CN108310388A - The preparation method and its usage of the fluorescence mesoporous silica nano particle of disulfide bond functionalization - Google Patents
The preparation method and its usage of the fluorescence mesoporous silica nano particle of disulfide bond functionalization Download PDFInfo
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- CN108310388A CN108310388A CN201711450730.1A CN201711450730A CN108310388A CN 108310388 A CN108310388 A CN 108310388A CN 201711450730 A CN201711450730 A CN 201711450730A CN 108310388 A CN108310388 A CN 108310388A
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- Prior art keywords
- mesoporous silica
- fluorescence
- silica nano
- nano particle
- disulfide bond
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- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 title claims abstract description 163
- 239000000377 silicon dioxide Substances 0.000 title claims abstract description 79
- 239000002105 nanoparticle Substances 0.000 title claims abstract description 56
- 238000007306 functionalization reaction Methods 0.000 title claims abstract description 31
- 238000002360 preparation method Methods 0.000 title claims abstract description 21
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 99
- 235000019441 ethanol Nutrition 0.000 claims description 53
- 239000000243 solution Substances 0.000 claims description 34
- 239000006185 dispersion Substances 0.000 claims description 30
- 239000007788 liquid Substances 0.000 claims description 20
- 235000012239 silicon dioxide Nutrition 0.000 claims description 20
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 20
- 238000006243 chemical reaction Methods 0.000 claims description 18
- 239000006087 Silane Coupling Agent Substances 0.000 claims description 12
- ZOIORXHNWRGPMV-UHFFFAOYSA-N acetic acid;zinc Chemical compound [Zn].CC(O)=O.CC(O)=O ZOIORXHNWRGPMV-UHFFFAOYSA-N 0.000 claims description 10
- MCJGNVYPOGVAJF-UHFFFAOYSA-N quinolin-8-ol Chemical compound C1=CN=C2C(O)=CC=CC2=C1 MCJGNVYPOGVAJF-UHFFFAOYSA-N 0.000 claims description 10
- 239000004246 zinc acetate Substances 0.000 claims description 10
- 238000005119 centrifugation Methods 0.000 claims description 9
- 229960003540 oxyquinoline Drugs 0.000 claims description 9
- 238000003756 stirring Methods 0.000 claims description 9
- 239000005725 8-Hydroxyquinoline Substances 0.000 claims description 8
- DCPMPXBYPZGNDC-UHFFFAOYSA-N hydron;methanediimine;chloride Chemical compound Cl.N=C=N DCPMPXBYPZGNDC-UHFFFAOYSA-N 0.000 claims description 7
- 238000005406 washing Methods 0.000 claims description 7
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 6
- 150000008065 acid anhydrides Chemical class 0.000 claims description 6
- 239000007822 coupling agent Substances 0.000 claims description 6
- YUFRRMZSSPQMOS-UHFFFAOYSA-N 2-(2-aminoethyldisulfanyl)ethanamine;hydron;dichloride Chemical compound Cl.Cl.NCCSSCCN YUFRRMZSSPQMOS-UHFFFAOYSA-N 0.000 claims description 5
- BLRPTPMANUNPDV-UHFFFAOYSA-N Silane Chemical compound [SiH4] BLRPTPMANUNPDV-UHFFFAOYSA-N 0.000 claims description 5
- 239000007864 aqueous solution Substances 0.000 claims description 5
- WOWHHFRSBJGXCM-UHFFFAOYSA-M cetyltrimethylammonium chloride Chemical group [Cl-].CCCCCCCCCCCCCCCC[N+](C)(C)C WOWHHFRSBJGXCM-UHFFFAOYSA-M 0.000 claims description 5
- 230000000694 effects Effects 0.000 claims description 5
- 229910000077 silane Inorganic materials 0.000 claims description 5
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 4
- NQTADLQHYWFPDB-UHFFFAOYSA-N N-Hydroxysuccinimide Chemical compound ON1C(=O)CCC1=O NQTADLQHYWFPDB-UHFFFAOYSA-N 0.000 claims description 4
- GSEJCLTVZPLZKY-UHFFFAOYSA-N Triethanolamine Chemical compound OCCN(CCO)CCO GSEJCLTVZPLZKY-UHFFFAOYSA-N 0.000 claims description 4
- FPYJFEHAWHCUMM-UHFFFAOYSA-N maleic anhydride Chemical compound O=C1OC(=O)C=C1 FPYJFEHAWHCUMM-UHFFFAOYSA-N 0.000 claims description 4
- 239000000203 mixture Substances 0.000 claims description 4
- 239000002245 particle Substances 0.000 claims description 4
- 239000002243 precursor Substances 0.000 claims description 4
- 238000004321 preservation Methods 0.000 claims description 4
- 239000004094 surface-active agent Substances 0.000 claims description 4
- WYTZZXDRDKSJID-UHFFFAOYSA-N (3-aminopropyl)triethoxysilane Chemical group CCO[Si](OCC)(OCC)CCCN WYTZZXDRDKSJID-UHFFFAOYSA-N 0.000 claims description 3
- DCQBZYNUSLHVJC-UHFFFAOYSA-N 3-triethoxysilylpropane-1-thiol Chemical compound CCO[Si](OCC)(OCC)CCCS DCQBZYNUSLHVJC-UHFFFAOYSA-N 0.000 claims description 3
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 claims description 3
- 239000000908 ammonium hydroxide Substances 0.000 claims description 3
- 239000003795 chemical substances by application Substances 0.000 claims description 3
- 239000006071 cream Substances 0.000 claims description 3
- 239000011259 mixed solution Substances 0.000 claims description 3
- 239000007787 solid Substances 0.000 claims description 3
- 239000000126 substance Substances 0.000 claims description 3
- TXDNPSYEJHXKMK-UHFFFAOYSA-N sulfanylsilane Chemical compound S[SiH3] TXDNPSYEJHXKMK-UHFFFAOYSA-N 0.000 claims description 3
- 239000006228 supernatant Substances 0.000 claims description 3
- -1 γ-mercapto propyl Chemical group 0.000 claims description 3
- FALRKNHUBBKYCC-UHFFFAOYSA-N 2-(chloromethyl)pyridine-3-carbonitrile Chemical compound ClCC1=NC=CC=C1C#N FALRKNHUBBKYCC-UHFFFAOYSA-N 0.000 claims description 2
- UUEWCQRISZBELL-UHFFFAOYSA-N 3-trimethoxysilylpropane-1-thiol Chemical compound CO[Si](OC)(OC)CCCS UUEWCQRISZBELL-UHFFFAOYSA-N 0.000 claims description 2
- BPQQTUXANYXVAA-UHFFFAOYSA-N Orthosilicate Chemical compound [O-][Si]([O-])([O-])[O-] BPQQTUXANYXVAA-UHFFFAOYSA-N 0.000 claims description 2
- BOTDANWDWHJENH-UHFFFAOYSA-N Tetraethyl orthosilicate Chemical compound CCO[Si](OCC)(OCC)OCC BOTDANWDWHJENH-UHFFFAOYSA-N 0.000 claims description 2
- DDXLVDQZPFLQMZ-UHFFFAOYSA-M dodecyl(trimethyl)azanium;chloride Chemical compound [Cl-].CCCCCCCCCCCC[N+](C)(C)C DDXLVDQZPFLQMZ-UHFFFAOYSA-M 0.000 claims description 2
- 150000002466 imines Chemical class 0.000 claims description 2
