并促进泛素介导的PD-L1的降解,从而阻断癌症免疫逃逸。然而,由于铜是人体不可缺少的物质,通过注射铜螯合剂系统地去除铜将导致不可避免的严重的副作用,包括红斑病、视神经炎、呕吐和白细胞减少。因此整合一种特定的药物,使铜螯合剂精准在肿瘤内发挥作用,以避免系统性毒性,并能够实时监测对肿瘤产生显著的抑制作用,仍然具有挑战性。
发明内容
为了解决现有技术存在的上述不足,本发明的目的是提供一种在肿瘤微环境实现原位自组装的多功能纳米材料及其制备方法与应用,用于磁共振成像引导的抗肿瘤血管新生和肿瘤免疫激活。
本发明解决上述技术问题的技术方案如下:
一种在肿瘤微环境实现原位自组装的多功能纳米材料的制备方法,包括以下步骤:
(1)FePt纳米合金的合成:将乙酰丙酮铂,1,2-十六烷二醇和二苄醚混合,惰性气体保护下加热反应,然后加入混合稳定剂和二壬羰基铁,加热回流,冷却,洗涤,离心,制得;
(2)FePt@DMSA纳米合金的合成:将步骤(1)制得的FePt纳米合金分散于甲苯中,加入含有DMSA的二甲基亚砜溶液,超声混合,孵育,洗涤,水中分散,透析,离心,调pH至弱碱性,滤膜过滤,调pH至中性,制得;
(3)功能化纳米合金FePt@Bpy的合成:将2,2-联吡啶溶于甲醇,加入步骤(2)制得的FePt@DMSA纳米合金的水溶液,搅拌,离心,洗涤,分散于三蒸水,制得。
进一步地,步骤(1)中十六烷二醇,乙酰丙酮铂和二壬羰基铁的质量比为2:1~3:3~4。
进一步地,步骤(1)中十六烷二醇溶于二苄醚后的浓度为0.01~0.02g/mL。
进一步地,步骤(1)中混合稳定剂由油胺和油酸按体积比1:0.8~1.2混合制得。
进一步地,步骤(1)中惰性气体保护下加热反应的温度为90~120℃,
时间为10~60min。
进一步地,步骤(1)中加热回流的温度为280~300℃,时间为3~4h。
进一步地,步骤(1)中离心的转速为11000~14000rpm,时间为10~15min。
进一步地,步骤(2)中DMSA溶于二甲基亚砜后的浓度为2.5~10mg/mL。
进一步地,步骤(2)中孵育的温度为20~25℃,时间为24~36h。
进一步地,步骤(2)中透析的温度为20~25℃,时间为48~72h。
进一步地,步骤(2)中碱性的pH为8~10。
进一步地,步骤(2)中离心的转速为11000~14000rpm,时间为10~15min。
进一步地,步骤(3)中2,2-联吡啶溶于甲醇后浓度为2.5~5mg/mL。
进一步地,步骤(3)中FePt@DMSA纳米合金的水溶液浓度为1~2mg/mL。
进一步地,步骤(3)中搅拌的时间为20~30h。
进一步地,步骤(3)中离心的转速为11000~14000rpm,时间为10~20min。
进一步地,步骤(1)中洗涤的具体操作为:用乙醇洗涤2~5次。
进一步地,步骤(2)中洗涤的具体操作为:先用乙醇洗涤,再用水洗涤,重复2~5次。
进一步地,步骤(3)中洗涤的具体操作为:用水洗涤2~5次。
采用上述的制备方法制得的多功能纳米材料。
上述多功能纳米材料在制备治疗肿瘤药物中的应用。
本发明具有以下有益效果:
(1)本发明制备的功能化纳米合金FePt@Bpy可以在肿瘤治疗中应用,其主要优势在于可以在肿瘤过表达谷胱甘肽(GSH)的微环境下,材料表面双硫键裂解,暴露出巯基,进一步螯合癌细胞内的铜离子,从而抑制肿瘤血管新生;同时,铜含量减少会促进泛素介导的PD-L1的降解,阻断癌症免疫逃逸,从而抑制肿瘤生长,提高小鼠生存率。此外,超小FePt纳米材料在铜离子的交联下,组装成纳米簇,增强T2加权磁共振成像,最终实现通过铜缺乏引发抗肿瘤血管新生和肿瘤免疫激活的磁共振诊疗一体化,该项目的实施将有助于为肿瘤治疗开辟新方法提供借鉴。
(2)本发明制备工艺简单、方便,制备方法适合于量产,制得的功能化纳米合金FePt@Bpy,可以实现肿瘤微环境的响应,具有良好的生物安全性。
附图说明
