CN114522181A - 氨基酸修饰的介孔聚多巴胺纳米粒子及其制备方法与应用 - Google Patents
氨基酸修饰的介孔聚多巴胺纳米粒子及其制备方法与应用 Download PDFInfo
- Publication number
- CN114522181A CN114522181A CN202210090303.1A CN202210090303A CN114522181A CN 114522181 A CN114522181 A CN 114522181A CN 202210090303 A CN202210090303 A CN 202210090303A CN 114522181 A CN114522181 A CN 114522181A
- Authority
- CN
- China
- Prior art keywords
- amino acid
- solution
- preparation
- amm
- modified mesoporous
- 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
- 239000002105 nanoparticle Substances 0.000 title claims abstract description 48
- 229920001690 polydopamine Polymers 0.000 title claims abstract description 28
- 150000001413 amino acids Chemical class 0.000 title claims abstract description 27
- 238000002360 preparation method Methods 0.000 title claims abstract description 19
- VYFYYTLLBUKUHU-UHFFFAOYSA-N dopamine Chemical compound NCCC1=CC=C(O)C(O)=C1 VYFYYTLLBUKUHU-UHFFFAOYSA-N 0.000 claims abstract description 18
- 238000000034 method Methods 0.000 claims abstract description 14
- 230000004054 inflammatory process Effects 0.000 claims abstract description 13
- 229960003638 dopamine Drugs 0.000 claims abstract description 9
- 239000000243 solution Substances 0.000 claims description 34
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 20
- 239000004721 Polyphenylene oxide Substances 0.000 claims description 18
- 229920000570 polyether Polymers 0.000 claims description 18
- 239000004475 Arginine Substances 0.000 claims description 17
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 claims description 17
- AUHZEENZYGFFBQ-UHFFFAOYSA-N 1,3,5-trimethylbenzene Chemical compound CC1=CC(C)=CC(C)=C1 AUHZEENZYGFFBQ-UHFFFAOYSA-N 0.000 claims description 12
- 238000009210 therapy by ultrasound Methods 0.000 claims description 10
- 206010061218 Inflammation Diseases 0.000 claims description 9
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 9
- 150000003254 radicals Chemical class 0.000 claims description 9
- 239000007864 aqueous solution Substances 0.000 claims description 8
- 229910052751 metal Chemical class 0.000 claims description 7
- 239000002184 metal Chemical class 0.000 claims description 7
- 239000003960 organic solvent Substances 0.000 claims description 7
- 150000003839 salts Chemical class 0.000 claims description 7
- 239000003814 drug Substances 0.000 claims description 6
- 239000011259 mixed solution Substances 0.000 claims description 6
- 238000005481 NMR spectroscopy Methods 0.000 claims description 4
- 230000002000 scavenging effect Effects 0.000 claims description 4
- 239000002405 nuclear magnetic resonance imaging agent Substances 0.000 claims description 3
- PWHULOQIROXLJO-UHFFFAOYSA-N Manganese Chemical group [Mn] PWHULOQIROXLJO-UHFFFAOYSA-N 0.000 claims description 2
- 230000002757 inflammatory effect Effects 0.000 abstract description 12
- 238000002595 magnetic resonance imaging Methods 0.000 abstract description 11
- 230000036542 oxidative stress Effects 0.000 abstract description 6
- 238000001727 in vivo Methods 0.000 abstract description 4
- 230000014759 maintenance of location Effects 0.000 abstract description 4
- 230000002035 prolonged effect Effects 0.000 abstract description 3
- 230000002829 reductive effect Effects 0.000 abstract description 3
- 230000003647 oxidation Effects 0.000 abstract description 2
- 238000007254 oxidation reaction Methods 0.000 abstract description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 26
- 239000002245 particle Substances 0.000 description 16
- 230000000694 effects Effects 0.000 description 13
- 238000003756 stirring Methods 0.000 description 12