- WENLKAKVZDPNQX-UHFFFAOYSA-N methanetetrol silicic acid Chemical compound C(O)(O)(O)O.[Si](O)(O)(O)O WENLKAKVZDPNQX-UHFFFAOYSA-N 0.000 claims description 2
- XKBGEWXEAPTVCK-UHFFFAOYSA-M methyltrioctylammonium chloride Chemical compound [Cl-].CCCCCCCC[N+](C)(CCCCCCCC)CCCCCCCC XKBGEWXEAPTVCK-UHFFFAOYSA-M 0.000 claims description 2
- 229910052757 nitrogen Inorganic materials 0.000 claims description 2
- 238000010992 reflux Methods 0.000 claims description 2
- 229940014800 succinic anhydride Drugs 0.000 claims description 2
- HNJXPTMEWIVQQM-UHFFFAOYSA-M triethyl(hexadecyl)azanium;bromide Chemical compound [Br-].CCCCCCCCCCCCCCCC[N+](CC)(CC)CC HNJXPTMEWIVQQM-UHFFFAOYSA-M 0.000 claims description 2
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 claims 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 claims 1
- 241000790917 Dioxys <bee> Species 0.000 claims 1
- 229910003978 SiClx Inorganic materials 0.000 claims 1
- 229910004298 SiO 2 Inorganic materials 0.000 claims 1
- UCKMPCXJQFINFW-UHFFFAOYSA-N Sulphide Chemical compound [S-2] UCKMPCXJQFINFW-UHFFFAOYSA-N 0.000 claims 1
- 235000019270 ammonium chloride Nutrition 0.000 claims 1
- 230000031709 bromination Effects 0.000 claims 1
- 238000005893 bromination reaction Methods 0.000 claims 1
- 239000003937 drug carrier Substances 0.000 claims 1
- 238000000034 method Methods 0.000 claims 1
- 238000002156 mixing Methods 0.000 claims 1
- 125000000913 palmityl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims 1
- UQMOLLPKNHFRAC-UHFFFAOYSA-N tetrabutyl silicate Chemical compound CCCCO[Si](OCCCC)(OCCCC)OCCCC UQMOLLPKNHFRAC-UHFFFAOYSA-N 0.000 claims 1
- GLFDLEXFOHUASB-UHFFFAOYSA-N trimethyl(tetradecyl)azanium Chemical compound CCCCCCCCCCCCCC[N+](C)(C)C GLFDLEXFOHUASB-UHFFFAOYSA-N 0.000 claims 1
- 239000003814 drug Substances 0.000 abstract description 12
- 229940079593 drug Drugs 0.000 abstract description 8
- 230000004048 modification Effects 0.000 abstract description 7
- 238000012986 modification Methods 0.000 abstract description 7
- 239000000463 material Substances 0.000 abstract description 5
- ZLZPEGUSYSQLGL-UHFFFAOYSA-N quinoline zinc Chemical compound [Zn].N1=CC=CC2=CC=CC=C21.N1=CC=CC2=CC=CC=C21 ZLZPEGUSYSQLGL-UHFFFAOYSA-N 0.000 abstract description 4
- 238000013270 controlled release Methods 0.000 abstract description 3
- 238000005516 engineering process Methods 0.000 abstract description 3
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 abstract description 3
- 206010061623 Adverse drug reaction Diseases 0.000 abstract description 2
- 208000030453 Drug-Related Side Effects and Adverse reaction Diseases 0.000 abstract description 2
- 208000003837 Second Primary Neoplasms Diseases 0.000 abstract description 2
- 239000002246 antineoplastic agent Substances 0.000 abstract description 2
- 229940041181 antineoplastic drug Drugs 0.000 abstract description 2
- 239000002539 nanocarrier Substances 0.000 abstract description 2
- 235000013339 cereals Nutrition 0.000 description 29
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 14
- 238000002189 fluorescence spectrum Methods 0.000 description 6
- 238000012377 drug delivery Methods 0.000 description 5
- 230000008685 targeting Effects 0.000 description 4
- 125000003368 amide group Chemical group 0.000 description 3
- 230000005284 excitation Effects 0.000 description 3
- 229910052814 silicon oxide Inorganic materials 0.000 description 3
- 231100000419 toxicity Toxicity 0.000 description 3
- 230000001988 toxicity Effects 0.000 description 3
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 2
- 206010028980 Neoplasm Diseases 0.000 description 2
- 241000209094 Oryza Species 0.000 description 2
- 235000007164 Oryza sativa Nutrition 0.000 description 2
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 2
- 239000005864 Sulphur Substances 0.000 description 2
- 230000005540 biological transmission Effects 0.000 description 2
- 239000007853 buffer solution Substances 0.000 description 2
- 238000005352 clarification Methods 0.000 description 2
- 230000007423 decrease Effects 0.000 description 2
- 238000002866 fluorescence resonance energy transfer Methods 0.000 description 2
- OVBPIULPVIDEAO-LBPRGKRZSA-N folic acid Chemical compound C=1N=C2NC(N)=NC(=O)C2=NC=1CNC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 OVBPIULPVIDEAO-LBPRGKRZSA-N 0.000 description 2
- 125000000524 functional group Chemical group 0.000 description 2
- 239000002953 phosphate buffered saline Substances 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- PYWVYCXTNDRMGF-UHFFFAOYSA-N rhodamine B Chemical compound [Cl-].C=12C=CC(=[N+](CC)CC)C=C2OC2=CC(N(CC)CC)=CC=C2C=1C1=CC=CC=C1C(O)=O PYWVYCXTNDRMGF-UHFFFAOYSA-N 0.000 description 2
- 235000009566 rice Nutrition 0.000 description 2
- 239000000523 sample Substances 0.000 description 2
- 229910052710 silicon Inorganic materials 0.000 description 2
- 239000010703 silicon Substances 0.000 description 2
- 238000001228 spectrum Methods 0.000 description 2
- KIUKXJAPPMFGSW-DNGZLQJQSA-N (2S,3S,4S,5R,6R)-6-[(2S,3R,4R,5S,6R)-3-Acetamido-2-[(2S,3S,4R,5R,6R)-6-[(2R,3R,4R,5S,6R)-3-acetamido-2,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-2-carboxy-4,5-dihydroxyoxan-3-yl]oxy-5-hydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-3,4,5-trihydroxyoxane-2-carboxylic acid Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@H](O3)C(O)=O)O)[C@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](C(O)=O)O1 KIUKXJAPPMFGSW-DNGZLQJQSA-N 0.000 description 1
- OVBPIULPVIDEAO-UHFFFAOYSA-N N-Pteroyl-L-glutaminsaeure Natural products C=1N=C2NC(N)=NC(=O)C2=NC=1CNC1=CC=C(C(=O)NC(CCC(O)=O)C(O)=O)C=C1 OVBPIULPVIDEAO-UHFFFAOYSA-N 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- XUIMIQQOPSSXEZ-UHFFFAOYSA-N Silicon Chemical compound [Si] XUIMIQQOPSSXEZ-UHFFFAOYSA-N 0.000 description 1
- MCEBKLYUUDGVMD-UHFFFAOYSA-N [SiH3]S(=O)=O Chemical compound [SiH3]S(=O)=O MCEBKLYUUDGVMD-UHFFFAOYSA-N 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 238000000862 absorption spectrum Methods 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 230000001476 alcoholic effect Effects 0.000 description 1