图1为试验例1FePt@Bpy纳米合金的TEM实验结果,其中,(a)为FePt@Bpy低倍率TEM图像,(b)为FePt@Bpy高倍率TEM图像,(c)为FePt@Bpy高分辨率TEM图像,(d)为FePt@Bpy的水合粒径图;
图2为试验例1FePt@Bpy纳米合金的螯合铜能力测试实验结果,其中,(a)为FePt@Bpy加谷胱甘肽、硫酸铜溶液、谷胱甘肽和硫酸铜溶液变化,(b)为不同浓度GSH处理FePt@Bpy螯合铜后的水合粒径图,(c)为FePt@Bpy+Cu2++1mmol/L GSH TEM图,(d)为FePt@Bpy+Cu2 ++2mmol/LGSH TEM图,(e)为FePt@Bpy+Cu2++5mmol/L GSH TEM图;
图3为试验例2FePt@Bpy纳米合金抗肿瘤效应测定实验结果,其中,(a)为用不同浓度的FePt@Bpy处理4T1和PC3细胞24h的细胞相对存活率,(b)为用不同浓度的FePt@Bpy处理C166和L292细胞24h的细胞相对存活率;
图4为试验例3FePt@Bpy纳米合金肿瘤靶向能力测定实验结果的激光共聚焦图像。
具体实施方式
以下所举实例只用于解释本发明,并非用于限定本发明的范围。实施例中未注明具体条件者,按照常规条件或制造商建议的条件进行。所用试剂或仪器未注明生产厂商者,均为可以通过市售购买获得的常规产品。
实施例1:
一种可在肿瘤微环境实现原位自组装的功能化纳米合金FePt@Bpy的制备方法,包括以下步骤:
(1)FePt纳米合金的合成:将0.2001g十六烷二醇,0.1001g乙酰丙酮铂和20mL二苄醚,均匀混合于三颈瓶中,在氮气氛围下加热至100℃,加入油酸170μL与油胺170μL。30min后,加入500μL油酸与500μL油胺,随后加入0.3653g二壬羰基铁,设置温度291.2℃,加热回流3h。待反应结束后,该反应体系在氮气氛围下冷却至室温,通过加入乙醇从正己烷悬液中沉淀,离心3次,每次离心转速14000rpm,时间10min,收集沉淀得到超小FePt纳米合金。
(2)FePt@DMSA纳米合金的合成:将步骤(1)制得的FePt纳米合金重新分散在20mL甲苯中,加入5mL含有50mg DMSA的DMSO溶液中,超声混合,将混合物在室温下在旋转搅拌器中孵育48h。反应结束后,丢弃含有油酸和油胺的半透明溶剂,将附着在烧瓶壁上的黑色颗粒通过超声波和涡旋重新分散在乙醇中。将该混合物离心,并在乙醇中重新分散3次,以清洗颗粒。最后,将黑色颗粒重新分散在三蒸水中,用pH为10的氢氧化钠碱,在三蒸水中透析约48小时,通过0.1μm孔膜过滤,将pH调整为7,制得FePt@DMSA纳米合金。
(3)功能化纳米合金FePt@Bpy:将100mg Py-SS-Py分散于20mL甲醇中,再加入1mL1mg/mL的FePt@DMSA纳米合金溶液,在室温黑暗条件下搅拌24h。反应结束后,通过离心分离所得固体,用三蒸水和乙醇洗涤3次。然后通过离心收集所得产物,将产物分散到三蒸水中,制得。
实施例2:
一种可在肿瘤微环境实现原位自组装的功能化纳米合金FePt@Bpy的制备方法,包括以下步骤:
(1)FePt纳米合金的合成:将0.2001g十六烷二醇,0.2001g乙酰丙酮铂和20mL二苄醚,均匀混合于三颈瓶中,在氮气氛围下加热至100℃,加入油酸170μL与油胺170μL。30min后,加入500μL油酸与500μL油胺,随后加入0.3153g二壬羰基铁,设置温度280℃,加热回流4h。待反应结束后,该反应体系在氮气氛围下冷却至室温,通过加入乙醇从正己烷悬液中沉淀,离心3次,每次离心转速12000rpm,时间15min,收集沉淀得到超小FePt纳米合金。
