CN112516336B - 一种用于急性肾损伤的纳米酶诊疗剂及其制备方法与应用 - Google Patents
一种用于急性肾损伤的纳米酶诊疗剂及其制备方法与应用 Download PDFInfo
- Publication number
- CN112516336B CN112516336B CN202011328063.1A CN202011328063A CN112516336B CN 112516336 B CN112516336 B CN 112516336B CN 202011328063 A CN202011328063 A CN 202011328063A CN 112516336 B CN112516336 B CN 112516336B
- Authority
- CN
- China
- Prior art keywords
- nano
- treatment agent
- diagnosis
- enzyme
- enzyme diagnosis
- 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
- 238000011282 treatment Methods 0.000 title claims abstract description 71
- 238000003745 diagnosis Methods 0.000 title claims abstract description 58
- 102000004190 Enzymes Human genes 0.000 title claims abstract description 57
- 108090000790 Enzymes Proteins 0.000 title claims abstract description 57
- 201000011040 acute kidney failure Diseases 0.000 title claims abstract description 38
- 208000009304 Acute Kidney Injury Diseases 0.000 title claims abstract description 36
- 208000033626 Renal failure acute Diseases 0.000 title claims abstract description 36
- 238000002360 preparation method Methods 0.000 title claims abstract description 14
- 239000003795 chemical substances by application Substances 0.000 claims abstract description 60
- 239000002105 nanoparticle Substances 0.000 claims abstract description 30
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims abstract description 28
- 239000003446 ligand Substances 0.000 claims abstract description 28
- DCYOBGZUOMKFPA-UHFFFAOYSA-N iron(2+);iron(3+);octadecacyanide Chemical compound [Fe+2].[Fe+2].[Fe+2].[Fe+3].[Fe+3].[Fe+3].[Fe+3].N#[C-].N#[C-].N#[C-].N#[C-].N#[C-].N#[C-].N#[C-].N#[C-].N#[C-].N#[C-].N#[C-].N#[C-].N#[C-].N#[C-].N#[C-].N#[C-].N#[C-].N#[C-] DCYOBGZUOMKFPA-UHFFFAOYSA-N 0.000 claims abstract description 25
- 229960003351 prussian blue Drugs 0.000 claims abstract description 25
- 239000013225 prussian blue Substances 0.000 claims abstract description 25
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 14
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims abstract description 13
- 239000001301 oxygen Substances 0.000 claims abstract description 13
- 229910052760 oxygen Inorganic materials 0.000 claims abstract description 13
- 229920001661 Chitosan Polymers 0.000 claims description 10
- 238000003756 stirring Methods 0.000 claims description 10
- 238000010438 heat treatment Methods 0.000 claims description 9
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 9
- 239000011259 mixed solution Substances 0.000 claims description 8
- 238000005406 washing Methods 0.000 claims description 6
- YAGKRVSRTSUGEY-UHFFFAOYSA-N ferricyanide Chemical class [Fe+3].N#[C-].N#[C-].N#[C-].N#[C-].N#[C-].N#[C-] YAGKRVSRTSUGEY-UHFFFAOYSA-N 0.000 claims description 5
- 150000002505 iron Chemical class 0.000 claims description 5
- NAVJNPDLSKEXSP-UHFFFAOYSA-N Fe(CN)2 Chemical class N#C[Fe]C#N NAVJNPDLSKEXSP-UHFFFAOYSA-N 0.000 claims description 4
- 238000002156 mixing Methods 0.000 claims description 4
- 150000003839 salts Chemical class 0.000 claims description 4
- 239000012798 spherical particle Substances 0.000 claims description 3
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 2
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 abstract description 25
- 239000000032 diagnostic agent Substances 0.000 abstract description 19
- 229940039227 diagnostic agent Drugs 0.000 abstract description 19
- 210000003734 kidney Anatomy 0.000 abstract description 16
- 230000000694 effects Effects 0.000 abstract description 11
- 239000003814 drug Substances 0.000 abstract description 10
- DQLATGHUWYMOKM-UHFFFAOYSA-L cisplatin Chemical compound N[Pt](N)(Cl)Cl DQLATGHUWYMOKM-UHFFFAOYSA-L 0.000 abstract description 9