- 125000005211 alkyl trimethyl ammonium group Chemical group 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 239000012876 carrier material Substances 0.000 description 1
- 238000006555 catalytic reaction Methods 0.000 description 1
- 210000004027 cell Anatomy 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 239000000084 colloidal system Substances 0.000 description 1
- 150000004696 coordination complex Chemical class 0.000 description 1
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 1
- 230000000857 drug effect Effects 0.000 description 1
- 238000002296 dynamic light scattering Methods 0.000 description 1
- 230000005611 electricity Effects 0.000 description 1
- 210000001163 endosome Anatomy 0.000 description 1
- 230000002255 enzymatic effect Effects 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 229940031098 ethanolamine Drugs 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 229960000304 folic acid Drugs 0.000 description 1
- 235000019152 folic acid Nutrition 0.000 description 1
- 239000011724 folic acid Substances 0.000 description 1
- 229920002674 hyaluronan Polymers 0.000 description 1
- 229960003160 hyaluronic acid Drugs 0.000 description 1
- 230000036571 hydration Effects 0.000 description 1
- 238000006703 hydration reaction Methods 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 229910052738 indium Inorganic materials 0.000 description 1
- 230000003902 lesion Effects 0.000 description 1
- 210000003712 lysosome Anatomy 0.000 description 1
- 230000001868 lysosomic effect Effects 0.000 description 1
- 239000013335 mesoporous material Substances 0.000 description 1
- ARYZCSRUUPFYMY-UHFFFAOYSA-N methoxysilane Chemical compound CO[SiH3] ARYZCSRUUPFYMY-UHFFFAOYSA-N 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- 238000010606 normalization Methods 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- VDGJOQCBCPGFFD-UHFFFAOYSA-N oxygen(2-) silicon(4+) titanium(4+) Chemical compound [Si+4].[O-2].[O-2].[Ti+4] VDGJOQCBCPGFFD-UHFFFAOYSA-N 0.000 description 1
- 230000004962 physiological condition Effects 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 229920000642 polymer Polymers 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
- 239000000376 reactant Substances 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 229940043267 rhodamine b Drugs 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 230000001568 sexual effect Effects 0.000 description 1
- RMAQACBXLXPBSY-UHFFFAOYSA-N silicic acid Chemical compound O[Si](O)(O)O RMAQACBXLXPBSY-UHFFFAOYSA-N 0.000 description 1
- 230000006641 stabilisation Effects 0.000 description 1
- 238000011105 stabilization Methods 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 125000003396 thiol group Chemical class [H]S* 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- CEYYIKYYFSTQRU-UHFFFAOYSA-M trimethyl(tetradecyl)azanium;chloride Chemical compound [Cl-].CCCCCCCCCCCCCC[N+](C)(C)C CEYYIKYYFSTQRU-UHFFFAOYSA-M 0.000 description 1
- 229910021642 ultra pure water Inorganic materials 0.000 description 1
- 239000012498 ultrapure water Substances 0.000 description 1
- 239000011701 zinc Substances 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
- A61K47/02—Inorganic compounds
-
- 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
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
-
- 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
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K49/00—Preparations for testing in vivo
- A61K49/001—Preparation for luminescence or biological staining
- A61K49/0013—Luminescence
- A61K49/0017—Fluorescence in vivo
- A61K49/0019—Fluorescence in vivo characterised by the fluorescent group, e.g. oligomeric, polymeric or dendritic molecules
- A61K49/0021—Fluorescence in vivo characterised by the fluorescent group, e.g. oligomeric, polymeric or dendritic molecules the fluorescent group being a small organic molecule
- A61K49/0041—Xanthene dyes, used in vivo, e.g. administered to a mice, e.g. rhodamines, rose Bengal
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K49/00—Preparations for testing in vivo
- A61K49/001—Preparation for luminescence or biological staining
- A61K49/0013—Luminescence
- A61K49/0017—Fluorescence in vivo
- A61K49/005—Fluorescence in vivo characterised by the carrier molecule carrying the fluorescent agent
- A61K49/0052—Small organic molecules
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K49/00—Preparations for testing in vivo
- A61K49/001—Preparation for luminescence or biological staining
- A61K49/0063—Preparation for luminescence or biological staining characterised by a special physical or galenical form, e.g. emulsions, microspheres
- A61K49/0069—Preparation for luminescence or biological staining characterised by a special physical or galenical form, e.g. emulsions, microspheres the agent being in a particular physical galenical form
- A61K49/0089—Particulate, powder, adsorbate, bead, sphere
- A61K49/0091—Microparticle, microcapsule, microbubble, microsphere, microbead, i.e. having a size or diameter higher or equal to 1 micrometer
- A61K49/0093—Nanoparticle, nanocapsule, nanobubble, nanosphere, nanobead, i.e. having a size or diameter smaller than 1 micrometer, e.g. polymeric nanoparticle
Abstract
The invention discloses a kind of preparation method and its usages of the fluorescence mesoporous silica nano particle of disulfide bond functionalization, belong to pharmaceutical technology field.The preparation method includes preparing mercapto-modified mesoporous silica nano-particle first, then using quinoline zinc and amino as modification group, it is protected from light the lower fluorescence mesoporous silica nano grain for reacting at room temperature and disulfide bond functionalization being prepared, its grain size is 80~150nm, and photoluminescent property is stablized, and can effectively improve drugloading rate Drug controlled release as the nano carrier material of conveying antitumor drug, drug side-effect is reduced, to effective treatment-related cancer.