(2)FePt@DMSA纳米合金的合成:将步骤(1)制得的FePt纳米合金重新分散在20mL甲苯中,加入5mL含有40mg DMSA的DMSO溶液中,超声混合,将混合物在室温下在旋转搅拌器中孵育48h。反应结束后,丢弃含有油酸和油胺的半透明溶剂,将附着在烧瓶壁上的黑色颗粒通过超声波和涡旋重新分散在乙醇中。将该混合物离心,并在乙醇中重新分散3次,以清洗颗粒。最后,将黑色颗粒重新分散在三蒸水中,用pH为10的氢氧化钠碱,在三蒸水中透析约48小时,通过0.1μm孔膜过滤,将pH调整为7,制得FePt@DMSA纳米合金。
(3)功能化纳米合金FePt@Bpy:将80mg Py-SS-Py分散于20mL甲醇中,再加入1mL1mg/mL的FePt@DMSA纳米合金溶液,在室温黑暗条件下搅拌24h。反应结束后,通过离心分离所得固体,用三蒸水和乙醇洗涤3次。然后通过离心收集所得产物,将产物分散到三蒸水中,制得。
实施例3:
一种可在肿瘤微环境实现原位自组装的功能化纳米合金FePt@Bpy的制备方法,包括以下步骤:
(1)FePt纳米合金的合成:将0.2001g十六烷二醇,0.1501g乙酰丙酮铂和20mL二苄醚,均匀混合于三颈瓶中,在氮气氛围下加热至100℃,加入油酸170μL与油胺170μL。30min后,加入500μL油酸与500μL油胺,随后加入0.3842g二壬羰基铁,设置温度291.2℃,加热回流3h。待反应结束后,该反应体系在氮气氛围下冷却至室温,通过加入乙醇从正己烷悬液中沉淀,离心3次,每次离心转速14000rpm,时间10min,收集沉淀得到超小FePt纳米合金。
(2)FePt@DMSA纳米合金的合成:将步骤(1)制得的FePt纳米合金重新分散在20mL甲苯中,加入5mL含有30mg DMSA的DMSO溶液中,超声混合,将混合物在室温下在旋转搅拌器中孵育48h。反应结束后,丢弃含有油酸和油胺的半透明溶剂,将附着在烧瓶壁上的黑色颗粒通过超声波和涡旋重新分散在乙醇中。将该混合物离心,并在乙醇中重新分散3次,以清洗颗粒。最后,将黑色颗粒重新分散在三蒸水中,用氢氧化钠将溶液pH调整为10,在三蒸水中透析约48小时,通过0.1μm孔膜过滤,将pH调整为7,制得FePt@DMSA纳米合金。
(3)功能化纳米合金FePt@Bpy:将50mg Py-SS-Py分散于20mL甲醇中,再加入1mL1mg/mL的FePt@DMSA纳米合金溶液,在室温黑暗条件下搅拌24h。反应结束后,通过离心分离所得固体,用三蒸水和乙醇洗涤3次。然后通过离心收集所得产物,将产物分散到三蒸水中,制得。
试验例1:FePt@Bpy纳米合金性能测定
取实施例1制得的FePt@Bpy纳米合金进行实验。
(1)通过透射电子显微镜(TEM)对实施例1制得的FePt@Bpy纳米合金进行形貌表征,实验结果如图1所示,TEM结果表明该条件下合成的FePt@Bpy纳米合金,形态均一,尺寸约为4nm,为分散性良好的超小合金纳米颗粒。
(2)将FePt@Bpy纳米合金分别与硫酸铜溶液,GSH溶液以及硫酸铜和GSH混合溶液混匀,探究其是否具备谷胱甘肽响应螯合铜功能;将FePt@Bpy纳米合金与硫酸铜、不同浓度的GSH溶液(0.5~5mmol/L)混匀,探讨GSH浓度对FePt@Bpy纳米合金螯合铜能力的影响。
实验结果如图2所示,图2(a)为FePt@Bpy纳米合金加谷胱甘肽、硫酸铜溶液、谷胱甘肽和硫酸铜溶液变化,结果表明FePt@Bpy纳米合金与单纯的硫酸铜溶液、GSH不发生螯合。但是,一旦同时加入GSH与硫酸铜溶液之后材料发生聚集,证明该材料具有谷胱甘肽响应螯合铜功能。图2(b)为不同浓度GSH溶液处理FePt@Bpy纳米合金螯合铜后的水和粒径图,结果表明,随着GSH溶液浓度增大,材料团聚更明显,粒径更大,证明该材料随着GSH浓度增大可以增强螯合铜能力。因此,本发明制得的FePt@Bpy纳米合金是一种肿瘤微环境高谷胱甘肽响应的铜螯合剂,可特异性降低肿瘤部位的铜离子浓度。
试验例2:FePt@Bpy纳米合金抗肿瘤效应测定
取实施例1制得的FePt@Bpy纳米合金进行实验。
(1)肿瘤细胞的培养
分别以104个/孔的密度将4T1、PC3、C166、L929细胞接种在96孔板中,用1640培养基培养12h。12h后用不同浓度的材料孵育细胞24h。
