CN114209852B - 一种声响应型载药棒状介孔硅及其制备方法与应用 - Google Patents
一种声响应型载药棒状介孔硅及其制备方法与应用 Download PDFInfo
- Publication number
- CN114209852B CN114209852B CN202111661894.5A CN202111661894A CN114209852B CN 114209852 B CN114209852 B CN 114209852B CN 202111661894 A CN202111661894 A CN 202111661894A CN 114209852 B CN114209852 B CN 114209852B
- Authority
- CN
- China
- Prior art keywords
- mesoporous silicon
- rod
- stirring
- carrying
- doxorubicin
- 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
- 229910052710 silicon Inorganic materials 0.000 title claims abstract description 80
- 239000010703 silicon Substances 0.000 title claims abstract description 80
- 239000003814 drug Substances 0.000 title claims abstract description 38
- 230000004044 response Effects 0.000 title claims abstract description 19
- 238000002360 preparation method Methods 0.000 title claims abstract description 11
- AOJJSUZBOXZQNB-TZSSRYMLSA-N Doxorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 AOJJSUZBOXZQNB-TZSSRYMLSA-N 0.000 claims abstract description 59
- 229960004679 doxorubicin Drugs 0.000 claims abstract description 26
- OYINILBBZAQBEV-UWJYYQICSA-N (17s,18s)-18-(2-carboxyethyl)-20-(carboxymethyl)-12-ethenyl-7-ethyl-3,8,13,17-tetramethyl-17,18,22,23-tetrahydroporphyrin-2-carboxylic acid Chemical compound N1C2=C(C)C(C=C)=C1C=C(N1)C(C)=C(CC)C1=CC(C(C)=C1C(O)=O)=NC1=C(CC(O)=O)C([C@@H](CCC(O)=O)[C@@H]1C)=NC1=C2 OYINILBBZAQBEV-UWJYYQICSA-N 0.000 claims abstract description 17
- 229920001223 polyethylene glycol Polymers 0.000 claims abstract description 16
- 238000000034 method Methods 0.000 claims abstract description 15
- 238000012986 modification Methods 0.000 claims abstract description 14
- 230000004048 modification Effects 0.000 claims abstract description 14
- 229940079593 drug Drugs 0.000 claims abstract description 11
- 239000002202 Polyethylene glycol Substances 0.000 claims abstract description 10
- XUIMIQQOPSSXEZ-UHFFFAOYSA-N Silicon Chemical compound [Si] XUIMIQQOPSSXEZ-UHFFFAOYSA-N 0.000 claims description 75
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 52
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 32
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 28
- 239000000377 silicon dioxide Substances 0.000 claims description 26
- 238000003756 stirring Methods 0.000 claims description 26
- 238000005406 washing Methods 0.000 claims description 23
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 22
- 239000000243 solution Substances 0.000 claims description 17
- 206010028980 Neoplasm Diseases 0.000 claims description 15
- 238000005576 amination reaction Methods 0.000 claims description 14
- 239000007853 buffer solution Substances 0.000 claims description 14
- 238000006243 chemical reaction Methods 0.000 claims description 14
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 12
- 238000001035 drying Methods 0.000 claims description 12
- 238000004108 freeze drying Methods 0.000 claims description 12
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 11
- 238000009210 therapy by ultrasound Methods 0.000 claims description 11
- BOTDANWDWHJENH-UHFFFAOYSA-N Tetraethyl orthosilicate Chemical compound CCO[Si](OCC)(OCC)OCC BOTDANWDWHJENH-UHFFFAOYSA-N 0.000 claims description 10
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 10