Description
Technical field
The present invention relates to mesoporous silicon dioxide nano particle, belong to pharmaceutical technology field, more particularly to a kind of disulfide bond
The preparation method and its usage of the fluorescence mesoporous silica nano particle of functionalization.
Background technology
Drug may be implemented in the Targeting delivery of lesions position in controlled release drug delivery system, improves drug effect, reduces drug
Toxic side effect.Ideal controlled release drug delivery system requires the drug of load in the leading zero release for reaching targeted site position, arrives
It is just released after up to target targeting.
Mesoporous silicon dioxide nano particle (MSNs) is in drug delivery system, catalysis and absorption, Separation of Proteins etc.
It has a wide range of applications, incomparable advantage is especially shown in drug delivery system：With big specific surface area (＞
900m2/ g) and specific pore volume (0.9 cm of ＞3/ g), adjustable aperture (2~10nm), controllable form and modifiable table
Face can load various drugs in mesoporous channel or in mesopore surfaces, and can carry out controllable load medicine to drug and be released with drug
It puts, may finally realize the targeting to tissue.At present it has been reported that a series of stimuli responsive sexual systems based on MSNs, i.e. medicine
Object release can be by including temperature, electricity, magnetic field, the physical signals such as light and pH, redox, these environment of the chemical signals such as enzymatic activity
Stimulation triggering, to realize that MSNs provides bright prospects in the application of medicine controlled releasing delivery system.
Wherein, the Metaporous silicon dioxide material of hole wall fluorescent functional due to it have stable fluorescence property can be used as it is glimmering
Light probe just increasingly causes extensive concern, however, some fluorescence mesoporous materials due to itself toxicity or be exposed to material table
Face leads to the unusual death of normal cell, can all influence therapeutic effect；Therefore, it designs and prepares steady with the smaller height of toxicity
Mesoporous silicon dioxide nano particle of qualitative novel fluorescence functionalization, pass is applied to realizing it in drug delivery field
It is important.
Invention content
In order to solve the above technical problems, the invention discloses have that toxicity is smaller and the disulfide bond functionalization of high stability
The preparation method and its usage of fluorescence mesoporous silica nano particle.
To achieve the above object, the invention discloses a kind of fluorescence mesoporous silica nano particles of disulfide bond functionalization
Preparation method, it includes the following steps：
1) alcohol dispersion liquid of mercapto-modified mesoporous silicon dioxide nano particle is prepared；
2) alcohol dispersion liquid of fluorescence mesoporous silica nano grain is prepared：Step 1) is taken to prepare mercapto-modified mesoporous
The alcohol dispersion liquid of silica dioxide nano particle, Centrifugal dispersion react in zinc acetate solution, then with 8-hydroxyquinoline in the case where being protected from light,
Fluorescence mesoporous silica nano grain is prepared, is scattered in the ethyl alcohol point for obtaining fluorescence mesoporous silica nano grain in ethyl alcohol
Dispersion liquid；
3) aqueous dispersions of the fluorescence mesoporous silica nano grain of carboxyl-functional are prepared：It is even that silane is added into acid anhydrides
Join agent, is stirred to react to obtain the silane coupling agent of carboxyl-functional, the fluorescence mesoporous silicon oxide that step 2) obtains is taken to receive
The ethanol solution of the grain of rice sequentially adds the silane coupling agent of aqueous slkali, carboxyl-functional, is protected from light to obtain carboxyl-functional
Fluorescence mesoporous silica nano grain, is dispersed in water, and obtains the water of the fluorescence mesoporous silica nano grain of carboxyl-functional
Dispersion liquid；
4) aqueous dispersions of the fluorescence mesoporous silica nano grain of disulfide bond functionalization are prepared：Step 3) is taken to be prepared
Carboxyl-functional fluorescence mesoporous silica nano grain aqueous dispersions, sequentially add 1- ethyls-(3- dimethylaminos third
Base) carbodiimide hydrochloride and n-hydroxysuccinimide, then the aqueous solution of 2-aminoethyl disulfide dihydrochloride is added dropwise and is protected from light and is prepared into
To the fluorescence mesoporous silica nano grain of disulfide bond functionalization, it is dispersed in water preservation.
Further, in the step 2), the second of the mercapto-modified mesoporous silicon dioxide nano particle of step 1) preparation is taken
Alcohol dispersion liquid, Centrifugal dispersion are stirred to react 10~14h in zinc acetate solution, then centrifuge, are dispersed in water after ethyl alcohol washing
Be prepared into and wait for reaction solution, take the ethanol solution of 8-hydroxyquinoline under stirring, be added drop-wise to it is described wait in reaction solution, at room temperature
It is protected from light 40~56h, it is colourless to be washed after reaction to supernatant through centrifugation, ethyl alcohol, obtains fluorescence mesoporous silicon oxide
Nanoparticle is dispersed to the alcohol dispersion liquid that fluorescence mesoporous silica nano grain is obtained in ethyl alcohol.