(2)MTT检测FePt@Bpy纳米合金对肿瘤细胞的增殖抑制效果将96孔板的培养基移除,每孔加入培养基与MTT按体积比9:1的比例混合的溶液,继续在培养箱孵育4h后,移除液体,每孔加入250μL二甲基亚砜溶液,轻轻摇匀后在490nm处,用酶标仪检测。
实验结果如图3所示,MTT结果表明FePt@Bpy纳米合金对4T1、PC3肿瘤细胞具有浓度依赖性的生长抑制效果,对正常细胞无抑制效果。
试验例3:FePt@Bpy纳米合金肿瘤靶向能力测定
取实施例1制得的FePt@Bpy纳米合金进行实验。
(1)肿瘤细胞的培养
将PC3细胞,以1×105个/盘的密度接种于共聚焦皿中,用含10%胎牛血清(FBS)和1%青链霉素双抗的1640培养基,培养12h。
(2)肿瘤细胞对纳米颗粒的摄取情况的监测将制备的装载异硫氰酸荧光素的FePt@Bpy纳米合金以40μg/mL的浓度对细胞进行孵育,在6h后用Hochest 33342活细胞核染色试剂对细胞进行染色,染色后进行激光共聚焦的拍摄,监测细胞纳米颗粒的摄取情况。
实验结果如图4所示,随着纳米材料孵育的肿瘤细胞随浓度增加,FITC荧光信号增多,即细胞摄取纳米颗粒数量增多,表明本发明制得的FePt@Bpy纳米合金具备优异的肿瘤靶向能力。
以上所述仅为本发明的较佳实施例,并不用以限制本发明,凡在本发明的精神和原则之内,所作的任何修改、等同替换、改进等,均应包含在本发明的保护范围之内。
Claims (10)
1.一种在肿瘤微环境实现原位自组装的多功能纳米材料的制备方法,其特征在于,包括以下步骤:
(1)FePt纳米合金的合成:将乙酰丙酮铂,1,2-十六烷二醇和二苄醚混合,惰性气体保护下加热反应,然后加入混合稳定剂和二壬羰基铁,加热回流,冷却,洗涤,离心,制得;
(2)FePt@DMSA纳米合金的合成:将步骤(1)制得的FePt纳米合金分散于甲苯中,加入含有DMSA的二甲基亚砜溶液,超声混合,孵育,洗涤,水中分散,透析,离心,调pH至弱碱性,滤膜过滤,调pH至中性,制得;
(3)功能化纳米合金FePt@Bpy的合成:将2,2-联吡啶溶于甲醇,加入步骤(2)制得的FePt@DMSA纳米合金的水溶液,搅拌,离心,洗涤,分散于三蒸水,制得。
2.根据权利要求1所述的在肿瘤微环境实现原位自组装的多功能纳米材料的制备方法,其特征在于,步骤(1)所述十六烷二醇,所述乙酰丙酮铂和所述二壬羰基铁的质量比为2:1~3:3~4;所述十六烷二醇溶于所述二苄醚后的浓度为0.01~0.02g/mL;所述混合稳定剂由油胺和油酸按体积比1:0.8~1.2混合制得。
3.根据权利要求1所述的在肿瘤微环境实现原位自组装的多功能纳米材料的制备方法,其特征在于,步骤(1)所述惰性气体保护下加热反应的温度为90~120℃,时间为10~60min;所述加热回流的温度为280~300℃,时间为3~4h;所述离心的转速为11000~14000rpm,时间为10~15min。
4.根据权利要求1所述的在肿瘤微环境实现原位自组装的多功能纳米材料的制备方法,其特征在于,步骤(2)所述DMSA溶于所述二甲基亚砜后的浓度为2.5~10mg/mL。
5.根据权利要求1所述的在肿瘤微环境实现原位自组装的多功能纳米材料的制备方法,其特征在于,步骤(2)所述孵育的温度为20~25℃,时间为24~36h;所述透析的温度为20~25℃,时间为48~72h;所述碱性的pH值为8~10;所述离心转速为11000~14000rpm,时间为10~15min。
6.根据权利要求1所述的在肿瘤微环境实现原位自组装的多功能纳米材料的制备方法,其特征在于,步骤(3)所述2,2-联吡啶溶于甲醇后浓度为2.5~5mg/mL;所述FePt@DMSA纳米合金的水溶液浓度为1~2mg/mL。
7.根据权利要求1所述的在肿瘤微环境实现原位自组装的多功能纳米材料的制备方法,其特征在于,步骤(3)所述搅拌时间为20~30h;所述离心转速为11000~14000rpm,时间为10~20min。