- 229960004316 cisplatin Drugs 0.000 abstract description 9
- 238000003384 imaging method Methods 0.000 abstract description 9
- 238000013421 nuclear magnetic resonance imaging Methods 0.000 abstract description 7
- 229940124597 therapeutic agent Drugs 0.000 abstract description 7
- 239000002872 contrast media Substances 0.000 abstract description 5
- 238000005516 engineering process Methods 0.000 abstract description 4
- 241000699670 Mus sp. Species 0.000 description 29
- 210000004027 cell Anatomy 0.000 description 17
- 239000003153 chemical reaction reagent Substances 0.000 description 17
- 208000012998 acute renal failure Diseases 0.000 description 14
- JKOQGQFVAUAYPM-UHFFFAOYSA-N amifostine Chemical compound NCCCNCCSP(O)(O)=O JKOQGQFVAUAYPM-UHFFFAOYSA-N 0.000 description 9
- 229960001097 amifostine Drugs 0.000 description 9
- -1 potassium ferricyanide Chemical compound 0.000 description 9
- 239000000243 solution Substances 0.000 description 9
- 241000699666 Mus <mouse, genus> Species 0.000 description 8
- DDRJAANPRJIHGJ-UHFFFAOYSA-N creatinine Chemical compound CN1CC(=O)NC1=N DDRJAANPRJIHGJ-UHFFFAOYSA-N 0.000 description 8
- 235000011187 glycerol Nutrition 0.000 description 8
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 6
- OHDRQQURAXLVGJ-HLVWOLMTSA-N azane;(2e)-3-ethyl-2-[(e)-(3-ethyl-6-sulfo-1,3-benzothiazol-2-ylidene)hydrazinylidene]-1,3-benzothiazole-6-sulfonic acid Chemical compound [NH4+].[NH4+].S/1C2=CC(S([O-])(=O)=O)=CC=C2N(CC)C\1=N/N=C1/SC2=CC(S([O-])(=O)=O)=CC=C2N1CC OHDRQQURAXLVGJ-HLVWOLMTSA-N 0.000 description 6
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 6
- 239000008363 phosphate buffer Substances 0.000 description 6
- 210000004369 blood Anatomy 0.000 description 5
- 239000008280 blood Substances 0.000 description 5
- HHEAADYXPMHMCT-UHFFFAOYSA-N dpph Chemical compound [O-][N+](=O)C1=CC([N+](=O)[O-])=CC([N+]([O-])=O)=C1[N]N(C=1C=CC=CC=1)C1=CC=CC=C1 HHEAADYXPMHMCT-UHFFFAOYSA-N 0.000 description 5
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 4
- 241001465754 Metazoa Species 0.000 description 4
- MWUXSHHQAYIFBG-UHFFFAOYSA-N Nitric oxide Chemical compound O=[N] MWUXSHHQAYIFBG-UHFFFAOYSA-N 0.000 description 4
- 230000009286 beneficial effect Effects 0.000 description 4
- 230000003833 cell viability Effects 0.000 description 4
- 229940109239 creatinine Drugs 0.000 description 4
- 239000000523 sample Substances 0.000 description 4
- 210000002966 serum Anatomy 0.000 description 4
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
- PNNCWTXUWKENPE-UHFFFAOYSA-N [N].NC(N)=O Chemical compound [N].NC(N)=O PNNCWTXUWKENPE-UHFFFAOYSA-N 0.000 description 3
- 239000003963 antioxidant agent Substances 0.000 description 3
- 238000010586 diagram Methods 0.000 description 3
- 229960002089 ferrous chloride Drugs 0.000 description 3
- NMCUIPGRVMDVDB-UHFFFAOYSA-L iron dichloride Chemical compound Cl[Fe]Cl NMCUIPGRVMDVDB-UHFFFAOYSA-L 0.000 description 3
- 210000003292 kidney cell Anatomy 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 239000002609 medium Substances 0.000 description 3
- 238000000034 method Methods 0.000 description 3
- 150000003254 radicals Chemical class 0.000 description 3
- 229940126586 small molecule drug Drugs 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- 239000002202 Polyethylene glycol Substances 0.000 description 2
- 230000002292 Radical scavenging effect Effects 0.000 description 2
- 238000002441 X-ray diffraction Methods 0.000 description 2
- 238000009825 accumulation Methods 0.000 description 2
- 238000000089 atomic force micrograph Methods 0.000 description 2
- 229920001400 block copolymer Polymers 0.000 description 2
- 230000037396 body weight Effects 0.000 description 2
- 238000012258 culturing Methods 0.000 description 2