- WOWHHFRSBJGXCM-UHFFFAOYSA-M cetyltrimethylammonium chloride Chemical compound [Cl-].CCCCCCCCCCCCCCCC[N+](C)(C)C WOWHHFRSBJGXCM-UHFFFAOYSA-M 0.000 claims description 10
- 238000010438 heat treatment Methods 0.000 claims description 10
- 239000008367 deionised water Substances 0.000 claims description 7
- 229910021641 deionized water Inorganic materials 0.000 claims description 7
- LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide Substances CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 claims description 6
- FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 claims description 6
- NQTADLQHYWFPDB-UHFFFAOYSA-N N-Hydroxysuccinimide Chemical compound ON1C(=O)CCC1=O NQTADLQHYWFPDB-UHFFFAOYSA-N 0.000 claims description 6
- 239000006087 Silane Coupling Agent Substances 0.000 claims description 6
- 238000002835 absorbance Methods 0.000 claims description 6
- 239000012670 alkaline solution Substances 0.000 claims description 6
- 230000035484 reaction time Effects 0.000 claims description 6
- 238000001914 filtration Methods 0.000 claims description 5
- 239000000843 powder Substances 0.000 claims description 5
- 239000006228 supernatant Substances 0.000 claims description 5
- 238000001291 vacuum drying Methods 0.000 claims description 5
- 238000005303 weighing Methods 0.000 claims description 5
- WYTZZXDRDKSJID-UHFFFAOYSA-N (3-aminopropyl)triethoxysilane Chemical group CCO[Si](OCC)(OCC)CCCN WYTZZXDRDKSJID-UHFFFAOYSA-N 0.000 claims description 3
- HXLAEGYMDGUSBD-UHFFFAOYSA-N 3-[diethoxy(methyl)silyl]propan-1-amine Chemical compound CCO[Si](C)(OCC)CCCN HXLAEGYMDGUSBD-UHFFFAOYSA-N 0.000 claims description 3
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 claims description 3
- 235000011114 ammonium hydroxide Nutrition 0.000 claims description 3
- DBLXOVFQHHSKRC-UHFFFAOYSA-N ethanesulfonic acid;2-piperazin-1-ylethanol Chemical compound CCS(O)(=O)=O.OCCN1CCNCC1 DBLXOVFQHHSKRC-UHFFFAOYSA-N 0.000 claims description 3
- MQWFLKHKWJMCEN-UHFFFAOYSA-N n'-[3-[dimethoxy(methyl)silyl]propyl]ethane-1,2-diamine Chemical compound CO[Si](C)(OC)CCCNCCN MQWFLKHKWJMCEN-UHFFFAOYSA-N 0.000 claims description 3
- CWGFSQJQIHRAAE-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol tetrahydrochloride Chemical compound Cl.Cl.Cl.Cl.OCC(N)(CO)CO CWGFSQJQIHRAAE-UHFFFAOYSA-N 0.000 claims description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims 1
- 230000000694 effects Effects 0.000 abstract description 17
- 238000011068 loading method Methods 0.000 abstract description 6
- 230000005909 tumor killing Effects 0.000 abstract description 5
- 230000008901 benefit Effects 0.000 abstract description 4
- 238000001727 in vivo Methods 0.000 abstract description 4
- 230000008685 targeting Effects 0.000 abstract description 4
- 231100000331 toxic Toxicity 0.000 abstract description 3
- 230000002588 toxic effect Effects 0.000 abstract description 3
- BLRPTPMANUNPDV-UHFFFAOYSA-N Silane Chemical compound [SiH4] BLRPTPMANUNPDV-UHFFFAOYSA-N 0.000 abstract 1
- 239000002246 antineoplastic agent Substances 0.000 abstract 1
- 229940044683 chemotherapy drug Drugs 0.000 abstract 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 abstract 1
- 229910000077 silane Inorganic materials 0.000 abstract 1
- 238000003980 solgel method Methods 0.000 abstract 1
- 239000002105 nanoparticle Substances 0.000 description 19