8.根据权利要求1所述的在肿瘤微环境实现原位自组装的多功能纳米材料的制备方法,其特征在于,步骤(1)所述洗涤的具体操作为:用乙醇洗涤2~5次;步骤(2)所述洗涤的具体操作为:先用乙醇洗涤,再用水洗涤,重复2~5次;步骤(3)所述洗涤的具体操作为:用水洗涤2~5次。
9.采用权利要求1~8任一项所述的制备方法制得的多功能纳米材料。
10.权利要求9所述多功能纳米材料在制备治疗肿瘤药物中的应用。
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202310983615.XA CN118079023A (zh) | 2023-08-04 | 2023-08-04 | 一种在肿瘤微环境实现原位自组装的多功能纳米材料及其制备方法与应用 |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202310983615.XA CN118079023A (zh) | 2023-08-04 | 2023-08-04 | 一种在肿瘤微环境实现原位自组装的多功能纳米材料及其制备方法与应用 |
Publications (1)
Publication Number | Publication Date |
---|---|
CN118079023A true CN118079023A (zh) | 2024-05-28 |
Family
ID=91153801
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN202310983615.XA Pending CN118079023A (zh) | 2023-08-04 | 2023-08-04 | 一种在肿瘤微环境实现原位自组装的多功能纳米材料及其制备方法与应用 |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN118079023A (zh) |
-
2023
- 2023-08-04 CN CN202310983615.XA patent/CN118079023A/zh active Pending
Similar Documents
Publication | Publication Date | Title |
---|---|---|
Ling et al. | Synthesis, surface modification, and applications of magnetic iron oxide nanoparticles | |
Wu et al. | Gadolinium-chelate functionalized bismuth nanotheranostic agent for in vivo MRI/CT/PAI imaging-guided photothermal cancer therapy | |
Na et al. | Versatile PEG-derivatized phosphine oxide ligands for water-dispersible metal oxide nanocrystals | |
Zhang et al. | Intracellular pH-sensitive supramolecular amphiphiles based on host–guest recognition between benzimidazole and β-cyclodextrin as potential drug delivery vehicles | |
US20100119458A1 (en) | Compositions Containing Metal Oxide Particles and Their Use | |