- 230000000052 comparative effect Effects 0.000 description 9
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 8
- 238000009826 distribution Methods 0.000 description 8
- 238000002835 absorbance Methods 0.000 description 6
- 239000002872 contrast media Substances 0.000 description 6
- 239000011572 manganese Substances 0.000 description 6
- 239000002244 precipitate Substances 0.000 description 6
- YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 6
- 230000002292 Radical scavenging effect Effects 0.000 description 5
- 238000012512 characterization method Methods 0.000 description 5
- 238000010586 diagram Methods 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
- 229940099596 manganese sulfate Drugs 0.000 description 5
- 239000011702 manganese sulphate Substances 0.000 description 5
- 235000007079 manganese sulphate Nutrition 0.000 description 5
- SQQMAOCOWKFBNP-UHFFFAOYSA-L manganese(II) sulfate Chemical group [Mn+2].[O-]S([O-])(=O)=O SQQMAOCOWKFBNP-UHFFFAOYSA-L 0.000 description 5
- 229910052757 nitrogen Inorganic materials 0.000 description 5
- 229910021642 ultra pure water Inorganic materials 0.000 description 5
- 239000012498 ultrapure water Substances 0.000 description 5
- CTENFNNZBMHDDG-UHFFFAOYSA-N Dopamine hydrochloride Chemical compound Cl.NCCC1=CC=C(O)C(O)=C1 CTENFNNZBMHDDG-UHFFFAOYSA-N 0.000 description 4
- 230000005540 biological transmission Effects 0.000 description 4
- 238000005119 centrifugation Methods 0.000 description 4
- 229960001149 dopamine hydrochloride Drugs 0.000 description 4
- 229940079593 drug Drugs 0.000 description 4
- TUJKJAMUKRIRHC-UHFFFAOYSA-N hydroxyl Chemical compound [OH] TUJKJAMUKRIRHC-UHFFFAOYSA-N 0.000 description 4
- 238000003760 magnetic stirring Methods 0.000 description 4
- 229910052760 oxygen Inorganic materials 0.000 description 4
- 238000005406 washing Methods 0.000 description 4
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 238000003917 TEM image Methods 0.000 description 3
- 210000004027 cell Anatomy 0.000 description 3
- 238000009792 diffusion process Methods 0.000 description 3
- 238000004090 dissolution Methods 0.000 description 3
- 238000002296 dynamic light scattering Methods 0.000 description 3
- 239000001301 oxygen Substances 0.000 description 3
- -1 oxygen Radicals Chemical class 0.000 description 3
- FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 3
- 229960004889 salicylic acid Drugs 0.000 description 3
- 238000002336 sorption--desorption measurement Methods 0.000 description 3
- GLDQAMYCGOIJDV-UHFFFAOYSA-N 2,3-dihydroxybenzoic acid Chemical compound OC(=O)C1=CC=CC(O)=C1O GLDQAMYCGOIJDV-UHFFFAOYSA-N 0.000 description 2
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- 102000016938 Catalase Human genes 0.000 description 2
- 108010053835 Catalase Proteins 0.000 description 2
- 102000006587 Glutathione peroxidase Human genes 0.000 description 2
- 108700016172 Glutathione peroxidases Proteins 0.000 description 2
- 102000019197 Superoxide Dismutase Human genes 0.000 description 2
- 108010012715 Superoxide dismutase Proteins 0.000 description 2
- 239000007983 Tris buffer Substances 0.000 description 2
- 238000010521 absorption reaction Methods 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- 229910052782 aluminium Inorganic materials 0.000 description 2
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 2
- 230000003110 anti-inflammatory effect Effects 0.000 description 2
- 239000003963 antioxidant agent Substances 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 239000011888 foil Substances 0.000 description 2
- 230000007760 free radical scavenging Effects 0.000 description 2