- 230000001419 dependent effect Effects 0.000 description 2
- 230000007760 free radical scavenging Effects 0.000 description 2
- 239000001963 growth medium Substances 0.000 description 2
- 230000036541 health Effects 0.000 description 2
- TUJKJAMUKRIRHC-UHFFFAOYSA-N hydroxyl Chemical compound [OH] TUJKJAMUKRIRHC-UHFFFAOYSA-N 0.000 description 2
- 238000010255 intramuscular injection Methods 0.000 description 2
- 239000007927 intramuscular injection Substances 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- CMFNMSMUKZHDEY-UHFFFAOYSA-M peroxynitrite Chemical compound [O-]ON=O CMFNMSMUKZHDEY-UHFFFAOYSA-M 0.000 description 2
- 229920001223 polyethylene glycol Polymers 0.000 description 2
- 229920002503 polyoxyethylene-polyoxypropylene Polymers 0.000 description 2
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 2
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 2
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 2
- 239000003642 reactive oxygen metabolite Substances 0.000 description 2
- 230000002000 scavenging effect Effects 0.000 description 2
- 230000004083 survival effect Effects 0.000 description 2
- 230000002194 synthesizing effect Effects 0.000 description 2
- 102000004506 Blood Proteins Human genes 0.000 description 1
- 108010017384 Blood Proteins Proteins 0.000 description 1
- 229910021578 Iron(III) chloride Inorganic materials 0.000 description 1
- PWKSKIMOESPYIA-BYPYZUCNSA-N L-N-acetyl-Cysteine Chemical compound CC(=O)N[C@@H](CS)C(O)=O PWKSKIMOESPYIA-BYPYZUCNSA-N 0.000 description 1
- 108091005804 Peptidases Proteins 0.000 description 1
- 239000004365 Protease Substances 0.000 description 1
- 102100037486 Reverse transcriptase/ribonuclease H Human genes 0.000 description 1
- OUUQCZGPVNCOIJ-UHFFFAOYSA-M Superoxide Chemical compound [O-][O] OUUQCZGPVNCOIJ-UHFFFAOYSA-M 0.000 description 1
- 238000002835 absorbance Methods 0.000 description 1
- 238000000862 absorption spectrum Methods 0.000 description 1
- 229960004308 acetylcysteine Drugs 0.000 description 1
- 238000009098 adjuvant therapy Methods 0.000 description 1
- 230000003078 antioxidant effect Effects 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 238000004140 cleaning Methods 0.000 description 1
- 231100000135 cytotoxicity Toxicity 0.000 description 1
- 230000003013 cytotoxicity Effects 0.000 description 1
- 238000004042 decolorization Methods 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- QKUSRAKPUWQSJS-UHFFFAOYSA-N diazanium 3-ethyl-2H-1,3-benzothiazole-6-sulfonate Chemical compound [NH4+].[NH4+].[O-]S(=O)(=O)C1=CC=C2N(CC)CSC2=C1.[O-]S(=O)(=O)C1=CC=C2N(CC)CSC2=C1 QKUSRAKPUWQSJS-UHFFFAOYSA-N 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 210000002308 embryonic cell Anatomy 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 230000005802 health problem Effects 0.000 description 1
- 208000006750 hematuria Diseases 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000011081 inoculation Methods 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 239000007928 intraperitoneal injection Substances 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- XEEYBQQBJWHFJM-UHFFFAOYSA-N iron Substances [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 1
- RBTARNINKXHZNM-UHFFFAOYSA-K iron trichloride Chemical compound Cl[Fe](Cl)Cl RBTARNINKXHZNM-UHFFFAOYSA-K 0.000 description 1
- 238000002595 magnetic resonance imaging Methods 0.000 description 1
- 210000001161 mammalian embryo Anatomy 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 238000010172 mouse model Methods 0.000 description 1
- 239000002086 nanomaterial Substances 0.000 description 1
- 150000002831 nitrogen free-radicals Chemical class 0.000 description 1