Still further, in the step 2), 0.4 is added in the mercapto-modified mesoporous silicon dioxide nano particle per 0.1g
The 8-hydroxyquinoline of~0.5mmoL, the zinc acetate of 0.047~0.095mmoL, zinc acetate solution a concentration of 0.05~
0.08mol/L。
Further, in the step 3), under condition of ice bath, silane coupling agent is added into acid anhydrides, is stirred to react
To white cream solid is become, the silane coupling agent of carboxyl-functional is obtained, stored refrigerated, the fluorescence for taking step 2) to obtain
The ethanol solution of mesoporous silicon dioxide nano particle sequentially adds the silane coupling agent of aqueous slkali, carboxyl-functional, is protected from light at room temperature
10~14h is reacted, centrifugation after the reaction was complete, ethyl alcohol washing obtains the fluorescence mesoporous silica nano grain of carboxyl-functional, point
It is dissipated in water and preserves.
Further, in the step 3), the aqueous slkali is at least one of ammonium hydroxide, triethanolamine, the silicon
Alkane coupling agent is 3- aminopropyl triethoxysilanes, and the acid anhydrides is at least one of maleic anhydride or succinic anhydride.
Still more preferably, in the step 4), 1- ethyls-(3- dimethylaminopropyls) carbodiimide hydrochloride
The amount ratio of the substance of salt and n-hydroxysuccinimide is 1~10:1.
Still more preferably, it in the step 4), is added in the fluorescence mesoporous silica nano grain per 0.1g
The 1- ethyls-(3- dimethylaminopropyls) of the silane coupling agent of the carboxyl-functional of 0.326mmol, 0.625~6.25 mmol
The 2-aminoethyl disulfide dihydrochloride of carbodiimide hydrochloride, the n-hydroxysuccinimide of 0.625mmol and 0.324~3.24mmol.
Further, it in the step 1), is added in triethanolamine, stirs after taking ethyl alcohol, water to be mixed with surfactant
It mixes to dissolving, then under nitrogen protection effect, controlled at 40~90 DEG C, silica precursor and hydrosulphonyl silane is added dropwise
The mixed solution of coupling agent stirs 2h, then cools to room temperature, is washed 2~3 times using ethyl alcohol after centrifugation for the first time, then
It is 9 in volume ratio:1 ethyl alcohol controlled at 60 DEG C, flows back 2~3 times, returns with the mixed solution system of 37wt% hydrochloric acid
It is centrifuged using alternately washing 5~6 times of second alcohol and water, second after stream, mercapto is prepared in redisperse to ethyl alcohol
The alcohol dispersion liquid of the mesoporous silicon dioxide nano particle of base modification.
Still more preferably, in the step 1), the surfactant is hexadecyltrimethylammonium chloride, 16
Alkyl trimethyl ammonium bromide, cetyltriethylammonium bromide, tri-n-octyl methyl ammonium chloride, dodecyl trimethyl ammonium chloride or
One or more kinds of mixtures in tetradecyl trimethyl ammonium chloride；
The silica precursor is tetraethyl orthosilicate, positive quanmethyl silicate, positive silicic acid orthocarbonate, four fourth of positive silicic acid
One or more kinds of mixtures in ester；
The mercaptosilane coupling agents are mercaptopropyl trimethoxysilane, mercaptopropyltriethoxysilane, γ-mercapto propyl three
At least one of methoxy silane.
In order to preferably realize technical scheme of the present invention, the invention also discloses be prepared using above-mentioned preparation method
Disulfide bond functionalization fluorescence mesoporous silica nano particle, the grain size of the mesoporous silica nano-particle is 80~
150nm。
In addition, the invention also discloses the fluorescence mesoporous silica nano grains of the disulfide bond functionalization of above-mentioned preparation in medicine
Application in object carrier.
As the preferred of technical solution of the present invention：
Per 0.1g mercapto-modified mesoporous silicon dioxide nano particle in be added 0.475mmoL 8-hydroxyquinoline,
The zinc acetate of 0.067mmoL；
The silane coupled of the carboxyl-functional of 0.326mmol is added in fluorescence mesoporous silica nano grain per 0.1g
Agent, 1- ethyls-(3- dimethylaminopropyls) carbodiimide hydrochloride of 0.625mmol, 0.625mmol N- hydroxysuccinimidyl acyls
The 2-aminoethyl disulfide dihydrochloride of imines and 3.24mmol.
Advantageous effect：
1, the grain size of the fluorescence mesoporous silica nano particle of disulfide bond functionalization prepared by the present invention be 80~
150nm, and particle size dispersion is uniform；
2, the fluorescence mesoporous silica nano particle of disulfide bond functionalization prepared by the present invention in hole inner wall due to modifying
There is quinoline zinc, makes nano-particle characteristic with fluoresced green under 380nm excitations, and in the buffer solution of (5~9) pH=
In, photoluminescent property is stablized；
3, the fluorescence mesoporous silica nano particle surface of disulfide bond functionalization prepared by the present invention is modified with containing two sulphur
The amido functional group of key makes the nano-particle that there is the characteristic of reduction response, nano-particle can utilize the amido functional group on surface
Can further modified high molecular polymer improve nanoparticle biocompatibility molecule polyethylene glycol, point with targeting
Sub such as hyaluronic acid or folic acid and with the molecule such as rhodamine with quinoline zinc generation fluorescence resonance energy transfer；It can be used as
The nano carrier material of antitumor drug is conveyed, which has the function of monitoring in real time, can effectively improve drugloading rate control
Drug release processed reduces drug side-effect, to effective treatment-related cancer.
Description of the drawings
Fig. 1 is the transmission electron microscope picture of CMS-SH of the embodiment of the present invention；
Fig. 2 is the transmission electron microscope picture of Znq-CMS of the embodiment of the present invention；
Fig. 3 is fluorescence spectra of Znq-CMS of the embodiment of the present invention samples under 380nm wavelength；
Fig. 4 is fluorescence spectra of the Znq-CMS samples of Fig. 3 under different time；
Fig. 5 is fluorescence spectra of the Znq-CMS samples of Fig. 3 under different pH buffer solutions；
Fig. 6 is the fluorescence photo of Fig. 5；
Fig. 7 is Znq-CMS, Znq-CMS-COOH and Znq-CMS-SS-NH of the embodiment of the present invention2Normalization fluorescence light
Spectrum；
Fig. 8 is the fluorescence photo of Fig. 7.