Chan et al. | Integrated therapy platform of exosomal system: hybrid inorganic/organic nanoparticles with exosomes for cancer treatment | |
CN109364899B (zh) | 磁性zif-8纳米复合颗粒的制备方法及其产品 | |
Deol et al. | Stability, cytotoxicity and cell uptake of water-soluble dendron–conjugated gold nanoparticles with 3, 12 and 17 nm cores | |
Fahmi et al. | Development of bovine serum albumin-modified hybrid nanoclusters for magnetofluorescence imaging and drug delivery | |
SG192062A1 (en) | Metal-salen complex compound and production method for same | |
WO2013134089A1 (en) | Nanoparticles coated with amphiphilic block copolymers | |
CN107224589B (zh) | 一种输送抗体用于肿瘤免疫治疗的mr成像聚合物胶束及其制备方法 | |
CN114177291B (zh) | 一种二硫化钼药物传递系统及其制备方法和应用 | |
EP3904294A1 (en) | Method for producing nanoparticles including metal particles containing iron oxide having at least one hydrophilic ligand coordinated thereto | |
KR20090033155A (ko) | 자성 나노복합체, 상기를 포함하는 조영제 조성물 및 약제학적 조성물 | |
CN113230418A (zh) | 一种超小核壳结构铁纳米颗粒的制备方法及应用 | |
CN118079023A (zh) | 一种在肿瘤微环境实现原位自组装的多功能纳米材料及其制备方法与应用 | |
CN109939081B (zh) | F3多肽靶向的纳米有机金属框架材料(nMOFs)及其制备方法 | |
EP3922271A1 (en) | Ultrafine iron oxide nanoparticle-based magnetic resonance imaging t1 contrast agent | |
WO2020057086A1 (zh) | 一种Fe 3+/2+-NO供体混价配位聚合物及其应用 | |
CN110623938B (zh) | 一种mpc修饰的树状大分子包裹纳米金颗粒及其制备和应用 | |
JPWO2019004297A1 (ja) | ナノ粒子、これを含む磁気共鳴イメージング用造影剤及びリガンド化合物 | |
CN109276720B (zh) | 一种金属-有机物配合物纳米材料及其制备方法和应用 | |
Wang et al. | One-pot reaction for the large-scale synthesis of hyperbranched polyglycerol-grafted Fe 3 O 4 nanoparticles | |
CN108314786B (zh) | 一种齿状聚合物、利用其修饰氧化铁纳米颗粒的方法及由该方法得到的产品 |
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 |