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen(.) Chemical compound [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
- 238000000643 oven drying Methods 0.000 description 1
- 230000008506 pathogenesis Effects 0.000 description 1
- 239000008055 phosphate buffer solution Substances 0.000 description 1
- 239000000276 potassium ferrocyanide Substances 0.000 description 1
- USHAGKDGDHPEEY-UHFFFAOYSA-L potassium persulfate Chemical compound [K+].[K+].[O-]S(=O)(=O)OOS([O-])(=O)=O USHAGKDGDHPEEY-UHFFFAOYSA-L 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 239000007845 reactive nitrogen species Substances 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 230000000087 stabilizing effect Effects 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 238000001308 synthesis method Methods 0.000 description 1
- XOGGUFAVLNCTRS-UHFFFAOYSA-N tetrapotassium;iron(2+);hexacyanide Chemical compound [K+].[K+].[K+].[K+].[Fe+2].N#[C-].N#[C-].N#[C-].N#[C-].N#[C-].N#[C-] XOGGUFAVLNCTRS-UHFFFAOYSA-N 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 238000002054 transplantation Methods 0.000 description 1
- 230000035899 viability Effects 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K49/00—Preparations for testing in vivo
- A61K49/22—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
- A61K33/00—Medicinal preparations containing inorganic active ingredients
- A61K33/24—Heavy metals; Compounds thereof
- A61K33/26—Iron; Compounds thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K49/00—Preparations for testing in vivo
- A61K49/0002—General or multifunctional contrast agents, e.g. chelated agents
-
- 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
- A61K49/12—Macromolecular 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
- A61K49/1821—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations characterised by a special physical form, e.g. emulsions, microcapsules, liposomes particles, e.g. uncoated or non-functionalised microparticles or nanoparticles coated or functionalised microparticles or nanoparticles
- A61K49/1824—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations characterised by a special physical form, e.g. emulsions, microcapsules, liposomes particles, e.g. uncoated or non-functionalised microparticles or nanoparticles coated or functionalised microparticles or nanoparticles coated or functionalised nanoparticles
- A61K49/1827—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations characterised by a special physical form, e.g. emulsions, microcapsules, liposomes particles, e.g. uncoated or non-functionalised microparticles or nanoparticles coated or functionalised microparticles or nanoparticles coated or functionalised nanoparticles having a (super)(para)magnetic core, being a solid MRI-active material, e.g. magnetite, or composed of a plurality of MRI-active, organic agents, e.g. Gd-chelates, or nuclei, e.g. Eu3+, encapsulated or entrapped in the core of the coated or functionalised nanoparticle
- A61K49/1851—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations characterised by a special physical form, e.g. emulsions, microcapsules, liposomes particles, e.g. uncoated or non-functionalised microparticles or nanoparticles coated or functionalised microparticles or nanoparticles coated or functionalised nanoparticles having a (super)(para)magnetic core, being a solid MRI-active material, e.g. magnetite, or composed of a plurality of MRI-active, organic agents, e.g. Gd-chelates, or nuclei, e.g. Eu3+, encapsulated or entrapped in the core of the coated or functionalised nanoparticle having a (super)(para)magnetic core coated or functionalised with an organic macromolecular compound, i.e. oligomeric, polymeric, dendrimeric organic molecule