- 238000003384 imaging method Methods 0.000 description 2
- 210000004969 inflammatory cell Anatomy 0.000 description 2
- 230000005764 inhibitory process Effects 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 230000007246 mechanism Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 150000002831 nitrogen free-radicals Chemical class 0.000 description 2
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen(.) Chemical compound [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 239000000523 sample Substances 0.000 description 2
- 239000012488 sample solution Substances 0.000 description 2
- 238000006467 substitution reaction Methods 0.000 description 2
- 230000008685 targeting Effects 0.000 description 2
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 2
- 229940082044 2,3-dihydroxybenzoic acid Drugs 0.000 description 1
- 102000008186 Collagen Human genes 0.000 description 1
- 108010035532 Collagen Proteins 0.000 description 1
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
- 208000001034 Frostbite Diseases 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- 208000022559 Inflammatory bowel disease Diseases 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
- YJPIGAIKUZMOQA-UHFFFAOYSA-N Melatonin Natural products COC1=CC=C2N(C(C)=O)C=C(CCN)C2=C1 YJPIGAIKUZMOQA-UHFFFAOYSA-N 0.000 description 1
- 102100031455 NAD-dependent protein deacetylase sirtuin-1 Human genes 0.000 description 1
- 108010041191 Sirtuin 1 Proteins 0.000 description 1
- 229960004308 acetylcysteine Drugs 0.000 description 1
- 230000002776 aggregation Effects 0.000 description 1
- 238000004220 aggregation Methods 0.000 description 1
- 229940121363 anti-inflammatory agent Drugs 0.000 description 1
- 239000002260 anti-inflammatory agent Substances 0.000 description 1
- 229940124599 anti-inflammatory drug Drugs 0.000 description 1
- 229940037157 anticorticosteroids Drugs 0.000 description 1
- 230000003078 antioxidant effect Effects 0.000 description 1
- 208000006673 asthma Diseases 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000002902 bimodal effect Effects 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 230000023852 carbohydrate metabolic process Effects 0.000 description 1
- 235000021256 carbohydrate metabolism Nutrition 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 229920001436 collagen Polymers 0.000 description 1
- 229910052802 copper Inorganic materials 0.000 description 1
- 239000010949 copper Substances 0.000 description 1
- 239000003246 corticosteroid Substances 0.000 description 1
- 230000003013 cytotoxicity Effects 0.000 description 1
- 231100000135 cytotoxicity Toxicity 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 239000008367 deionised water Substances 0.000 description 1
- 229910021641 deionized water Inorganic materials 0.000 description 1
- 238000003795 desorption Methods 0.000 description 1
- MGJZITXUQXWAKY-UHFFFAOYSA-N diphenyl-(2,4,6-trinitrophenyl)iminoazanium Chemical compound [O-][N+](=O)C1=CC([N+](=O)[O-])=CC([N+]([O-])=O)=C1N=[N+](C=1C=CC=CC=1)C1=CC=CC=C1 MGJZITXUQXWAKY-UHFFFAOYSA-N 0.000 description 1
- 238000007599 discharging Methods 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 238000002651 drug therapy Methods 0.000 description 1
- 238000002149 energy-dispersive X-ray emission spectroscopy Methods 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 230000028993 immune response Effects 0.000 description 1
- 208000027866 inflammatory disease Diseases 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- 210000000265 leukocyte Anatomy 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 210000002540 macrophage Anatomy 0.000 description 1