Specific implementation mode
In order to preferably explain the present invention, below in conjunction with the specific embodiment main contents that the present invention is furture elucidated, but
Present disclosure is not limited solely to following embodiment.
The invention discloses a kind of preparation methods of the fluorescence mesoporous silica nano particle of disulfide bond functionalization, it is wrapped
Include following steps：
1) alcohol dispersion liquid of mercapto-modified mesoporous silicon dioxide nano particle (CMS-SH) is prepared：25wt% (quality hundred
Point ratio) hexadecyltrimethylammonium chloride (CTAC) aqueous solution preparation：3.5gCTAC is taken to be dissolved in 10.5mL water, at room temperature
20 min are vigorously stirred, until clarification；
It takes 64mL water, 10.5mL ethyl alcohol, 10.4mL25wt%CTAC aqueous solutions to be vigorously stirred 10min at room temperature, is added three
Ethanol amine 4.125mL continues to be vigorously stirred 15min, until clarification is used as storing solution；20mL storing solutions are taken to be placed in three-necked flask
In, in N2After temperature stabilization, the positive silicon of 1.454mL is then added dropwise to 60 DEG C in the lower oil bath of protection under stiring in 2~3min
The mixed liquor of sour tetra-ethyl ester (TEOS) and 0.1625mL mercaptopropyltriethoxysilanes (MPTES), continues to be stirred to react 2h, from
The heart is washed 2 times with ethyl alcohol；Above-mentioned solution is redispersed in the ethanol solution containing 5mL hydrochloric acid (37wt%) and 45mL, 60 DEG C
Refluxing extraction 2h, is repeated twice, and ethyl alcohol washs 6 times, is finally scattered in the solution preservation that 5mg/mL is configured in ethanol solution.
2) alcohol dispersion liquid of fluorescence mesoporous silica nano grain (Znq-CMS) is prepared：In the step 2), 20mL is taken
CMS-SH alcohol dispersion liquids prepared by the step 1) of 5mg/mL, are scattered in the zinc acetate of a concentration of 0.05mol/L of 9.5mL after centrifugation
In solution, ultrasonic disperse is uniform, is stirred to react 12h at room temperature, then centrifuge, ethyl alcohol wash 3 times after be dispersed in water be prepared into it is dense
Degree waits for reaction solution for 5mg/mL's, takes and waits for reaction solution 20mL, ultrasonic disperse is uniform, and 25mL is contained 9.7mg (0.067mmol) 8-
The ethanol solution of oxyquinoline (8-Hq) under stirring, be added drop-wise to dropwise it is described wait in reaction solution, be protected from light at room temperature
48h obtains fluorescence mesoporous silicon oxide and receives after reaction through centrifuging, using ethyl alcohol to wash 3~5 times to supernatant to be colourless
The grain of rice (Znq-CMS) is dispersed in ethyl alcohol and obtains a concentration of 5mg/mL solution preservation.
3) aqueous dispersions of the fluorescence mesoporous silica nano grain (Znq-CMS-COOH) of carboxyl-functional are prepared：
2.5g (25.5mmol) maleic anhydride is taken to be placed in the 25mL round-bottomed flasks equipped with rotor, under condition of ice bath, by
5.5mL (23.5mmol) 3- aminopropyl triethoxysilanes (APTES) are added dropwise to, are quickly stirred to react, it is seen that maleic anhydride is molten
Amount of heat is solved and releases, stirring stops reaction after becoming white cream solid to reactant, obtains the silane of carboxyl-functional
Coupling agent (APTES-COOH) places it in the Znq-CMS ethyl alcohol stored refrigerated in refrigerator, 20mL steps 2) is taken to obtain
Solution (5mg/mL), ultrasonic disperse is uniform, and 10uL ammonium hydroxide is then added under stirring, 104mg APTES-COOH is taken to be dissolved in
2 mL ethyl alcohol, are added dropwise in above-mentioned reaction solution, are protected from light 12h at room temperature, and centrifugation after the reaction was complete, ethyl alcohol washs 3 times,
The fluorescence mesoporous silica nano grain (Znq-CMS-COOH) of carboxyl-functional is obtained, is dispersed in 20mL water, obtains carboxyl
The aqueous dispersions of the fluorescence mesoporous silica nano grain of functionalization.
4) fluorescence mesoporous silica nano grain (the Znq-CMS-SS- NH of disulfide bond functionalization are prepared2) it is water-dispersed
Liquid：The Znq-CMS-COOH aqueous dispersions that step 3) is prepared are taken, 120mg 1- ethyl-(3- dimethylaminopropyls) is added
Carbodiimide hydrochloride (EDCHCl) is stirred at room temperature reaction 10min, then adds 80mg n-hydroxysuccinimides
(NHS) reaction activation 1h, then 0.5g 2-aminoethyl disulfide dihydrochlorides is taken to be dissolved in 5mL water, and be added dropwise in above-mentioned reaction solution, room temperature is protected from light
12h is stirred, obtained product is detached with 10000 r/min centrifugations 15min, and washing is resuspended three times in ultra-pure water, obtains containing two sulphur
Fluorescence mesoporous silica nano particle (the Znq-CMS-SS-NH of the amino terminal of key2), it is redispersed in water and is configured to
The solution of 5mg/mL preserves.