- 239000000203 mixture Substances 0.000 description 11
- 210000004027 cell Anatomy 0.000 description 9
- 239000002953 phosphate buffered saline Substances 0.000 description 7
- 210000001519 tissue Anatomy 0.000 description 7
- 239000007864 aqueous solution Substances 0.000 description 5
- 239000003795 chemical substances by application Substances 0.000 description 5
- 230000002147 killing effect Effects 0.000 description 5
- 239000011148 porous material Substances 0.000 description 5
- 238000002604 ultrasonography Methods 0.000 description 5
- 238000005119 centrifugation Methods 0.000 description 4
- 238000009214 sonodynamic therapy Methods 0.000 description 4
- 230000009471 action Effects 0.000 description 3
- 238000002512 chemotherapy Methods 0.000 description 3
- 238000010586 diagram Methods 0.000 description 3
- 239000012528 membrane Substances 0.000 description 3
- 239000004005 microsphere Substances 0.000 description 3
- 239000003504 photosensitizing agent Substances 0.000 description 3
- 150000004032 porphyrins Chemical class 0.000 description 3
- 230000001502 supplementing effect Effects 0.000 description 3
- 210000004881 tumor cell Anatomy 0.000 description 3
- 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 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 description 2
- SWJRLTOYMKAFKN-UHFFFAOYSA-N azanium 2-(2,5-diphenyl-1H-tetrazol-1-ium-3-yl)-4,5-dimethyl-1,3-thiazole dibromide Chemical compound [Br-].[NH4+].CC=1N=C(SC1C)N1N([NH2+]C(=N1)C1=CC=CC=C1)C1=CC=CC=C1.[Br-] SWJRLTOYMKAFKN-UHFFFAOYSA-N 0.000 description 2
- 238000003795 desorption Methods 0.000 description 2
- 238000000502 dialysis Methods 0.000 description 2
- 238000004090 dissolution Methods 0.000 description 2
- 238000012377 drug delivery Methods 0.000 description 2
- 229920002674 hyaluronan Polymers 0.000 description 2
- 229960003160 hyaluronic acid Drugs 0.000 description 2
- 238000000338 in vitro Methods 0.000 description 2
- 230000014759 maintenance of location Effects 0.000 description 2
- 239000002245 particle Substances 0.000 description 2
- 238000001878 scanning electron micrograph Methods 0.000 description 2
- 238000001179 sorption measurement Methods 0.000 description 2
- 238000002560 therapeutic procedure Methods 0.000 description 2
- GJCOSYZMQJWQCA-UHFFFAOYSA-N 9H-xanthene Chemical compound C1=CC=C2CC3=CC=CC=C3OC2=C1 GJCOSYZMQJWQCA-UHFFFAOYSA-N 0.000 description 1
- 206010006187 Breast cancer Diseases 0.000 description 1
- 208000026310 Breast neoplasm Diseases 0.000 description 1
- DWGWCWDDNTVOGF-UHFFFAOYSA-N Cl.Cl.Cl.Cl.Cl.Cl Chemical compound Cl.Cl.Cl.Cl.Cl.Cl DWGWCWDDNTVOGF-UHFFFAOYSA-N 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 description 1
- 208000007536 Thrombosis Diseases 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 230000000274 adsorptive effect Effects 0.000 description 1
- 230000000259 anti-tumor effect Effects 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 239000011942 biocatalyst Substances 0.000 description 1
- 210000004204 blood vessel Anatomy 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 230000005779 cell damage Effects 0.000 description 1
- 208000037887 cell injury Diseases 0.000 description 1