- 150000002696 manganese Chemical class 0.000 description 1
- 229910052748 manganese Inorganic materials 0.000 description 1
- FWHZQBMZKQZFJG-UHFFFAOYSA-N manganese hydrochloride Chemical compound Cl.[Mn] FWHZQBMZKQZFJG-UHFFFAOYSA-N 0.000 description 1
- MIVBAHRSNUNMPP-UHFFFAOYSA-N manganese(2+);dinitrate Chemical compound [Mn+2].[O-][N+]([O-])=O.[O-][N+]([O-])=O MIVBAHRSNUNMPP-UHFFFAOYSA-N 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- DRLFMBDRBRZALE-UHFFFAOYSA-N melatonin Chemical compound COC1=CC=C2NC=C(CCNC(C)=O)C2=C1 DRLFMBDRBRZALE-UHFFFAOYSA-N 0.000 description 1
- 229960003987 melatonin Drugs 0.000 description 1
- FYFFGSSZFBZTAH-UHFFFAOYSA-N methylaminomethanetriol Chemical compound CNC(O)(O)O FYFFGSSZFBZTAH-UHFFFAOYSA-N 0.000 description 1
- 230000004770 neurodegeneration Effects 0.000 description 1
- 208000015122 neurodegenerative disease Diseases 0.000 description 1
- 238000002429 nitrogen sorption measurement Methods 0.000 description 1
- 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 description 1
- 230000005408 paramagnetism Effects 0.000 description 1
- 244000052769 pathogen Species 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 230000035699 permeability Effects 0.000 description 1
- 239000011148 porous material Substances 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 230000005855 radiation Effects 0.000 description 1
- 239000002516 radical scavenger Substances 0.000 description 1
- 238000011552 rat model Methods 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000000717 retained effect Effects 0.000 description 1
- 206010039073 rheumatoid arthritis Diseases 0.000 description 1
- 238000001878 scanning electron micrograph Methods 0.000 description 1
- 238000004626 scanning electron microscopy Methods 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 150000003384 small molecules Chemical class 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 238000004627 transmission electron microscopy Methods 0.000 description 1
- 230000008733 trauma Effects 0.000 description 1
- 238000001132 ultrasonic dispersion Methods 0.000 description 1
Images
Classifications
-
- 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
- A61K31/74—Synthetic polymeric materials
- A61K31/785—Polymers containing nitrogen
-
- 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
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
- A61K31/197—Carboxylic acids, e.g. valproic acid having an amino group the amino and the carboxyl groups being attached to the same acyclic carbon chain, e.g. gamma-aminobutyric acid [GABA], beta-alanine, epsilon-aminocaproic acid or pantothenic acid
- A61K31/198—Alpha-amino acids, e.g. alanine or edetic acid [EDTA]
-
- 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
- A61K49/126—Linear polymers, e.g. dextran, inulin, PEG
-
- 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
- A61K49/1857—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 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. PLGA
-
- 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
- A61K9/5146—Organic macromolecular compounds; Dendrimers obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, polyamines, polyanhydrides
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P39/00—General protective or antinoxious agents
- A61P39/06—Free radical scavengers or antioxidants
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B82—NANOTECHNOLOGY
- B82Y—SPECIFIC USES OR APPLICATIONS OF NANOSTRUCTURES; MEASUREMENT OR ANALYSIS OF NANOSTRUCTURES; MANUFACTURE OR TREATMENT OF NANOSTRUCTURES