The intermediary and product prepared to above-described embodiment 1 carries outDynamic light scattering particle size(DLS) it analyzes, has obtained table
1；
Table 1CMS-SH, Znq-CMS, Znq-CMS-COOH and Znq-CMS-SS-NH2DLS analyze data list
| Sample | Size | PDI | Z- current potentials |
| CMS-SH | 113.2 | 0.088 | -27.8 |
| Znq-CMS | 123.9 | 0.094 | -16.5 |
| Znq-CMS-COOH | 171.5 | 0.073 | -43.4 |
| Znq-CMS-SS-NH2 | 134.1 | 0.108 | +30.6 |
By above-mentioned table 1 it is found that mercapto-functionalized mesoporous silicon dioxide nano particle seed diameter is 113.2nm, PDI is
0.088, it is -27.8mV to have good dispersibility, current potential, negatively charged mainly since meso-porous titanium dioxide silicon face exists greatly
The silanol hydroxyl of amount；When introducing Zn in duct2+After 8-hydroxyquinoline, Znq-CMS current potentials increase, this may be Zn2+With part
The hydroxyl effect on nanoparticle surface as a result, however grain size is 123.9nm changes unobvious compared to CMS-SH, PDI is
0.094 presents good dispersibility, and Znq-CMS is after carboxyl modified, and hydration grain size is 171.5nm, compared to Znq-CMS
Nearly 50nm is increased, reason may be that the parent of nano-particle is increased after carboxyl modified since carboxyl is hydrophilic radical
Aqueous, therefore hydrated sheath becomes larger so as to cause the increase of grain size；Znq-CMS-SS-NH after being modified further across cystamine2Grain
Diameter is 134.1nm, close with Znq-CMS, and the PDI of the nano-particle after modification shows its good dispersion 0.1 or so
Property.It should be noted, however, that the Znq-CMS-COOH and Znq-CMS-SS-NH after modified with functional group2Current potential occur
Apparent variation.
In conjunction with Fig. 1 and Fig. 2 it is found that CMS-SH shows spherical morphology and is evenly distributed, particle size is relatively uniform, puts down
Equal grain size is about 85nm, in addition, apparent vermiform mesopore orbit can be observed, this is colloid mesoporous silicon dioxide nano particle
The feature of son.It is worth noting that, Znq-CMS is also presented spherical morphology and is evenly distributed, and average grain diameter 85nm, mesoporous knot
Structure is still apparent, shows that the doping of metal complex is smaller to meso-hole structure and grain diameter influence.
The alcohol dispersion liquid of Znq-CMS has strong green fluorescence under ultra violet lamp, as shown in figure 3, when excitation
Wavelength is 380nm, and when slit is 10nm, fluorescence emission wavelengths are in 510nm；In conjunction with Fig. 4 it is found that by Znq-CMS samples in second
After being preserved 1 month and 2 months in alcoholic solution, significant change, explanation do not occur for fluorescence emission wavelengths and fluorescence intensity
Photoluminescent property keeps stable to Znq-CMS relatively within a certain period of time.
In order to further investigate influences of the different pH to Znq-CMS photoluminescent properties, Znq-CMS is placed in different pH's
In phosphate buffered saline solution (PBS), and in the UV lamp under irradiation, when excitation wavelength is 365nm, and slit is 10nm, as a result
As shown in figure 5, by Fig. 5 it is found that when in PBSs of the pH more than or equal to 5, the fluorescence intensity of Znq-CMS keeps relative stability,
However when pH is less than 5, fluorescence intensity weakens significantly, or even is almost quenched when pH drops to 3；And document report tumor group
It knits the pH minimums of endosome or lysosome in microenvironment and reaches 5.0 or so, therefore, Znq-CMS is in physiological condition and tumour micro-loop
Fluorescence intensity in border will not be influenced by very big, can be applied to carrier material, specific fluorescence photo as shown in fig. 6, Fig. 6 also again
When secondary proof pH is more than or equal to 5, the fluorescence intensity of Znq-CMS keeps relative stability in green, and the fluorescence when pH drops to 3
Almost it is quenched.
In addition, in order to confirm the modification of each step, such as quinoline zinc and amino to the glimmering of mesoporous silicon dioxide nano particle
Whether light spectrum changes, and the fluorescence spectrum of obtained material after each step modification is determined, as shown in fig. 7, wherein Znq-CMS
After carboxyl and amido modified containing disulfide bond, fluorescence emission peak maximum position has been moved to 495nm by 510nm indigo plants before
Place, but its fluorescence spectrum still have with the absorption spectrum of the receptor rhodamine B of FRET it is overlapping, do not influence fluorescence resonance energy turn
Move the structure of nano-particle FRET-CMS.In addition, the fluorescence spectrum is the collection of illustrative plates of normalized, as modification number increases,
Fluorescence intensity also accordingly decreases, and is consistent with the result of fluorescence photo under Fig. 8 ultra violet lamps, finds out modification from photo
Front and back green fluorescence and the fluorescence intensity of presenting decreases.
Above example is only best citing, rather than a limitation of the embodiments of the present invention.Except above-described embodiment
Outside, the present invention also has other embodiment.All technical solutions formed using equivalent substitution or equivalent transformation, all fall within the present invention
It is required that protection domain.
Claims (10)
1. a kind of preparation method of the fluorescence mesoporous silica nano particle of disulfide bond functionalization, it is characterised in that：It includes
Following steps：
1) mercapto-modified mesoporous silicon dioxide nano particle is prepared, is scattered in ethyl alcohol and preserves；
2) fluorescence mesoporous silica nano particle is prepared：The mercapto-modified mesoporous silicon dioxide nano particle for taking step 1) to prepare
The alcohol dispersion liquid of son, is scattered in zinc acetate solution, then reacted with 8-hydroxyquinoline in the case where being protected from light after centrifugation, is prepared glimmering
Light mesoporous silicon dioxide nano particle, is scattered in ethyl alcohol and preserves；
3) aqueous dispersions of the fluorescence mesoporous silica nano grain of carboxyl-functional are prepared：It is added into acid anhydrides silane coupled
Agent is stirred to react to obtain the silane coupling agent of carboxyl-functional, the fluorescence mesoporous silica nano for taking step 2) to obtain
The alcohol dispersion liquid of grain, sequentially adds the silane coupling agent of aqueous slkali, carboxyl-functional, is protected from light to obtain carboxyl-functional
Fluorescence mesoporous silica nano grain, is dispersed in water, and obtains the water of the fluorescence mesoporous silica nano grain of carboxyl-functional
Dispersion liquid；
4) aqueous dispersions of the fluorescence mesoporous silica nano grain of disulfide bond functionalization are prepared：Take the carboxylic that step 3) is prepared
The aqueous dispersions of the fluorescence mesoporous silica nano grain of base functionalization sequentially add 1- ethyls-(3- dimethylaminopropyls)
Carbodiimide hydrochloride and n-hydroxysuccinimide, then the aqueous solution of 2-aminoethyl disulfide dihydrochloride is added dropwise and is protected from light and is prepared two
The fluorescence mesoporous silica nano of sulfide linkage functionalization is dispersed in water preservation.