- 230000003833 cell viability Effects 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- SURLGNKAQXKNSP-DBLYXWCISA-N chlorin Chemical compound C\1=C/2\N/C(=C\C3=N/C(=C\C=4NC(/C=C\5/C=CC/1=N/5)=CC=4)/C=C3)/CC\2 SURLGNKAQXKNSP-DBLYXWCISA-N 0.000 description 1
- 229930002868 chlorophyll a Natural products 0.000 description 1
- ATNHDLDRLWWWCB-AENOIHSZSA-M chlorophyll a Chemical compound C1([C@@H](C(=O)OC)C(=O)C2=C3C)=C2N2C3=CC(C(CC)=C3C)=[N+]4C3=CC3=C(C=C)C(C)=C5N3[Mg-2]42[N+]2=C1[C@@H](CCC(=O)OC\C=C(/C)CCC[C@H](C)CCC[C@H](C)CCCC(C)C)[C@H](C)C2=C5 ATNHDLDRLWWWCB-AENOIHSZSA-M 0.000 description 1
- 238000004737 colorimetric analysis Methods 0.000 description 1
- 238000013270 controlled release Methods 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 239000007857 degradation product Substances 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
- 238000013399 early diagnosis Methods 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 210000002919 epithelial cell Anatomy 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 238000001476 gene delivery Methods 0.000 description 1
- 230000036571 hydration Effects 0.000 description 1
- 238000006703 hydration reaction Methods 0.000 description 1
- 238000003384 imaging method Methods 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 238000002329 infrared spectrum Methods 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- 230000000302 ischemic effect Effects 0.000 description 1
- QDLAGTHXVHQKRE-UHFFFAOYSA-N lichenxanthone Natural products COC1=CC(O)=C2C(=O)C3=C(C)C=C(OC)C=C3OC2=C1 QDLAGTHXVHQKRE-UHFFFAOYSA-N 0.000 description 1
- 229920001427 mPEG Polymers 0.000 description 1
- 239000003094 microcapsule Substances 0.000 description 1
- 230000000877 morphologic effect Effects 0.000 description 1
- 239000002086 nanomaterial Substances 0.000 description 1
- 230000017074 necrotic cell death Effects 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 210000003463 organelle Anatomy 0.000 description 1
- 239000012466 permeate Substances 0.000 description 1
- 125000001484 phenothiazinyl group Chemical class C1(=CC=CC=2SC3=CC=CC=C3NC12)* 0.000 description 1
- 238000002428 photodynamic therapy Methods 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 238000005070 sampling Methods 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 238000006557 surface reaction Methods 0.000 description 1
- 230000002195 synergetic effect Effects 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- RZWIIPASKMUIAC-VQTJNVASSA-N thromboxane Chemical compound CCCCCCCC[C@H]1OCCC[C@@H]1CCCCCCC RZWIIPASKMUIAC-VQTJNVASSA-N 0.000 description 1
- 230000002792 vascular Effects 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K41/00—Medicinal preparations obtained by treating materials with wave energy or particle radiation ; Therapies using these preparations
- A61K41/0028—Disruption, e.g. by heat or ultrasounds, sonophysical or sonochemical activation, e.g. thermosensitive or heat-sensitive liposomes, disruption of calculi with a medicinal preparation and ultrasounds
- A61K41/0033—Sonodynamic cancer therapy with sonochemically active agents or sonosensitizers, having their cytotoxic effects enhanced through application of ultrasounds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7028—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages
- A61K31/7034—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin
- A61K31/704—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin attached to a condensed carbocyclic ring system, e.g. sennosides, thiocolchicosides, escin, daunorubicin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
- A61K47/56—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule
- A61K47/59—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes
- A61K47/60—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes the organic macromolecular compound being a polyoxyalkylene oligomer, polymer or dendrimer, e.g. PEG, PPG, PEO or polyglycerol
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/69—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit
- A61K47/6921—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit the form being a particulate, a powder, an adsorbate, a bead or a sphere
- A61K47/6923—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit the form being a particulate, a powder, an adsorbate, a bead or a sphere the form being an inorganic particle, e.g. ceramic particles, silica particles, ferrite or synsorb
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Epidemiology (AREA)
- Engineering & Computer Science (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Oncology (AREA)
- Ceramic Engineering (AREA)
- Inorganic Chemistry (AREA)
- Molecular Biology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
Abstract
本发明涉及一种声响应型载药棒状介孔硅及其制备方法与应用,属于生物医学工程领域。该方法为先采用溶胶凝胶法制备了介孔硅,接着用硅烷偶联物进行表面氨基修饰,随后进行聚乙二醇修饰,最后将声敏剂二氢卟吩e6(Ce6)与化疗药物阿霉素(DOX)负载于介孔硅上。采用该方法所制备的载药系统具有强大的肿瘤杀伤作用,并且也具有良好的生物利用度与体内循环时间。这避免了由于阿霉素不具有靶向作用而导致的生物毒性,降低了阿霉素的毒副作用。本发明所制备的一种声响应型载药棒状介孔硅形状、孔径均一,热稳定性好,具有良好的生物相容性,大的载药量与缓慢的药物释放速度。
Description
技术领域
本发明属于生物医学工程领域,具体涉及一种声响应型载药棒状介孔硅(MSNs)及其制备方法与应用。
背景技术
在各种无机纳米材料中,介孔二氧化硅纳米颗粒因其具有广泛的比表面积和孔体积、可调节的尺寸和形状等有利的形态特征而受到研究人员的广泛关注。他易于表面功能化,具有吸引人的物理化学性质,如丰富的表面化学性质、胶体稳定性和高分散性。纳米二氧化硅微球具有独特的拓扑结构,表面和内部都具有多孔结构,这使得纳米二氧化硅微球具有优异的性能。这些理想的特性在催化、聚合物填料、吸附、光学器件和生物医学的多种应用中具有特殊的意义,如生物成像、生物催化剂、生物传感、组织工程,以及靶向和控释的药物/蛋白质/基因传递系统。
声动力疗法(sonodynamic therapy,SDT)是在光动力疗法基础上发展而来,单独超声波对肿瘤组织具有一定的杀伤力,口服或者静脉注射声敏剂后,联合使用一定频率的超声辐照,杀伤效力明显增强,能够显著地诱导细胞损伤。声敏剂是SDT的关键环节,分为卟啉类及其衍生物,氧杂蒽类,吩噻嗪类化合物等。由于大部分卟啉类声敏剂的水溶性差,且容易被机体代谢,只有小部分到达肿瘤组织。无法产生有效的治疗活性,这极大地制约了SDT的应用。二氢卟吩e6通常可由属于叶绿素a的降解物,是一种良好的光敏剂,目前已经用于光敏剂应用于光动力领域。SDT研究中所用的声敏剂多数来源于光敏剂,二氢卟吩e6产生单线态氧的效率很高,所以适合开发用于肿瘤的声动力治疗。但同迄今为止的大部分声敏剂一样,二氢卟吩e6表现为疏水性,并在溶液中容易聚集,因此在实际应用中有一定困难。纳米颗粒是利用纳米技术制备的纳米级微粒或微囊,具有靶向性,载药量高及体内留存时间长等优点,是声敏剂的良好载体。纳米颗粒能改善声敏剂的疏水性,优化SDT的靶向治疗,药物转运,多模态成像及早期诊断,将纳米颗粒用于声动力疗法能发挥协同作用显著增强其抗肿瘤效应,并有望用于临床。
发明内容
本发明就构建了一种声响应型载药棒状介孔硅及其制备方法,并将其用于生物医学领域,采用本发明方法所制备的载药系统具有强大的肿瘤杀伤作用,并且也具有良好的生物利用度与体内循环时间。这避免了由于阿霉素不具有靶向作用而导致的生物毒性,降低了阿霉素的毒副作用。
本发明要解决的问题是,将二氢卟吩e6与阿霉素负载于PEG修饰的棒状介孔硅上后,通过将化疗与声动力疗法相结合,增强对肿瘤的杀伤作用。由于纳米介孔硅的高渗透长滞留效应(EPR),纳米粒更容易渗透进入肿瘤组织并长期滞留(和正常组织相比),这使得在肿瘤部位纳米粒富集,肿瘤部位药物浓度高,也减轻了其在其余部位的分布,在增强作用的同时降低了阿霉素的毒副作用。PEG修饰后,能够使得其体内循环时间增长,避免较快的被清除出体外。负载二氢卟吩e6后,在超声作用下产生非常多的单线氧,从肿瘤细胞夺取电子破坏肿瘤细胞的细胞器造成肿瘤细胞的死亡,同时破坏肿瘤血管上皮细胞使之释放血栓素,在肿瘤血管内形成血栓造成肿瘤组织的缺血性坏死,从而达到准确、彻底杀灭肿瘤的目的,而不损伤正常细胞。
本发明是通过以下技术方案来实现的:
一种声响应型载药棒状介孔硅的制备方法,包括如下步骤:
(1)棒状介孔硅的制备方法:将十六烷基三甲基氯化铵与水、碱性溶液加热搅拌反应,然后加入正硅酸乙酯,继续搅拌反应,反应结束后,进行离心,乙醇洗涤数次,水洗后置于真空干燥箱干燥,待干燥完成后转移至马弗炉中干燥,得到介孔硅;
(2)棒状介孔硅的氨基化修饰:将步骤(1)得到的介孔硅第一次加入异丙醇,超声,再向其中第二次加入异丙醇,加入硅烷偶联剂,加热搅拌,搅拌完成后离心,异丙醇洗涤,冻干,得到氨基化修饰的介孔硅;
(3)棒状介孔硅的聚乙二醇修饰:将mPEG-COOH加入去离子水中,溶解后加入1-乙基-(3-二甲基氨基丙基)碳酰二亚胺盐酸盐与N-羟基丁二酰亚胺,在常温下反应结束后,加入氨基化修饰的介孔硅,常温搅拌,离心,水洗数次后进行冷冻干燥,得到PEG修饰的介孔硅;