- B82Y15/00—Nanotechnology for interacting, sensing or actuating, e.g. quantum dots as markers in protein assays or molecular motors
-
- 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)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Nanotechnology (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Epidemiology (AREA)
- Molecular Biology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Radiology & Medical Imaging (AREA)
- Crystallography & Structural Chemistry (AREA)
- General Chemical & Material Sciences (AREA)
- Physics & Mathematics (AREA)
- Toxicology (AREA)
- Rheumatology (AREA)
- Immunology (AREA)
- Biochemistry (AREA)
- Pain & Pain Management (AREA)
- Biomedical Technology (AREA)
- Optics & Photonics (AREA)
- Biophysics (AREA)
- Biotechnology (AREA)
- General Engineering & Computer Science (AREA)
- Medical Informatics (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
Abstract
本发明属于生物医药技术领域,具体涉及一种氨基酸修饰的介孔聚多巴胺纳米粒子及其制备方法与应用。本发明的纳米粒子采用在多巴胺中掺杂碱性氨基酸的方法制备得到。所得纳米粒子的结构为介孔球形结构,能有效增加纳米粒子的比表面积,延长在体内的保留时间;掺杂碱性氨基酸后,其抗氧化能力显著提高,可以有效降低炎症组织内氧化应激水平,减缓炎症进程;除此之外,本发明制备得到的纳米粒子还具有T1‑T2双模磁共振成像的功能,可用于炎症组织的磁共振成像。
Description
技术领域
本发明属于生物医药技术领域。更具体地,涉及一种氨基酸修饰的介孔聚多巴胺纳米粒子及其制备方法与应用。
背景技术
炎症是机体对诸多病原体、化学刺激、身体创伤、受损细胞、烧伤、辐射和冻伤等有害刺激的一种基本免疫应答。然而,炎症的持续发展可能引发多种疾病,如哮喘、炎性肠病、类风湿性关节炎和神经退行性疾病等,这些疾病往往难以治愈,是目前研究的重点和难点。当前炎症的治疗方法主要是药物治疗,包括服用非甾体类抗炎药、皮质类固醇等,通过减少炎症细胞(如巨噬细胞、白细胞等)聚集、抑制炎性因子释放等作用缓解炎症,但小分子药物缺乏靶向性,需长期频繁用药以达到治疗效果,因此具有较大副作用,增加患者负担。
近年来有研究表明,除直接抑制炎性因子释放以外,还可以通过降低炎症细胞内的氧化应激水平减缓炎症进程。在炎症患者体内,抗氧化剂机制(包括超氧化物歧化酶(Superoxide dismutase,SOD)、过氧化氢酶(catalase,CAT)和谷胱甘肽过氧化酶(glutathione peroxidise,GPX))的调节被放松,氧自由基(Reactive oxygen species,ROS)和氮自由基(Reactive nitrogen species,RNS)产生过量,导致氧化应激升高,从而引起DNA、脂质和蛋白质损伤以及产生细胞毒性,对炎症病情发展的多个阶段有促进作用。因此,抑制相关细胞中的ROS和RNS有望成为炎症治疗的有效手段。目前报道的抗氧化剂大多为小分子材料,如褪黑激素和N-乙酰半胱氨酸等,虽然具有抗炎功效,(Lim,H.D.;Kim,Y.S.;Ko,S.H.,Cytoprotective and anti-inflammatory effects of melatonin inhydrogen peroxide-stimulated CHON-001human chondrocyte cell line and rabbitmodel of osteoarthritis via the SIRT1 pathway.J Pineal Res 2012,53(3),225-237.),但小分子的分子量小,在体内循环的半衰期短、作用时间短、易通过循环排出体内的问题,除此之外,小分子的尺寸达不到EPR效应,因此,还存在靶向性差的问题,导致治疗效果并不理想。
发明内容
本发明要解决的技术问题是克服现有抗炎药物靶向性差,在体内循环的半衰期短、作用时间短、易通过循环排出体内,炎症治疗效果不理想的缺陷和不足,提供一种氨基酸修饰的介孔聚多巴胺纳米粒子的制备方法,该制备方法所得氨基酸修饰的介孔聚多巴胺纳米粒子在人体内保留时间较长,能同时具有治疗炎症与核磁共振成像的功能。
本发明的目的是提供一种氨基酸修饰的介孔聚多巴胺纳米粒子。
本发明的另一目的是提供一种氨基酸修饰的介孔聚多巴胺纳米粒子在制备治疗炎症药物中的应用。
本发明的另一目的是提供一种氨基酸修饰的介孔聚多巴胺纳米粒子在制备核磁共振造影剂中的应用。
本发明的上述目的通过以下技术方案实现:
一种氨基酸修饰的介孔聚多巴胺纳米粒子的制备方法,包括如下步骤:
将多巴胺、金属盐溶解于水中避光反应完全得溶液a;将嵌段式聚醚溶解于水、有机溶剂与溶液a的混合溶液中,滴加1,3,5-三甲苯超声至溶液变色,再滴加碱性氨基酸水溶液反应完全,后处理即得。
优选地,所述金属盐为锰盐。
具体的,所述锰盐为硫酸锰、硝酸锰或盐酸锰。
优选地,所述嵌段式聚醚为嵌段式聚醚F-127或嵌段式聚醚F-68。
优选地,所述碱性氨基酸为精氨酸。
优选地,所述多巴胺、金属盐、嵌段式聚醚与碱性氨基酸的质量比为(20~40):1:(100~130):(1~5)。
更优选地,所述多巴胺、金属盐、嵌段式聚醚与碱性氨基酸的质量比为(20~40):1:(100~130):(2~3)。
优选地,所述水、有机溶剂与溶液a的体积比为(10~30):(10~30):1。
更优选地,所述水、有机溶剂与溶液a的体积比为20:20:1。
优选地,所述有机溶剂为乙醇、丙酮或甲醇中的一种或多种。
本发明进一步保护一种氨基酸修饰的介孔聚多巴胺纳米粒子。
优选地,所述氨基酸修饰的介孔聚多巴胺纳米粒子的粒径为110~240nm。
优选地,所述氨基酸修饰的介孔聚多巴胺纳米粒子的比表面积为20~40m2/gnm。
与正常组织相比,当纳米粒子的粒径在200nm左右时,可以通过高通透性和滞留效应(EPR效应)靶向进入炎症组织并长期滞留,有效提高纳米粒子在炎症组织内的保留时间。
本发明进一步保护一种氨基酸修饰的介孔聚多巴胺纳米粒子在制备治疗炎症药物中的应用。
优选地,所述氨基酸修饰的介孔聚多巴胺纳米粒子用于清除自由基。
本发明创造性的在纳米粒子合成过程中掺杂碱性氨基酸,破坏多巴胺中多巴胺低聚物的致密微观结构,形成弱聚集体,使自由基具有较强的可及性,从而增强聚多巴胺纳米粒子的自由基清除性能,达到降低炎症组织内的氧化应激水平。
优选地,所述自由基包括氮自由基、氧自由基。
更优选地,所述氮自由基主要为1.1-二苯基-2-苦肼基(DPPH)自由基,所述氧自由基主要为羟基自由基。
本发明进一步保护一种氨基酸修饰的介孔聚多巴胺纳米粒子在制备核磁共振造影剂中的应用。
Mn2+具有顺磁性,能够缩短周围组织的T1弛豫时间,在T1W1上呈现高信号,而介孔结构所具有的几何约束作用是一种通过调整内球和外球机制以提高弛豫性的有效策略。具体而言,介孔结构可以使造影剂自由旋转,并使周围水分子的扩散受限,从而显著增加造影剂的旋转相关时间(τR)和水分子的扩散相关时间(τD),进而同时增强T1和T2造影效果。介孔结构缩短了T2弛豫时间、增加水分子在中孔内的扩散速率增强T1弛豫性,使得本发明制备得到的纳米粒子具有T1 T2造影效果。
本发明具有以下有益效果:
本发明的纳米粒子采用在多巴胺中掺杂碱性氨基酸的方法制备得到。所得纳米粒子的结构为介孔球形结构,能有效增加纳米粒子的比表面积,延长在体内的保留时间;掺杂碱性氨基酸后,其抗氧化能力显著提高,可以有效降低炎症组织内氧化应激水平,减缓炎症进程;除此之外,本发明制备得到的纳米粒子还具有T1-T2双模磁共振成像的功能,可用于炎症组织的磁共振成像。