- A61K49/1863—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations characterised by a special physical form, e.g. emulsions, microcapsules, liposomes particles, e.g. uncoated or non-functionalised microparticles or nanoparticles coated or functionalised microparticles or nanoparticles coated or functionalised nanoparticles having a (super)(para)magnetic core, being a solid MRI-active material, e.g. magnetite, or composed of a plurality of MRI-active, organic agents, e.g. Gd-chelates, or nuclei, e.g. Eu3+, encapsulated or entrapped in the core of the coated or functionalised nanoparticle having a (super)(para)magnetic core coated or functionalised with an organic macromolecular compound, i.e. oligomeric, polymeric, dendrimeric organic molecule the organic macromolecular compound being a polysaccharide or derivative thereof, e.g. chitosan, chitin, cellulose, pectin, starch
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
- A61K9/51—Nanocapsules; Nanoparticles
- A61K9/5107—Excipients; Inactive ingredients
- A61K9/513—Organic macromolecular compounds; Dendrimers
- A61K9/5161—Polysaccharides, e.g. alginate, chitosan, cellulose derivatives; Cyclodextrin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/12—Drugs for disorders of the urinary system of the kidneys
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Engineering & Computer Science (AREA)
- Epidemiology (AREA)
- Nanotechnology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Radiology & Medical Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Physics & Mathematics (AREA)
- Organic Chemistry (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Acoustics & Sound (AREA)
- Inorganic Chemistry (AREA)
- Immunology (AREA)
- Molecular Biology (AREA)
- Urology & Nephrology (AREA)
- Biomedical Technology (AREA)
- Optics & Photonics (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
Abstract
本发明公开了一种用于急性肾损伤的纳米酶诊疗剂及其制备方法与应用,所述纳米酶诊疗剂包括:普鲁士蓝纳米颗粒,结合在所述普鲁士蓝纳米颗粒表面的表面配体。本发明纳米酶诊疗剂包括表面配体(CS)以及由所述表面配体保护的普鲁士蓝纳米颗粒(PB NZs)。本发明的纳米酶诊疗剂具有超小的尺寸,能够有效的富集于小鼠肾脏,能够清除肾小管内大量的活性氧或活性氮以缓解和治疗甘油或顺铂诱导的急性肾损伤,并且可作为核磁共振成像、光声成像技术的造影剂。另外,这些纳米酶诊疗剂具有良好的治疗效果,同时具有优异的生物相容性和生物安全性。
Description
技术领域
本发明涉及生物医学材料技术领域,尤其涉及一种用于急性肾损伤的纳米酶诊疗剂及其制备方法与应用。
背景技术
急性肾损伤是人类重要的健康问题。由于其高发病率和死亡率,据估计全球每年有170万人死亡。目前,辅助治疗和肾移植是最常见的治疗方法。最近的研究表明,急性肾损伤的发病机理与细胞内过量的活性氧和活性氮物种相关。此前,一些小分子药物,例如,氨磷汀和乙酰半胱氨酸,已经被证明可以作为抗氧化剂,消除活性氧,以此来缓解急性肾损伤。然而,小分子药物具有较低的利用率,较大的毒副作用以及有限的疗效。这些都阻碍了他们的临床应用。但是,抗氧化剂的成功发展为急性肾损伤未来的治疗提供了充分的基础。
发明内容
发明人研究发现,相较于传统蛋白酶,纳米酶具有成本低、催化性质可调、可大规模制备等明显优势。同时,纳米酶,尤其是美国食品和药物管理局批准的普鲁士蓝等材料具有广谱的活性氧和活性氮的清除能力。此外,纳米材料具有独特的物理化学性质,这使得它们可作为临床或预临床成像手段的造影剂。更重要的是,超小的纳米颗粒可以通过肾脏进行代谢,这就为急性肾损伤的治疗提供了可能。
基于此,本发明开发了利用纳米酶用于急性肾损伤的治疗。
具体地,本发明提供一种用于急性肾损伤的纳米酶诊疗剂及其制备方法与应用,旨在解决现有的小分子药物利用率低、副作用大,难以用于急性肾损伤治疗的技术问题。
本发明第一方面,提供一种用于急性肾损伤的纳米酶诊疗剂,其中,包括:普鲁士蓝纳米颗粒,结合在所述普鲁士蓝纳米颗粒表面的表面配体。
本发明表面配体能够有效的稳定普鲁士蓝纳米颗粒,控制普鲁士蓝纳米颗粒具有很小的尺寸。并且它们都具有良好的水溶性和生物安全性,不易与血清内蛋白发生作用,有利于纳米酶诊疗剂在血液中的循环。
可选地,所述表面配体选自聚乙烯吡咯烷酮、壳聚糖、柠檬酸、聚乙二醇、聚氧乙烯聚氧丙烯醚嵌段共聚物等中的一种或多种,但不限于此。
可选地,所述表面配体为壳聚糖。
可选地,所述普鲁士蓝纳米颗粒和所述表面配体的质量比为1:(1-10)。
可选地,所述纳米酶诊疗剂为直径小于6nm的球形颗粒。
本发明第二方面,提供一种如上所述的纳米酶诊疗剂的制备方法,其中,包括步骤:将铁盐、铁氰化盐和表面配体混合于水中,搅拌并加热,得到混合溶液;将所述混合溶液进行分离洗涤,得到所述纳米酶诊疗剂。
可选地,所述铁盐与铁氰化盐的摩尔比为1:1。
可选地,所述搅拌并加热的时间为1-4小时,所述搅拌并加热的温度为25-60摄氏度。
本发明第三方面,提供一种如上所述的纳米酶诊疗剂在制备诊断和治疗急性肾损伤制剂中的应用。
本发明第四方面,提供一种如上所述的纳米酶诊疗剂作为核磁共振成像、光声成像技术的造影剂的应用。
有益效果:本发明纳米酶诊疗剂包括表面配体以及由所述表面配体保护的普鲁士蓝纳米颗粒,所述表面配体能够有效的稳定普鲁士蓝纳米颗粒,控制普鲁士蓝纳米颗粒具有很小的尺寸。本发明的纳米酶诊疗剂具有超小的尺寸,能够有效的富集于小鼠肾脏,能够清除肾小管内大量的活性氧或活性氮以缓解和治疗甘油或顺铂诱导的急性肾损伤,并且可作为核磁共振成像、光声成像技术的造影剂。另外,这些纳米酶诊疗剂具有良好的治疗效果,同时具有优异的生物相容性和生物安全性。
附图说明
图1为本发明具体的实施例中纳米酶诊疗剂的合成路线图;
图2为本发明具体的实施例中纳米酶诊疗剂的AFM图;
图3为本发明具体的实施例中纳米酶诊疗剂的XRD图;
图4为本发明具体的实施例中纳米酶诊疗剂羟基自由基清除率图;
图5为本发明具体的实施例中纳米酶诊疗剂超氧阴离子清除率图;
图6为本发明具体的实施例中纳米酶诊疗剂自由基清除率图;
图7为本发明具体的实施例中纳米酶诊疗剂氮自由基清除率图;
图8为本发明具体的实施例中纳米酶诊疗剂处理肾小管细胞(293T)存活率图;