(4)载药方法:将聚乙二醇修饰的介孔硅加入到缓冲溶液,接着加入阿霉素与二氢卟吩e6的二甲基亚砜溶液,搅拌,离心,水洗数次,冻干后得到粉末,最终获得声响应型载药棒状介孔硅,精密称取载阿霉素与二氢卟吩e6介孔硅分散在水里,超声,离心后上清液过滤,测吸光度。
上述方法中,步骤(1)所述碱性溶液为NaOH溶液或氨水;所述加热的温度为70~90℃;所述加热的时间为0.5~1.5h;所述继续搅拌反应的时间为1.5~2.5h;所述正硅酸乙酯加入速度为0.03~0.05ml/s。十六烷基三甲基氯化铵、水、碱性溶液的摩尔比为1:(7.35~10.29):(2~2.6)。
上述方法中,步骤(2)中,所述硅烷偶联剂为3-氨丙基三乙氧基硅烷、γ-氨丙基甲基二乙氧基硅烷、N-2-氨乙基-3-氨丙基甲基二甲氧基硅烷;所述加热的温度为70~90℃步骤;步骤(1)所述继续搅拌反应的时间为20~28h;所述硅烷偶联剂与醇的体积比值为1:(25~75)。
上述方法中,步骤(3)中,所述mPEG-COOH(MW:2000)、1-乙基-(3-二甲基氨基丙基)碳酰二亚胺盐酸盐、N-羟基丁二酰亚胺的摩尔比值为1:(1~2):(1~2)。
上述方法中,步骤(3)中,所述反应的时间为0.5-1.5h;所述搅拌的时间为20-28h;所述mPEG-COOH与氨基化修饰的介孔硅的质量比为(4-8):1。
上述方法中,步骤(4)中,所述缓冲液为PBS缓冲液、HEPES(4-羟乙基哌嗪乙磺酸)缓冲液或Tris-HCl三羟甲基氨基甲烷盐酸盐缓冲液;所述缓冲液的pH值为7.2-7.4。
上述方法中,步骤(4)所述Ce6与阿霉素溶解于二甲基亚砜中;步骤(4)所述阿霉素二甲基亚砜溶液的浓度与PEG修饰的棒状介孔硅浓度(mg/mL)的比值为(5~7):1;所述二氢卟吩e6二甲基亚砜溶液的浓度与PEG修饰后的棒状介孔硅浓度(mg/mL)的比值为(5~7):1;所述离心速度为10000~12000rpm。
一种声响应型载药棒状介孔硅,所述声响应型载药棒状介孔硅应用形状、孔径均一,热稳定性好,具有良好的生物相容性,声响应性、大的载药量与缓慢的药物释放速度。载药后其大大增加了二氢卟吩e6的水溶性与稳定性,纳米粒进入体内后富集于肿瘤组织,在超声作用下发挥其肿瘤杀伤作用。
一种载阿霉素与二氢卟吩e6的棒状介孔硅。
上述声响应型载药棒状介孔硅用于生物医学中。
本发明与现有技术相比,具有如下有益效果:
(1)本发明所制备的一种声响应型载药棒状介孔硅形状、孔径均一,热稳定性好,具有良好的生物相容性,大的载药量与缓慢的药物释放速度。
(2)本发明所制备的一种声响应型载药棒状介孔硅在低强度超声作用下能够发挥强大的肿瘤杀伤作用。
(3)本发明提供了一种一种声响应型载药棒状介孔硅的制备方法,与先前的专利进行对比,将声敏剂负载于纳米粒上后,能够在低强度超声作用下协同化疗发挥肿瘤杀伤作用。是一种无创的治疗方式。
附图说明
图1为棒状介孔硅的SEM图。
图2为棒状介孔硅的SEM图。
图3为棒状介孔硅的红外光谱图。
图4为棒状介孔硅的直径分布图。
图5为棒状介孔硅的长度分布图。
图6为棒状介孔硅的N2吸附脱附曲线图。
图7为棒状介孔硅的孔径图。
图8为棒状介孔硅的释药。
图9为细胞活性图。
具体实施方式
以下结合附图和实例对本发明的具体实施作进一步说明,但本发明的实施和保护不限于此。需指出的是,以下若有未特别详细说明之过程,均是本领域技术人员可参照现有技术实现或理解的。所用试剂或仪器未注明生产厂商者,视为可以通过市售购买得到的常规产品。
实施例1
(1)介孔硅的制备方法:将1mL十六烷基三甲基氯化铵(CTAC)水溶液(25wt%inH2O的CTAC水溶液,约0.756mol/L)与120mL的水、0.876mL 2M的NaOH水溶液在80℃下搅拌1h,后以0.04ml/s的速度加入1mL的正硅酸乙酯(98%的TEOS溶液4.388mol/L),反应两小时后,进行离心,乙醇洗2次,水洗2次后置于真空干燥箱干燥,待干燥完成后转移至马弗炉,600℃干燥5h,得到介孔硅;
(2)介孔硅的氨基化修饰:将0.2g介孔硅加入20ml异丙醇超声20min,将异丙醇补充至100mL,加入2mL 98%3-氨丙基三乙氧基硅烷,80℃下搅拌24h,离心,异丙醇洗数次,冻干,得到氨基化修饰的介孔硅;
(3)介孔硅的聚乙二醇修饰:将0.6g的mPEG-COOH(甲氧基PEG羧基)加入去离子水中,完全溶解后加入86.26mg1-乙基-(3-二甲基氨基丙基)碳酰二亚胺盐酸盐与51.8mgN-羟基丁二酰亚胺,在常温下反应1h,反应结束后,随后加入100mg氨基化修饰的介孔硅,常温搅拌24h,离心,水洗2次后进行冷冻干燥,得到透明质酸修饰的介孔硅。
(4)载药方法:将5mg聚乙二醇修饰的介孔硅加入到5ml pH7.2 PBS溶液中,接着加入1ml 6mg/ml阿霉素与二氢卟吩e6的二甲基亚砜溶液,搅拌过夜,以12000rpm的速度离心,水洗数次,冻干后得到粉末,最终获得载阿霉素与Ce6介孔硅。精密称取10.0mg载阿霉素与Ce6介孔硅分散在10mL的去离子水里,超声30min,离心后上清液用0.22um的微孔滤膜过滤下,用紫外分光光度计在480nm处测吸光度。
载药率%=(声响应性棒状介孔硅里DOX的质量/声响应性棒状介孔硅质量)×100%
实施例2
将1mL十六烷基三甲基氯化铵(CTAC)水溶液(25wt%in H2O的CTAC水溶液,约0.756mol/L)与140mL的水、0.784mL 2.5M的NaOH水溶液在85℃下搅拌0.5h,后以0.05ml/s的速度加入1.14mL的正硅酸乙酯(98%的TEOS溶液4.388mol/L),反应1.5小时后,进行离心,乙醇洗2次,水洗2次后置于真空干燥箱干燥,待干燥完成后转移至马弗炉,550℃干燥5h,得到介孔硅。
(2)介孔硅的氨基化修饰:将0.4g介孔硅加入25ml异丙醇超声20min,将异丙醇补充至100ml,加入4ml 97%γ-氨丙基甲基二乙氧基硅烷,75℃下搅拌28h,离心,异丙醇洗数次,冻干,得到氨基化修饰的介孔硅。
(3)介孔硅的聚乙二醇修饰:将0.6g的mPEG-COOH加入quliz中,水合完全后加入115mg1-乙基-(3-二甲基氨基丙基)碳酰二亚胺盐酸盐与69mgN-羟基丁二酰亚胺,在常温下反应0.5h,反应结束后加入150mg氨基化修饰的介孔硅,常温搅拌28h,离心,水洗2次后进行冷冻干燥,得到透明质酸修饰的介孔硅。
(4)载药方法:将5mg聚乙二醇修饰的介孔硅加入到5ml pH7.3 HEPES(4-羟乙基哌嗪乙磺酸)缓冲液中,接着加入1ml 7mg/ml阿霉素与二氢卟吩e6的二甲基亚砜溶液,搅拌过夜,以10000rpm的速度离心,水洗数次,冻干后得到粉末,最终获得载阿霉素与Ce6介孔硅。精密称取10.0mg载阿霉素与Ce6介孔硅分散在10mL的去离子水里,超声30min,离心后上清液用0.22um的微孔滤膜过滤下,用紫外分光光度计在480nm处测吸光度。
载药率%=(声响应性棒状介孔硅里DOX的质量/声响应性棒状介孔硅质量)×100%
实施例3
将1mL十六烷基三甲基氯化铵(CTAC)水溶液(25wt%in H2O的CTAC水溶液,约0.756mol/L)与100mL的水、1mL 1.5M的氨水在75℃下搅拌1.5h,以0.03ml/s后加入0.85mL的正硅酸乙酯(98%的TEOS溶液4.388mol/L),反应2.5小时后,进行离心,乙醇洗2次,水洗2次后置于真空干燥箱干燥,待干燥完成后转移至马弗炉,575℃干燥5h,得到介孔硅。
(2)介孔硅的氨基化修饰:将0.13g介孔硅加入20ml异丙醇超声10min,将异丙醇补充至100ml,加入96%1.3ml N-2-氨乙基-3-氨丙基甲基二甲氧基硅烷,77.5℃下搅拌20h,离心,异丙醇洗数次,冻干,得到氨基化修饰的介孔硅。