附图说明
图1为本发明实施例1~3制备得到的氨基酸修饰的介孔聚多巴胺纳米粒子的紫外吸收图。
图2为对比例1制备得到的MM与实施例1制备得到的AMM-9的透射电镜图;图2A为对比例1制备得到MM的透射电镜图;图2B为实施例1制备得到AMM-9的透射电镜图。
图3为对比例1制备得到的MM与实施例1制备得到的AMM-9的粒径分布图;图3A为对比例1制备得到MM的粒径分布图;图3B为实施例1制备得到AMM-9的粒径分布图。
图4为实施例1制备得到的AMM-9的扫描电镜元素分布图。
图5为实施例1制备得到的AMM-9的氮气吸附/脱附曲线;图5A为AMM-9的氮气吸脱附等温线;图5B为AMM-9的孔径分布图。
图6为对比例1制备得到的MM与实施例1制备得到的AMM-9的DPPH自由基清除能力图。
图7为对比例1制备得到的MM与实施例1制备得到的AMM-9的羟基自由基清除能力图。
图8为实施例1制备得到的AMM-9在3.0T场强下成像效果以及弛豫速率与AMM-9浓度的关系;图8A为AMM-9的T1和T2 MRI图像;图8B为纵向弛豫率与AMM-9浓度之间的线性拟合图;图8C为横向弛豫率与AMM-9浓度之间的线性拟合图。
图9为实施例1制备得到的AMM-9在7.0T场强下成像效果以及弛豫速率与载体浓度的关系;图9A为T1 MRI图像;图9B为T2 MRI图像;图9C为纵向弛豫率与AMM-9浓度之间的线性拟合图;图9D为横向弛豫率与AMM-9浓度之间的线性拟合图。
具体实施方式
以下结合说明书附图和具体实施例来进一步说明本发明,但实施例并不对本发明做任何形式的限定。除非特别说明,本发明采用的试剂、方法和设备为本技术领域常规试剂、方法和设备。
除非特别说明,以下实施例所用试剂和材料均为市购。
实施例1氨基酸修饰的介孔聚多巴胺纳米粒子Arg-Mn-MPDA-9(AMM-9)的制备
将90mg盐酸多巴胺、3mg水合硫酸锰溶解于3mL超纯水中,在180rpm转速下避光搅拌24h,得溶液a;将0.36g嵌段式聚醚F-127(F-127)溶于6mL水、6mL乙醇、0.3mL溶液a的混合溶液中搅拌20min充分溶解,然后边超声边滴加300μL 1,3,5-三甲苯(TMB),超声4min至溶液呈乳白色后,在180rpm磁力搅拌边搅拌边滴加9mg/mL精氨酸水溶液(1mL),搅拌6h后分装至离心管离心,将沉淀用乙醇洗涤一次、水洗涤两次后收集得AMM-9。
实施例2氨基酸修饰的介孔聚多巴胺纳米粒子Arg-Mn-MPDA-6(AMM-6)的制备
将90mg盐酸多巴胺、3mg水合硫酸锰溶解于3mL超纯水中,在180rpm转速下避光搅拌24h,得溶液a;将0.36g嵌段式聚醚F-127(F-127)溶于6mL水、6mL乙醇、0.3mL溶液a的混合溶液中搅拌20min充分溶解,然后边超声边滴加300μL 1,3,5-三甲苯(TMB),超声4min至溶液呈乳白色后,在180rpm磁力搅拌边搅拌边滴加6mg/mL精氨酸水溶液(1mL),搅拌6h后分装至离心管离心,将沉淀用乙醇洗涤一次、水洗涤两次后收集得AMM-6。
与实施例1的区别在于,本实施例中的精氨酸水溶液浓度为6mg/mL。
实施例3氨基酸修饰的介孔聚多巴胺纳米粒子Arg-Mn-MPDA-12(AMM-12)的制备
将90mg盐酸多巴胺、3mg水合硫酸锰溶解于3mL超纯水中,在180rpm转速下避光搅拌24h,得溶液a;将0.36g嵌段式聚醚F-127(F-127)溶于6mL水、6mL乙醇、0.3mL溶液a的混合溶液中搅拌20min充分溶解,然后边超声边滴加300μL 1,3,5-三甲苯(TMB),超声4min至溶液呈乳白色后,在180rpm磁力搅拌边搅拌边滴加12mg/mL精氨酸水溶液(1mL),搅拌6h后分装至离心管离心,将沉淀用乙醇洗涤一次、水洗涤两次后收集得AMM-12。
与实施例1的区别在于,本实施例中的精氨酸水溶液浓度为12mg/mL。对比例1介孔聚多巴胺纳米粒子Mn-MPDA(MM)的制备
将90mg盐酸多巴胺、3mg水合硫酸锰溶解于3mL超纯水中,在180rpm转速下避光搅拌24h,得溶液a;将0.36g嵌段式聚醚F-127(F-127)溶于6mL水、6mL乙醇、0.3mL溶液a的混合溶液中搅拌20min充分溶解,然后边超声边滴加300μL 1,3,5-三甲苯(TMB),超声4min至溶液呈乳白色,在180rpm磁力搅拌下逐滴加入1mL浓度为9mg/mL的三羟甲基氨基甲烷(Tris)水溶液,搅拌6h后分装至离心管离心,将沉淀用乙醇洗涤一次、水洗涤两次后收集得掺杂锰的介孔聚多巴胺纳米粒子MM。
与实施例1的区别在于,将实施例1中浓度为9mg/mL的精氨酸水溶液替换成9mg/mL的Tris水溶液。
实施例4紫外分光光度计表征
将实施例制备得到的AMM-9、AMM-12、AMM-6用紫外分光光度计进行检测其吸光度。如图1所示,从紫外吸光度值可知,AMM-9精氨酸的相对掺杂量最多。
实施例5透射电子显微镜表征
将对比例1制备得到的MM与实施例1制备得到的AMM-9配制成50μg/mL的样品溶液,充分超声分散后,取10μL滴于碳支持膜铜网的正面,置于干燥器中室温条件下自然风干后于120KV电压条件下,使用透射电子显微镜(FEI,Tecnai G2 Spirit)观察MM、AMM-9的微观形态。
如图2所示,制得的MM(图2A)、AMM-9(图2B)均为球形,粒径均一,MM的透射电镜粒径为218.5nm,AMM-9的透射电镜粒径为225.6nm,呈现均匀分布的介孔结构,且精氨酸的掺杂对介孔球状结构没有明显的影响。
实施例6动态光散射表征
将对比例1制备得到的MM与实施例1制备得到的AMM-9在超纯水中重悬,稀释至50μg/mL后超声均匀,利用动态光散射法检测纳米粒子样品的水合粒径。
如图3所示,MM(图3A)和AMM-9(图3B)纳米粒子粒径分布范围较窄,表明粒径比较均一。MM的水合粒径约为224.7nm,AMM-9的水合粒径约为233.3nm,透射电镜与动态光散射法测量结果基本相同。
实施例7扫描电镜元素分布表征
将实施例1制备得到的AMM-9配制成50μg/mL的乙醇溶液,取少量滴于铝箔上,晾干后置于G500高分辨场发射扫描电镜(Gemini 500,Zeiss/Bruker)下观察粒子形貌,以及元素的分布。如图4所示,可以直观地观察到AMM-9纳米粒子为粒径均匀的圆球形,通过SEM中附带的EDS分析得到AMM-9纳米粒子的元素映射图,可以观察到C、O、N、Mn各元素的均匀分布,表明Mn元素和精氨酸(含N)均匀的掺杂在了介孔聚多巴胺纳米粒子(AMM)纳米粒子的内部。
实施例8氮气/吸脱附表征
将实施例1制备得到的AMM-9真空干燥,获得100mg AMM-9样品,用仪器测定氮气吸附/脱附曲线。如图5所示,利用BJH法计算出AMM-9纳米粒子的比表面积为30.8m2/g(图5A),孔径大小约为6.3nm(图5B)。
实施例9DPPH自由基清除实验
DPPH在有机溶剂中是一种稳定的氮自由基,当存在自由基清除剂时,DPPH的单电子被捕获,使其颜色变浅,最大吸收波长处的吸光度降低,因此选择它来评估自由基清除能力。将2mL DPPH/乙醇溶液(0.1mM)分别与20μL AMM-9溶液(1mg/mL)与MM溶液(1mg/mL)混合,测量20分钟内517nm处的吸光度,评估清除活性。如图6所示,在同等条件下,添加精氨酸的AMM-9组DPPH的清除率明显高于MM组,证明精氨酸的掺杂能够促进自由基的清除,提高清自由基除率。
实施例10羟基自由基清除实验
水杨酸可以与芬顿反应产生的·OH反应生成2,3-二羟基苯甲酸,在510nm处有特殊的吸光度,因此水杨酸法可以用于检测·OH的含量,评估纳米粒子的·OH清除能力。在离心管中加入适量去离子水、15mM水杨酸/乙醇溶液、15mM FeCl2、20mM H2O2和100μg/mL AMM-9或MM,置于37℃水浴中反应30分钟后,以不含H2O2的溶液为背景,检测溶液在510nm处的吸光度。如图7所示,在同等条件下,添加精氨酸的AMM-9组羟基自由基清除率明显高于MM组,进一步证明精氨酸的掺杂能够促进自由基的清除,显著提高自由基清除率。
实施例11磁共振成像(MRI)