2. the preparation method of the fluorescence mesoporous silica nano particle of disulfide bond functionalization according to claim 1, special
Sign is：In the step 2), mercapto-modified mesoporous silicon dioxide nano particle prepared by step 1) is taken to be scattered in zinc acetate molten
In liquid, it is stirred to react 10~14h, then centrifuged, be dispersed to be prepared into water after ethyl alcohol washing and wait for reaction solution, 8-hydroxyquinoline is taken
Ethanol solution under stirring, be added drop-wise to it is described wait in reaction solution, be protected from light 40~56h at room temperature, pass through after reaction
It is colourless that centrifugation, ethyl alcohol, which are washed to supernatant, obtains fluorescence mesoporous silica nano grain, is dispersed in ethyl alcohol and obtains fluorescence Jie
The alcohol dispersion liquid of hole silica dioxide nano particle.
3. the preparation method of the fluorescence mesoporous silica nano particle of disulfide bond functionalization according to claim 2, special
Sign is：It is added 0.4~0.5mmoL's in the step 2), in the mercapto-modified mesoporous silicon dioxide nano particle per 0.1g
The zinc acetate of 8-hydroxyquinoline, 0.047~0.095mmoL, a concentration of 0.05~0.08mol/L of the zinc acetate solution.
4. according to the preparation side of the fluorescence mesoporous silica nano particle of claims 1 or 2 or the 3 disulfide bond functionalization
Method, it is characterised in that：In the step 3), under condition of ice bath, silane coupling agent is added into acid anhydrides, is stirred to react to becoming
White cream solid obtains the silane coupling agent of carboxyl-functional, stored refrigerated, the fluorescence mesoporous two for taking step 2) to obtain
The ethanol solution of silica nanoparticle sequentially adds the silane coupling agent of aqueous slkali, carboxyl-functional, is protected from light 10 at room temperature
~14h, centrifugation after the reaction was complete, ethyl alcohol washing obtain the fluorescence mesoporous silica nano grain of carboxyl-functional, are dispersed to water
In, obtain the aqueous solution of the fluorescence mesoporous silica nano grain of carboxyl-functional.
5. the preparation method of the fluorescence mesoporous silica nano particle of disulfide bond functionalization according to claim 4, special
Sign is：In the step 3), the aqueous slkali is at least one of ammonium hydroxide, triethanolamine, and the silane coupling agent is 3-
Aminopropyl triethoxysilane, the acid anhydrides are at least one of maleic anhydride or succinic anhydride.
6. the preparation method of the fluorescence mesoporous silica nano particle of disulfide bond functionalization according to claim 5, special
Sign is：In the step 4), 1- ethyls-(3- dimethylaminopropyls) carbodiimide hydrochloride and N- hydroxysuccinimidyl acyls
The amount ratio of the substance of imines is 1~10:1.
7. the preparation method of the fluorescence mesoporous silica nano particle of disulfide bond functionalization according to claim 1, special
Sign is：In the step 1), it is added in triethanolamine after taking ethyl alcohol, water to be mixed with surfactant, stirring is extremely dissolved, then
Under nitrogen protection effect, controlled at 40~90 DEG C, the mixing that silica precursor and mercaptosilane coupling agents is added dropwise is molten
Liquid, stir 2h, then cool to room temperature, for the first time centrifuge after using ethyl alcohol wash 2~3 times, then volume ratio be 9:1
Ethyl alcohol controlled at 60 DEG C, flows back 2~3 times with the mixed solution system of 37wt% hydrochloric acid, ethyl alcohol is used after reflux
With water alternately washing 5~6 times, centrifuges for the second time, mercapto-modified mesoporous dioxy is prepared in redisperse to ethyl alcohol
The alcohol dispersion liquid of SiClx nanoparticle.
8. the preparation method of the fluorescence mesoporous silica nano particle of disulfide bond functionalization according to claim 7, special
Sign is：In the step 1), the surfactant is hexadecyltrimethylammonium chloride, cetyl trimethyl bromination
Ammonium, cetyltriethylammonium bromide, tri-n-octyl methyl ammonium chloride, dodecyl trimethyl ammonium chloride or tetradecyltrimethylammonium
One or more kinds of mixtures in ammonium chloride；
The silica precursor is in tetraethyl orthosilicate, positive quanmethyl silicate, positive silicic acid orthocarbonate, positive tetrabutyl silicate
One or more kinds of mixtures；
The mercaptosilane coupling agents are mercaptopropyl trimethoxysilane, mercaptopropyltriethoxysilane, γ-mercapto propyl trimethoxy
At least one of base silane.
9. the fluorescence for the disulfide bond functionalization that the preparation method according to any one of claim 1~8 is prepared is situated between
Hole nano SiO 2 particle, it is characterised in that：The grain size of the mesoporous silica nano-particle is 80~150nm.
10. a kind of fluorescence mesoporous silica nano particle of the disulfide bond functionalization described in claim 9 is in pharmaceutical carrier
Application.
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| CN110217801A (en) * | 2019-05-23 | 2019-09-10 | 首都医科大学 | The mesoporous silicon oxide nanomaterial and the preparation method and application thereof of lipoic acid functionalization |
| CN111701032A (en) * | 2020-06-23 | 2020-09-25 | 重庆大学附属肿瘤医院 | Preparation method of mesoporous silicon oxide complex with drug controlled release and imaging functions |
| CN112843250A (en) * | 2021-01-27 | 2021-05-28 | 中国科学院宁波材料技术与工程研究所 | Nanometer medicinal preparation for treating tumor with iron death and gas synergistic effect, and its preparation method |
| CN115006544A (en) * | 2022-01-25 | 2022-09-06 | 昆明理工大学 | Preparation method and application of functional mesoporous silica eutectic hydrogel system |
| CN115006544B (en) * | 2022-01-25 | 2023-08-18 | 昆明理工大学 | Preparation method and application of functionalized mesoporous silica eutectic hydrogel system |
| CN115005219A (en) * | 2022-05-23 | 2022-09-06 | 广东省科学院生物与医学工程研究所 | Bidirectional-conduction fluorescent nano bactericide and preparation method thereof |
| CN115005219B (en) * | 2022-05-23 | 2024-04-16 | 广东省科学院生物与医学工程研究所 | Bidirectional-conduction fluorescent nano bactericide and preparation method thereof |
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Application publication date: 20180724 |