图9为本发明具体的实施例中纳米酶诊疗剂在肾小管细胞(293T)中清除活性氧图;
图10为本发明具体的实施例中纳米酶诊疗剂在肾小管细胞(293T)中清除一氧化氮图;
图11为本发明具体的实施例中纳米酶诊疗剂在肾小管细胞(293T)中清除过氧亚硝酸盐图;
图12为本发明具体的实施例中纳米酶诊疗剂在不同时间小鼠肾脏光声成像变化图;
图13为本发明具体的实施例中纳米酶诊疗剂在不同时间小鼠肾脏核磁共振成像变化图;
图14为本发明具体的实施例中纳米酶诊疗剂不同治疗组小鼠血清中血尿素氮含量图;
图15为本发明具体的实施例中纳米酶诊疗剂不同治疗组小鼠血清中血肌酐含量图;
图16为本发明具体的实施例中注射纳米酶诊疗剂和磷酸缓冲液(对照)老鼠的体重随时间的变化图。
具体实施方式
本发明提供一种用于急性肾损伤的纳米酶诊疗剂及其制备方法与应用,为使本发明的目的、技术方案及效果更加清楚、明确,以下对本发明进一步详细说明。应当理解,此处所描述的具体实施例仅仅用以解释本发明,并不用于限定本发明。
本发明实施例提供一种用于急性肾损伤的纳米酶诊疗剂,其中,包括:普鲁士蓝纳米颗粒,结合在所述普鲁士蓝纳米颗粒表面的表面配体。
本发明实施例纳米酶诊疗剂包括表面配体以及由所述表面配体保护的普鲁士蓝纳米颗粒,所述表面配体能够有效的稳定普鲁士蓝纳米颗粒,控制普鲁士蓝纳米颗粒具有很小的尺寸,使得最终获得的纳米酶诊疗剂有超小的尺寸。本发明该纳米酶诊疗剂具有超小的尺寸,利于有效到达小鼠肾脏,通过清除肾小管内大量的活性氧或活性氮以缓解和治疗急性肾损伤,并且具有核磁共振成像、光声成像等特性。
需说明的是,本发明实施例不限于所述普鲁士蓝纳米颗粒,还可以是普鲁士绿纳米颗粒等,但不限于此。
在一种实施方式中,所述表面配体选自聚乙烯吡咯烷酮、壳聚糖、柠檬酸、聚乙二醇、聚氧乙烯聚氧丙烯醚嵌段共聚物(F127等)等中的一种或多种,但不限于此。这些表面配体能够有效的稳定纳米颗粒,控制纳米颗粒具有很小的尺寸。并且它们都具有良好的水溶性和生物安全性,不易与血清内蛋白发生作用,有利于纳米颗粒在血液中的循环。
在一种实施方式中,所述普鲁士蓝纳米颗粒和所述表面配体的质量比为1:(1-100),如1:50。该比例范围内得到的纳米酶诊疗剂具有良好的分散性和稳定性,并且具有很小的尺寸。
在一种实施方式中,所述纳米酶诊疗剂为直径小于6nm的球形颗粒。超小的纳米颗粒有利于到达小鼠肾脏,且超小的纳米颗粒有利于通过肾脏进行代谢。
本发明实施例提供一种如上所述纳米酶诊疗剂的制备方法,其中,包括步骤:将铁盐、铁氰化盐和表面配体混合于水中,搅拌并加热,得到混合溶液;将所述混合溶液进行分离洗涤,得到所述纳米酶诊疗剂。
在一种实施方式中,将所述混合溶液加入到丙酮中进行分离洗涤,即得到所述纳米酶诊疗剂。
在一种实施方式中,所述铁盐与铁氰化盐的摩尔比为1:1。
在一种实施方式中,所述表面配体为壳聚糖。以摩尔比计,铁盐:铁氰化盐:壳聚糖:水=1:1:50:1000。铁盐与铁氰化盐保证产生为普鲁士蓝纯品,大量壳聚糖表面配体能够很好的稳定形成的超小普鲁士蓝纳米颗粒,大量溶剂的水的使用可以保证材料良好的分散性。
在一种实施方式中,所述搅拌并加热的时间为1-4小时(如1小时)。
在一种实施方式中,所述搅拌并加热的温度为25-60摄氏度。
在一种实施方式中,所述铁盐选自氯化铁、氯化亚铁等中的一种或多种,但不限于此。
在一种实施方式中,所述铁氰化盐选自铁氰化钾、亚铁氰化钾等中的一种或多种,但不限于此。
一种本发明实施例所述的纳米酶诊疗剂在制备诊断和治疗急性肾损伤制剂中的应用。
一种本发明实施例所述的纳米酶诊疗剂作为核磁共振成像、光声成像技术的造影剂的应用。
下面通过具体的实施例对本发明的技术方案作进一步地说明。
实施例1:合成纳米酶诊疗剂
纳米酶诊疗剂合成:如图1所示,将铁氰化钾(1毫摩/升,20毫升)溶液加入到80毫升壳聚糖溶液(3毫克/毫升)中,然后搅拌并滴加氯化亚铁溶液(1毫摩/升,20毫升)。25℃条件下搅拌反应1小时。随后加入120mL丙酮。用8000rpm转数离心,得到的蓝色沉淀用丙酮洗涤数次,烘干得到最终产品。
图1为合成纳米酶诊疗剂的路线图,其中K3[Fe(CN)]6代表铁氰化钾,CS代表壳聚糖,FeCl2代表氯化亚铁。所述纳米酶诊疗剂中的壳聚糖表面配体能够很好地稳定普鲁士蓝纳米颗粒。
图2是合成的纳米酶诊疗剂的AFM图;图3是合成的纳米酶诊疗剂的XRD图;图2和图3表明纳米酶诊疗剂具有超小的尺寸。
实施例2:纳米酶诊疗剂清除各种活性氧/活性氮能力及纳米酶诊疗剂清除羟基自由基的能力
不同浓度纳米酶诊疗剂(0-100μg/mL)清除羟基自由基的效率是通过羟基自由基抗氧化能力(HORAC)试剂盒(Cell Biolabs,Inc.,USA)测定的。测试是按照制造商提供的方案进行的。
如图4所示,纳米酶诊疗剂能够有效的清除羟基自由基,并且具有浓度依赖的特性。
不同浓度纳米酶诊疗剂(0-100μg/mL)清除超氧阴离子的效率是通过SOD检测试剂盒(Sigma-Aldrich,USA)测定的。测试是按照制造商提供的方案进行的。
如图5所示,纳米酶诊疗剂能够有效的清除超氧阴离子,并且具有浓度依赖的特性。
纳米酶诊疗剂清除ABTS(2,2'-联氮双(3-乙基苯并噻唑啉-6-磺酸)二铵盐)自由基的测试
用ABTS自由基阳离子脱色法测定了纳米酶诊疗剂的自由基清除能力。ABTS(7mM)溶于水,加入2.45mM过硫酸钾反应12小时,可产生ABTS自由基阳离子(·ABTS+)。然后在734nm处测定纯·ABTS+溶液(AB)和不同浓度(0-50μg/mL)纳米酶诊疗剂与·ABTS+混合溶液的吸光度值。ABTS清除效率的计算公式为[(AB-AP)/AB]*100。所有的测量都是一式三次。
如图6所示,纳米酶诊疗剂能够有效的清除自由基,并且具有浓度依赖的特性。
纳米酶诊疗剂清除氮自由基(DPPH)
采用DPPH法评价纳米酶诊疗剂对活性氮清除活性。将不同浓度的纳米酶诊疗剂(200μg/mL)与40μM DPPH混合后记录其在550纳米处吸收光谱变化。
如图7所示,混合了纳米酶之后,DPPH在550纳米处的特征峰随时间明显下降,证明纳米酶诊疗剂能够有效的清除活性氮DPPH。
实施例3:纳米酶诊疗剂细胞毒性和通过清除各种活性氧/活性氮保护肾细胞采用标准的MTT法,评价纳米酶诊疗剂对293T肾胚胎细胞存活率的影响。
293T细胞以每孔1×104密度接种到96孔板中,并置于37度、5%CO2条件下培育12h。接着,吸出96孔板中的旧培养基,分别加入含有不同浓度纳米酶诊疗剂的培养基溶液。继续培养20h后,吸出96孔板中的旧培养基,在每个孔中加入100μLMTT的培养基溶液(0.8mg/mL,继续培养4h。吸出96孔板中的残余培养基,在每个孔中加入150μL DMSO溶液,轻轻摇晃后,在Synergy H1型酶标仪上检测每孔的OD值(检测波长为570nm),用如下公式计算细胞存活率。细胞存活率(cell viability)(%)=(样品的OD570值/空白OD570值)×100%。
如图8所示,合成的纳米酶诊疗剂对293T肾胚胎细胞的细胞存活率,在浓度达到最大使用浓度200μg/mL时,细胞依然保持80%以上的存活率。表明本实施例的纳米酶诊疗剂具有较低的细胞毒性。
以纳米酶诊疗剂为例,293T细胞提前4小时处理纳米酶诊疗剂(200μg/mL)后,加入含2mM过氧化氢的培养基。再分别使用活性氧(图9)、一氧化氮(图10)、过氧亚硝酸盐(图11)探针染色,洗涤之后使用激光共聚焦显微镜进行成像。如图9-11所示,与过氧化氢刺激后的细胞相比,预处理纳米酶诊疗剂细胞中的荧光明显减弱,接近于对照组细胞。这说明纳米酶诊疗剂能够有效清除细胞中活性氧/活性氮,进而保护细胞。
实施例4:纳米酶诊疗剂肾脏蓄积和核磁共振成像、光声成像所有的实验操作均按照临床中心动物保健和使用委员会通过的动物使用和保健制度。雌性无胸腺小白鼠(六周,20-25g),在小白鼠后腿肌肉注射8mL/kg 50%的甘油溶液建立老鼠急性肾衰竭模型(RM-AKI)。2小时后,注射纳米酶诊疗剂。
在不同的时间点取出小鼠肾脏,使用核磁共振成像仪和光声成像仪对小鼠肾脏进行成像。如图12-13所示,小鼠肾脏的光声信号(图12)和核磁共振成像(图13)都有所增强,其中在2小时时信号最强,说明纳米酶诊疗剂能够快速的到达小鼠肾脏。
实施例5:纳米酶诊疗剂治疗急性肾损伤和生物安全性评价
所有的实验操作均按照临床中心动物保健和使用委员会通过的动物使用和保健制度。雌性无胸腺小白鼠(六周,20-25g),在小白鼠后腿肌肉注射8mL/kg 50%的甘油溶液建立老鼠急性肾衰竭模型。2小时后,注射小分子药物氨磷汀或者纳米酶诊疗剂。此外,腹腔注射顺铂(20毫克/千克)构建顺铂诱导急性肾衰竭小鼠模型(CP-AKI),立刻静脉注射氨磷汀或者纳米酶诊疗剂。