将实施例1制备得到的AMM-9配制成不同浓度的溶液(Mn摩尔浓度为0,0.03,0.06,0.09,0.12,0.15,0.18,0.21,0.24mM),在3.0T核磁共振成像仪下进行扫描,图8A中的T1和T2磁共振图像显示,随着Mn浓度的升高,T1加权信号逐渐降低、T2加权信号逐渐升高,即造影效果逐渐增强。图8B和8C中线性拟合结果显示,AMM-9在3.0T场强下纵向弛豫速率(r1)和横向弛豫率(r2)分别为59.93mM-1S-1和61.59mM-1S-1,说明AMM-9可作为T1-T2双模造影剂用于磁共振成像。
将实施例1制备得到的AMM-9配制成不同浓度的溶液(Mn摩尔浓度为0,0.36,0.40,0.44,0.48,0.52,0.54,0.60mM),在7.0T核磁共振成像仪下进行扫描。图9A和图9B中T1和T2的磁共振图像显示,随着Mn浓度的升高,T1图像逐渐变亮;T2图像逐渐变暗,造影效果显著。图9C和图9D中线性拟合结果显示,AMM-9在7.0T场强下纵向弛豫速率(r1)和横向弛豫率(r2)分别为5.643mM-1S-1和56.96mM-1S-1。7T磁场的r1值明显小于3T磁场的r1值,这是由于在超高场(7T)下T2效应较强,可能会干扰T1造影剂的弛豫过程,从而显著降低T1信号。以上结果说明AMM-9可作为T1-T2双模造影剂用于超高场磁共振成像。
综合实施例1-11可见,本发明制备得到的AMM粒径均一,呈现均匀分布的介孔球形结构,比表面积大;精氨酸的掺杂量高,使其具有良好的自由基清除能力,可以有效降低炎症组织内氧化应激水平,减缓炎症进程;还可同时作为T1和T2的造影剂用于炎症组织的磁共振成像。
上述实施例为本发明较佳的实施方式,但本发明的实施方式并不受上述实施例的限制,其他的任何未背离本发明的精神实质与原理下所作的改变、修饰、替代、组合、简化,均应为等效的置换方式,都包含在本发明的保护范围之内。
Claims (10)
1.一种氨基酸修饰的介孔聚多巴胺纳米粒子的制备方法,其特征在于,包括如下步骤:
将多巴胺、金属盐溶解于水中避光反应完全得溶液a;将嵌段式聚醚溶解于水、有机溶剂与溶液a的混合溶液中,滴加1,3,5-三甲苯超声至溶液变色,再滴加碱性氨基酸水溶液反应完全,后处理即得。
2.根据权利要求1所述制备方法,其特征在于,所述金属盐为锰盐。
3.根据权利要求1所述制备方法,其特征在于,所述嵌段式聚醚为嵌段式聚醚F-127或嵌段式聚醚F-68。
4.根据权利要求1所述制备方法,其特征在于,所述碱性氨基酸为精氨酸。
5.根据权利要求1所述制备方法,其特征在于,所述多巴胺、金属盐、嵌段式聚醚与碱性氨基酸的质量比为(20~40):1:(100~130):(1~5)。
6.根据权利要求1所述制备方法,其特征在于,所述水、有机溶剂与溶液a的体积比为(10~30):(10~30):1。
7.权利要求1~6任一所述制备方法制备得到的氨基酸修饰的介孔聚多巴胺纳米粒子。
8.权利要求7所述氨基酸修饰的介孔聚多巴胺纳米粒子在制备治疗炎症药物中的应用。
9.根据权利要求8所述应用,其特征在于,所述氨基酸修饰的介孔聚多巴胺纳米粒子用于清除自由基。
10.权利要求7所述氨基酸修饰的介孔聚多巴胺纳米粒子在制备核磁共振造影剂中的应用。
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202210090303.1A CN114522181A (zh) | 2022-01-25 | 2022-01-25 | 氨基酸修饰的介孔聚多巴胺纳米粒子及其制备方法与应用 |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202210090303.1A CN114522181A (zh) | 2022-01-25 | 2022-01-25 | 氨基酸修饰的介孔聚多巴胺纳米粒子及其制备方法与应用 |
Publications (1)
Publication Number | Publication Date |
---|---|
CN114522181A true CN114522181A (zh) | 2022-05-24 |
Family
ID=81622163
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN202210090303.1A Pending CN114522181A (zh) | 2022-01-25 | 2022-01-25 | 氨基酸修饰的介孔聚多巴胺纳米粒子及其制备方法与应用 |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN114522181A (zh) |
Citations (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN108434462A (zh) * | 2018-03-13 | 2018-08-24 | 中山大学 | 一种介孔聚多巴胺负载羰基锰的多功能纳米诊疗剂及其制备方法与应用 |
CN109276721A (zh) * | 2018-09-19 | 2019-01-29 | 中山大学 | 一种靶向介孔聚多巴胺多功能纳米诊疗剂及其制备方法与应用 |
CN110804180A (zh) * | 2019-10-28 | 2020-02-18 | 长春理工大学 | 聚多巴胺纳米片的制备方法 |
CN111110652A (zh) * | 2020-01-06 | 2020-05-08 | 重庆医科大学 | 一种载药透明质酸聚多巴胺包覆介孔聚多巴胺纳米粒及其制备方法 |
CN112603910A (zh) * | 2020-12-31 | 2021-04-06 | 淮阴工学院 | 介孔聚多巴胺载花青素纳米粒及其制备方法 |
CN112759762A (zh) * | 2021-02-05 | 2021-05-07 | 中山大学 | 一种用于肿瘤t1-t2磁共振成像的介孔聚多巴胺纳米粒 |
WO2021262645A1 (en) * | 2020-06-22 | 2021-12-30 | Ohio State Innovation Foundation | Redox-responsive nanoparticle compositions for ocular delivery of therapeutics |
-
2022
- 2022-01-25 CN CN202210090303.1A patent/CN114522181A/zh active Pending
Patent Citations (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN108434462A (zh) * | 2018-03-13 | 2018-08-24 | 中山大学 | 一种介孔聚多巴胺负载羰基锰的多功能纳米诊疗剂及其制备方法与应用 |
CN109276721A (zh) * | 2018-09-19 | 2019-01-29 | 中山大学 | 一种靶向介孔聚多巴胺多功能纳米诊疗剂及其制备方法与应用 |
CN110804180A (zh) * | 2019-10-28 | 2020-02-18 | 长春理工大学 | 聚多巴胺纳米片的制备方法 |
CN111110652A (zh) * | 2020-01-06 | 2020-05-08 | 重庆医科大学 | 一种载药透明质酸聚多巴胺包覆介孔聚多巴胺纳米粒及其制备方法 |
WO2021262645A1 (en) * | 2020-06-22 | 2021-12-30 | Ohio State Innovation Foundation | Redox-responsive nanoparticle compositions for ocular delivery of therapeutics |
CN112603910A (zh) * | 2020-12-31 | 2021-04-06 | 淮阴工学院 | 介孔聚多巴胺载花青素纳米粒及其制备方法 |
CN112759762A (zh) * | 2021-02-05 | 2021-05-07 | 中山大学 | 一种用于肿瘤t1-t2磁共振成像的介孔聚多巴胺纳米粒 |
Non-Patent Citations (1)
Title |
---|
杨勋成: "金属-多酚纳米疫苗的肿瘤免疫治疗及精氨酸掺杂聚多巴胺纳米粒子的抗炎效应研究" * |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