(3)介孔硅的聚乙二醇修饰:将0.6g的mPEG-COOH加入去离子水中,完全溶解后加入58mg1-乙基-(3-二甲基氨基丙基)碳酰二亚胺盐酸盐与34.5mgN-羟基丁二酰亚胺,在常温下反应1.5h,反应结束后加入75mg氨基化修饰的介孔硅,常温搅拌20h,离心,水洗2次后进行冷冻干燥,得到透明质酸修饰的介孔硅。
(4)载药方法:将5mg聚乙二醇修饰的介孔硅加入到5ml pH7.4 Tris-HCl(三羟甲基氨基甲烷盐酸盐)缓冲液中,接着加入1ml 5mg/ml阿霉素与二氢卟吩e6的二甲基亚砜溶液,搅拌过夜,以11000rpm的速度离心,水洗数次,冻干后得到粉末,最终获得载阿霉素与Ce6介孔硅。精密称取10.0mg载阿霉素与二氢卟吩e6介孔硅分散在10mL的去离子水里,超声30min,离心后上清液用0.22um的微孔滤膜过滤下,用紫外分光光度计在480nm处测吸光度。
载药率%=(声响应性棒状介孔硅里DOX的质量/声响应性棒状介孔硅质量)×100%
图1为实施例1所得纳米粒在200nm标尺视野下的形态,呈棒状,粒径分布均一。
图2为实施例1所得纳米粒在100nm标尺视野下的形态,呈棒状,粒径分布均一。
图3为实施例1所得纳米粒的红外图谱,具有介孔硅的特征吸收峰。
图4为实施例1所得纳米粒的直径分布图,其直径分布较为均匀,大部分在120~130nm之间。
图5为实施例1所得纳米粒的长度分布图,其长度分布较为均匀,大部分在300nm之间。
图6为实施例1所得纳米粒的氮气脱吸附曲线,能够看到iv型吸附等温线,证实了其介孔结构。
图7为实施例1所得纳米粒的孔径分布图,能够看到其平均孔径在3nm左右,证实了其介孔结构。
药物释放的能力:采用透析法检测载药系统中DOX的体外释放曲线。简单地说,释放是在磷酸缓冲盐溶液(PBS,pH值为7.4)中进行的。将声响应性棒状介孔硅以10mg/mL的终浓度分散在PBS中,分别封装在透析袋(分子量截止值[MWCO]10000kDa)中,并在37℃和100rpm搅拌下浸入100mL PBS中。在预定的采样时间(2h、4h、6h、8h、10h、12h、24h、36h、48h),采集3mL样品,并添加等量的新鲜PBS。然后,对提取的样品进行过滤、稀释,并在480nm处用UVevis分光光度计(紫外分光光度计)进行分析。
图8分别为实施例1所得声响应型棒状介孔硅的阿霉素体外释放图。由图可知,其释放速度较为缓慢。
细胞活性测试:采用3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四唑溴化铵(MTT)比色法测定细胞活力。将细胞分为空白组(完全培养基组)、100ug/ml MSNs组、1ug/ml DOX组、不超声+声响应型棒状介孔硅(其中DOX的含量为1ug/ml)、超声+声响应型棒状介孔硅(其中DOX的含量为1ug/ml)组,每组设置三个平行孔。超声条件为0.6W/cm2,60s。4T1细胞以8×103的量接种在96孔板中,细胞贴壁后,空白组与实验组处理24小时,移除培养基并用MTT(噻唑蓝)溶液(0.5mg/mL)在37℃下培养4小时后,100μL二甲基亚砜溶解甲赞晶体,并使用微孔板读取器(Cytation 5,Biotek,USA)在490nm处测量吸光度。
图9为声响应型棒状介孔硅处理的细胞活性图。由图9可知声响应型棒状介孔硅轻微增强了阿霉素的肿瘤杀伤作用,在经过超声处理后,细胞的活性进一步降低。这说明化疗与声动力疗法相结合能够协同杀伤乳腺癌细胞。
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 (2)
1.一种用于治疗肿瘤的声响应型载药棒状介孔硅,其特征在于,所述声响应型载药棒状介孔硅的制备方法,包括如下步骤:
(1)棒状介孔硅的制备方法:将十六烷基三甲基氯化铵与水、碱性溶液加热搅拌反应,然后加入正硅酸乙酯,继续搅拌反应,反应结束后,进行离心,乙醇洗涤数次,水洗后置于真空干燥箱干燥,待干燥完成后转移至马弗炉中干燥,得到介孔硅;
(2)棒状介孔硅的氨基化修饰:将步骤(1)得到的介孔硅第一次加入异丙醇,超声,再向其中第二次加入异丙醇,加入硅烷偶联剂,加热搅拌,搅拌完成后离心,异丙醇洗涤,冻干,得到氨基化修饰的介孔硅;
(3)棒状介孔硅的聚乙二醇修饰:将mPEG-COOH加入去离子水中,溶解后加入1-乙基-(3-二甲基氨基丙基)碳酰二亚胺盐酸盐与N-羟基丁二酰亚胺,在常温下反应结束后,加入氨基化修饰的介孔硅,常温搅拌,离心,水洗数次后进行冷冻干燥,得到PEG修饰的介孔硅;
(4)载药方法:将PEG修饰的介孔硅加入到缓冲溶液,接着加入阿霉素与二氢卟吩e6的二甲基亚砜溶液,搅拌,离心,水洗数次,冻干后得到粉末,最终获得声响应型载药棒状介孔硅,精密称取载阿霉素与二氢卟吩e6介孔硅分散在水里,超声,离心后上清液过滤,测吸光度;
步骤(1)所述碱性溶液为NaOH溶液或氨水;所述加热的温度为70~90℃;所述加热的时间为0.5~1.5h;所述继续搅拌反应的时间为1.5~2.5h;所述正硅酸乙酯加入速度为0.03~0.05ml/s;所述十六烷基三甲基氯化铵、水、碱性溶液的摩尔比为1:(7.35~10.29):(2~2.6);
步骤(2)中,所述硅烷偶联剂为3-氨丙基三乙氧基硅烷、γ-氨丙基甲基二乙氧基硅烷、N-2-氨乙基-3-氨丙基甲基二甲氧基硅烷;所述加热的温度为70~90℃;步骤(2)中,所述搅拌反应的时间为20~28h;所述硅烷偶联剂与异丙醇的体积比值为1:(25~75);
步骤(3)中,所述mPEG-COOH、1-乙基-(3-二甲基氨基丙基)碳酰二亚胺盐酸盐、N-羟基丁二酰亚胺的摩尔比值为1:(1~2):(1~2);
步骤(3)中,所述反应的时间为0.5-1.5h;所述搅拌的时间为20-28h;所述mPEG-COOH与氨基化修饰的介孔硅的质量比为(4-8):1;
步骤(4)中,所述缓冲液为PBS缓冲液、HEPES(4-羟乙基哌嗪乙磺酸)缓冲液或Tris-HCl三羟甲基氨基甲烷盐酸盐缓冲液;所述缓冲液的pH值为7.2-7.4;
步骤(4)所述阿霉素二甲基亚砜溶液的浓度与PEG修饰的棒状介孔硅浓度(mg/mL)的比值为(5~7):1;所述二氢卟吩e6二甲基亚砜溶液的浓度与PEG修饰后的棒状介孔硅浓度的比值为(5~7):1;所述离心速度为10000~12000rpm。
2.权利要求1所述声响应型载药棒状介孔硅在制备治疗肿瘤的药物中的用途。
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202111661894.5A CN114209852B (zh) | 2021-12-30 | 2021-12-30 | 一种声响应型载药棒状介孔硅及其制备方法与应用 |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202111661894.5A CN114209852B (zh) | 2021-12-30 | 2021-12-30 | 一种声响应型载药棒状介孔硅及其制备方法与应用 |
Publications (2)
Publication Number | Publication Date |
---|---|
CN114209852A CN114209852A (zh) | 2022-03-22 |
CN114209852B true CN114209852B (zh) | 2024-02-09 |
Family
ID=80707295