小鼠随机分为8组:(1)健康鼠注射磷酸缓冲液;(2)健康鼠注射纳米酶诊疗剂;(3)甘油诱导的急性肾衰竭鼠注射磷酸缓冲液;(4)甘油诱导的急性肾衰竭鼠注射纳米酶诊疗剂;(5)甘油诱导的急性肾衰竭鼠注射氨磷汀;(6)顺铂诱导的急性肾衰竭鼠注射磷酸缓冲液;(7)顺铂诱导的急性肾衰竭鼠注射纳米酶诊疗剂(8)顺铂诱导的急性肾衰竭鼠注射与纳米酶诊疗剂等量的氨磷汀。健康鼠和甘油诱导的急性肾衰竭鼠24小时后安乐死小鼠,顺铂诱导急性肾衰竭鼠72小时安乐死小鼠取小鼠血液离心获得血清,测量肌酐和血尿素氮含量。注射使用磷酸缓冲液为100μL,纳米酶诊疗剂为100μg,氨磷汀为100μg。
如图14-15所示,健康鼠注射纳米酶诊疗剂的肌酐和血尿素氮含量没有明显变化。而注射纳米酶诊疗剂的急性肾衰竭小鼠肌酐和血尿素氮含量明显低于只注射磷酸缓冲液的小鼠,并接近健康鼠的水平。另一方面,高剂量的氨磷汀注射后也能获得与注射纳米酶诊疗剂相似的效果,而同等剂量的氨磷汀并不能有效的降低两个指标。这说明四种纳米酶诊疗剂能够有效的缓解和治疗急性肾衰竭,并具有比小分子药物氨磷汀更好的治疗效果。
此外,使用健康鼠注射磷酸缓冲液和纳米酶诊疗剂,记录小鼠一个月内的体重变化情况。如图16所示,与对照组相比,注射纳米酶诊疗剂的小鼠体重没有明显差异。
综上所述,本发明的纳米酶诊疗剂通过简单的合成方法,可大量制备出超小纳米颗粒,能够有效的清除各类活性氧/活性氮物种,具有广谱的活性氧/活性氮清除能力。并且对293T肾细胞的毒副作用较低,与细胞共培养24小时后细胞存活率均达到80%以上;同时它们可以通过清除细胞内多余的活性氧/活性氮来保护细胞免受过氧化氢刺激。借助纳米酶自身特殊的性质,可以通过核磁共振成像、光声成像手段来监测纳米酶在小鼠肾脏的有效累积。此外,纳米酶诊疗剂在甘油或顺铂诱导的急性肾衰竭小鼠显示出良好的治疗效果。更重要的是,纳米酶诊疗剂具有良好的生物相容性和生物安全性。
应当理解的是,本发明的应用不限于上述的举例,对本领域普通技术人员来说,可以根据上述说明加以改进或变换,所有这些改进和变换都应属于本发明所附权利要求的保护范围。
Claims (1)
1.一种纳米酶诊疗剂在制备诊断和治疗急性肾损伤制剂中的应用,其特征在于,所述纳米酶诊疗剂包括:普鲁士蓝纳米颗粒,结合在所述普鲁士蓝纳米颗粒表面的表面配体;
所述表面配体为壳聚糖;
所述纳米酶诊疗剂的制备方法,包括步骤:将铁盐、铁氰化盐和所述表面配体混合于水中,搅拌并加热,得到混合溶液;将所述混合溶液进行分离洗涤,得到所述纳米酶诊疗剂;
所述纳米酶诊疗剂能够清除活性氧、活性氮及羟基自由基;
所述普鲁士蓝纳米颗粒和所述表面配体的质量比为1:(1-10);
所述纳米酶诊疗剂为直径小于6nm的球形颗粒;
所述铁盐:铁氰化盐:表面配体:水的摩尔比为1:1:50:1000;
所述搅拌并加热的时间为1-4小时,所述搅拌并加热的温度为25-60摄氏度。
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202011328063.1A CN112516336B (zh) | 2020-11-24 | 2020-11-24 | 一种用于急性肾损伤的纳米酶诊疗剂及其制备方法与应用 |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202011328063.1A CN112516336B (zh) | 2020-11-24 | 2020-11-24 | 一种用于急性肾损伤的纳米酶诊疗剂及其制备方法与应用 |
Publications (2)
Publication Number | Publication Date |
---|---|
CN112516336A CN112516336A (zh) | 2021-03-19 |
CN112516336B true CN112516336B (zh) | 2023-09-26 |
Family
ID=74992934
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN202011328063.1A Active CN112516336B (zh) | 2020-11-24 | 2020-11-24 | 一种用于急性肾损伤的纳米酶诊疗剂及其制备方法与应用 |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN112516336B (zh) |
Families Citing this family (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN112972706B (zh) * | 2021-04-01 | 2023-07-14 | 中国药科大学 | 一种peg修饰的黑磷量子点在评价药源性急性肾损伤方面的应用 |
CN114681482B (zh) * | 2021-08-30 | 2023-05-05 | 深圳大学 | 一种纳米酶及其制备方法与应用 |
CN114272264A (zh) * | 2021-11-16 | 2022-04-05 | 上海市第十人民医院 | 一种普鲁士钙纳米颗粒在制备治疗和/或预防急性肾损伤疾病中的应用 |
CN114177339B (zh) * | 2021-11-25 | 2023-03-17 | 浙江理工大学 | 一种纳米酶和糖胺聚糖复合纳米纤维敷料的制备方法 |
CN115317516B (zh) * | 2022-08-29 | 2023-07-25 | 中南大学 | 一种超小抗氧化纳米点及其在急性肾损伤中的应用 |
Citations (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2006072962A1 (en) * | 2005-01-10 | 2006-07-13 | Secretary, Department Of Atomic Energy | Calcium potassium ferrocyanide, a prophylactic mixture comprising this compound and the use thereof for decorporation of radiocesium in subjects affected by nuclear radiation |
JP2006256954A (ja) * | 2005-02-17 | 2006-09-28 | National Institute Of Advanced Industrial & Technology | プルシアンブルー型金属錯体超微粒子、その分散液、及びそれらの製造方法 |
CN104096244A (zh) * | 2013-04-08 | 2014-10-15 | 北京大学 | 磁性普鲁士蓝纳米粒子用于癌症靶向诊疗的新应用 |
CN106581057A (zh) * | 2016-11-02 | 2017-04-26 | 中国科学院上海硅酸盐研究所 | 基于普鲁士蓝类似物的纳米诊疗剂及其制备方法和应用 |
CN110585448A (zh) * | 2019-08-23 | 2019-12-20 | 深圳大学 | 一种用于急性肾损伤的纳米诊疗剂及其制备方法与应用 |
WO2020175974A2 (ko) * | 2019-02-26 | 2020-09-03 | 한국세라믹기술원 | 활성산소 제거를 위한 프러시안 블루/키토산 나노입자 복합체 및 이의 용도 |
Family Cites Families (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP2675486A2 (en) * | 2011-02-15 | 2013-12-25 | Semmelweis Egyetem | Prussian blue based nanoparticle as multimodal imaging contrast material |
-
2020
- 2020-11-24 CN CN202011328063.1A patent/CN112516336B/zh active Active
Patent Citations (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2006072962A1 (en) * | 2005-01-10 | 2006-07-13 | Secretary, Department Of Atomic Energy | Calcium potassium ferrocyanide, a prophylactic mixture comprising this compound and the use thereof for decorporation of radiocesium in subjects affected by nuclear radiation |