Tang et al. | Dual GSH-exhausting sorafenib loaded manganese-silica nanodrugs for inducing the ferroptosis of hepatocellular carcinoma cells | |
Wang et al. | Oxygen-supplementing mesoporous polydopamine nanosponges with WS2 QDs-embedded for CT/MSOT/MR imaging and thermoradiotherapy of hypoxic cancer | |
Dehvari et al. | Heteroatom doped carbon dots with nanoenzyme like properties as theranostic platforms for free radical scavenging, imaging, and chemotherapy | |
Gholibegloo et al. | Folic acid decorated magnetic nanosponge: An efficient nanosystem for targeted curcumin delivery and magnetic resonance imaging | |
Yang et al. | Hollow structured upconversion luminescent NaYF4: Yb3+, Er3+ nanospheres for cell imaging and targeted anti-cancer drug delivery | |
Tan et al. | Renal-clearable quaternary chalcogenide nanocrystal for photoacoustic/magnetic resonance imaging guided tumor photothermal therapy | |
Liu et al. | Co-delivery of erlotinib and doxorubicin by MoS2 nanosheets for synergetic photothermal chemotherapy of cancer | |
Flak et al. | Hybrid ZnPc@ TiO2 nanostructures for targeted photodynamic therapy, bioimaging and doxorubicin delivery | |
Burke et al. | In-situ synthesis of magnetic iron-oxide nanoparticle-nanofibre composites using electrospinning | |
Gao et al. | Facile one-pot synthesis of Fe 3 O 4@ chitosan nanospheres for MRI and fluorescence imaging guided chemo-photothermal combinational cancer therapy | |
Halevas et al. | Modified magnetic core-shell mesoporous silica nano-formulations with encapsulated quercetin exhibit anti-amyloid and antioxidant activity | |
Pinna et al. | Ceria nanoparticles for the treatment of Parkinson-like diseases induced by chronic manganese intoxication | |
Zhou et al. | Implications for blood-brain-barrier permeability, in vitro oxidative stress and neurotoxicity potential induced by mesoporous silica nanoparticles: Effects of surface modification | |
Miao et al. | Stable and non-toxic ultrasmall gadolinium oxide nanoparticle colloids (coating material= polyacrylic acid) as high-performance T 1 magnetic resonance imaging contrast agents | |
Rehman et al. | In situ self-assembled Ag–Fe 3 O 4 nanoclusters in exosomes for cancer diagnosis | |
Xuan et al. | Bismuth particles imbedded degradable nanohydrogel prepared by one-step method for tumor dual-mode imaging and chemo-photothermal combined therapy | |
Cheng et al. | Preparation and biological characterization of hollow magnetic Fe 3 O 4@ C nanoparticles as drug carriers with high drug loading capability, pH-control drug release and MRI properties | |
Deol et al. | Stability, cytotoxicity and cell uptake of water-soluble dendron–conjugated gold nanoparticles with 3, 12 and 17 nm cores | |
Zhao et al. | High and low molecular weight hyaluronic acid-coated gold nanobipyramids for photothermal therapy | |
Ouyang et al. | Covalent RGD–graphene–phthalocyanine nanocomposite for fluorescence imaging-guided dual active/passive tumor-targeted combinatorial phototherapy | |
Khatibi et al. | Targeted and biocompatible NMOF as efficient nanocomposite for delivery of methotrexate to colon cancer cells | |
Aboushoushah et al. | Toxicity and biodistribution assessment of curcumin-coated iron oxide nanoparticles: Multidose administration | |
Khoee et al. | DOX delivery based on chitosan-capped graphene oxide-mesoporous silica nanohybride as pH-responsive nanocarriers | |
Li et al. | Gadolinium-coated mesoporous silica nanoparticle for magnetic resonance imaging | |
Wang et al. | Implantable composite fibres with Self-supplied H2O2 for localized chemodynamic therapy |
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 |