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN202111661894.5A Active CN114209852B (zh) | 2021-12-30 | 2021-12-30 | 一种声响应型载药棒状介孔硅及其制备方法与应用 |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN114209852B (zh) |
Families Citing this family (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN115364211B (zh) * | 2022-08-02 | 2023-12-22 | 北京大学 | 超小酞菁共轭介孔二氧化硅纳米粒子及其作为声敏剂的应用 |
Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN109044993A (zh) * | 2018-09-18 | 2018-12-21 | 华南理工大学 | 一种以核酸适配体靶向聚乙二醇修饰的介孔二氧化硅纳米粒及其制备方法 |
Family Cites Families (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
FR2981643B1 (fr) * | 2011-10-25 | 2013-12-27 | Commissariat Energie Atomique | Procede de preparation d'un materiau composite silicium/carbone, materiau ainsi prepare, et electrode notamment electrode negative, comprenant ce materiau. |
US20210015757A1 (en) * | 2019-07-18 | 2021-01-21 | Nano Targeting & Therapy Biopharma Inc | Drug delivery by pore-modified mesoporous silica nanoparticles |
-
2021
- 2021-12-30 CN CN202111661894.5A patent/CN114209852B/zh active Active
Patent Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN109044993A (zh) * | 2018-09-18 | 2018-12-21 | 华南理工大学 | 一种以核酸适配体靶向聚乙二醇修饰的介孔二氧化硅纳米粒及其制备方法 |
Non-Patent Citations (1)
Title |
---|
Therapeutic Effect of Doxorubicin-Chlorin E6-Loaded Mesoporous Silica Nanoparticles Combined with Ultrasound on Triple-Negative Breast Cancer;Peng Xu等;Int J Nanomedicine;第15卷;第2659-2668页摘要、材料和方法、结果、讨论部分 * |
Also Published As
Publication number | Publication date |
---|---|
CN114209852A (zh) | 2022-03-22 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
Kim et al. | Post-synthetic modifications in porous organic polymers for biomedical and related applications | |
CN107496377B (zh) | 一种中空介孔门控型透明质酸修饰的普鲁士蓝纳米粒载药体系的制备方法及应用 | |
CN107158405B (zh) | 一种线粒体靶向的纳米光敏免疫复合药物及其制备方法和应用 | |
EP1362598A1 (en) | Active oxygen generator containing photosensitizer for ultrasonic therapy | |
JP2013513609A5 (zh) | ||
WO2022077830A1 (zh) | 青蒿素及其衍生物在制备热动力治疗敏化剂中的应用 | |
CN114209852B (zh) | 一种声响应型载药棒状介孔硅及其制备方法与应用 | |
Hu et al. | Dynamic nanoassembly-based drug delivery system (DNDDS): learning from nature | |
CN105126121B (zh) | 一种靶向金银合金纳米笼的药物递送系统的制备方法及应用 | |
Zhang et al. | Co-delivery of rose bengal and doxorubicin nanoparticles for combination photodynamic and chemo-therapy | |
Chen et al. | Lactobionic acid-functionalized hollow mesoporous silica nanoparticles for cancer chemotherapy and phototherapy | |
CN109464676B (zh) | 一种壳寡糖光敏靶向纳米粒的制备方法及产品 | |
CN110448699B (zh) | 包含功能性多肽修饰七甲川花菁素类染料的肿瘤细胞核靶向载药纳米粒子及制备方法 | |
Kang et al. | Flexible human serum albumin nanocapsules to enhance drug delivery and cellular uptake for photodynamic/chemo cancer therapy | |
CN109568577B (zh) | 一种用作光/声敏剂的靶向纳米颗粒及其制备方法和应用 | |
CN106177948A (zh) | 一种包裹阿霉素的中空硅‑金星核/壳纳米材料的制备方法 | |
CN111110630B (zh) | 跨血脑屏障药物递送体系及其制备方法和应用 | |
Gooneh-Farahani et al. | A critical comparison study on the pH-sensitive nanocomposites based on graphene-grafted chitosan for cancer theragnosis | |
CN110251672B (zh) | 一种纳米诊疗剂及其制备方法与应用 | |
CN115364211B (zh) | 超小酞菁共轭介孔二氧化硅纳米粒子及其作为声敏剂的应用 | |
CN114225029B (zh) | 一种声敏响应的纳米颗粒及其应用 | |
CN113577277B (zh) | 一种PEOz和聚多巴胺-钆离子网络修饰的可降解介孔硅纳米给药系统及制备方法 | |
CN109806394B (zh) | 一种介孔二氧化硅药物递送系统及其应用 | |
CN113018276B (zh) | 一种增强声动力治疗的肺癌靶向自组装纳米药物及其制备与应用 | |
CN105949344B (zh) | 一种阳离子超支化多糖衍生物及其在增强血卟啉类光敏剂对肿瘤细胞光毒性方面的应用 |
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 |