JP2006256954A (ja) * | 2005-02-17 | 2006-09-28 | National Institute Of Advanced Industrial & Technology | プルシアンブルー型金属錯体超微粒子、その分散液、及びそれらの製造方法 |
CN104096244A (zh) * | 2013-04-08 | 2014-10-15 | 北京大学 | 磁性普鲁士蓝纳米粒子用于癌症靶向诊疗的新应用 |
CN106581057A (zh) * | 2016-11-02 | 2017-04-26 | 中国科学院上海硅酸盐研究所 | 基于普鲁士蓝类似物的纳米诊疗剂及其制备方法和应用 |
WO2020175974A2 (ko) * | 2019-02-26 | 2020-09-03 | 한국세라믹기술원 | 활성산소 제거를 위한 프러시안 블루/키토산 나노입자 복합체 및 이의 용도 |
CN110585448A (zh) * | 2019-08-23 | 2019-12-20 | 深圳大学 | 一种用于急性肾损伤的纳米诊疗剂及其制备方法与应用 |
Non-Patent Citations (2)
Title |
---|
"Chitosan stabilized Prussian blue nanoparticles for photothermally enhanced gene delivery";Xiao-Da Li et al.;《Colloids and Surfaces B: Biointerfaces》;20141130(第123期);摘要、第629页右栏第2段、第630页左栏第2、4段、第631页右栏第4段至第633页右栏第3段以及图1-2 * |
Xiao-Da Li et al.."Chitosan stabilized Prussian blue nanoparticles for photothermally enhanced gene delivery".《Colloids and Surfaces B: Biointerfaces》.2014,(第123期),第629-638页. * |
Also Published As
Publication number | Publication date |
---|---|
CN112516336A (zh) | 2021-03-19 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
CN112516336B (zh) | 一种用于急性肾损伤的纳米酶诊疗剂及其制备方法与应用 | |
CN112263686A (zh) | 一种用于急性肾损伤的纳米酶诊疗剂及其制备方法与应用 | |
Zhu et al. | An efficient tumor-inducible nanotheranostics for magnetic resonance imaging and enhanced photodynamic therapy | |
CN107412780B (zh) | 一种基于金纳米颗粒表面修饰氮杂环小分子的抗菌剂 | |
CN114377149B (zh) | 一种Mn基可降解MOF纳米反应器及其制备方法和应用 | |
Du et al. | Confined nanoparticles growth within hollow mesoporous nanoreactors for highly efficient MRI-guided photodynamic therapy | |
Pa̧zik et al. | Surface functionalization of the metal oxide nanoparticles with biologically active molecules containing phosphonate moieties. Case study of BaTiO3 | |
Zhang et al. | Synergistic ferroptosis-gemcitabine chemotherapy of the gemcitabine loaded carbonaceous nanozymes to enhance the treatment and magnetic resonance imaging monitoring of pancreatic cancer | |
Wang et al. | Advancements of Prussian blue-based nanoplatforms in biomedical fields: Progress and perspectives | |
Mehravi et al. | Acute toxicity evaluation of glycosylated Gd 3+-based silica nanoprobe | |
Mallik et al. | Porous Silica Nanospheres with a Confined Mono (aquated) Mn (II)-Complex: A Potential T 1–T 2 Dual Contrast Agent for Magnetic Resonance Imaging | |
Wan et al. | Counterion-induced antibiotic-based small-molecular micelles for methicillin-resistant Staphylococcus aureus infections | |
Yan et al. | A tumor-targeting and ROS-responsive iron-based T 1 magnetic resonance imaging contrast agent for highly specific tumor imaging | |
Nadaf et al. | Biogenic and biomimetic functionalized magnetic nanosystem: Synthesis, properties, and biomedical applications | |
JP6118351B2 (ja) | PEG置換α−ヒドロキシホスホネート外殻を有する超常磁性ナノ粒子 | |
JP4669837B2 (ja) | 金属ポルフィリン錯体包埋ニオソーム、その製造法およびこれを利用する医薬 | |
KR20150078375A (ko) | 철산화물 나노입자를 포함하는 철결핍증의 예방 또는 치료용 약학 조성물 | |
EP4371576A1 (en) | Acetylcysteine-stabilized gold nanoclusters for acute kidney injury, and preparation method therefor and use thereof | |
Sobhani et al. | Novel MR imaging nanoprobe for hepatocellular carcinoma detection based on manganese–zinc ferrite nanoparticles: In vitro and in vivo assessments | |
Li et al. | ROS-responsive EPO nanoparticles ameliorate ionizing radiation-induced hematopoietic injury | |
CN113549611B (zh) | 一种级联纳米酶及其制备方法与应用 | |
CN115400223A (zh) | 一种二茂铁和tlr7/8激动剂共连接纳米粒及其制备方法和应用 | |
CN110368359B (zh) | 一种基于支化聚乙烯亚胺合成的杂化纳米水凝胶及其制备和应用 | |
CN110585448B (zh) | 一种用于急性肾损伤的纳米诊疗剂及其制备方法与应用 | |
CN114681482B (zh) | 一种纳米酶及其制备方法与应用 |
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 |