CN107349432A - One kind load Sorafenib/siRNA mesoporous silicon oxide lactobionic acid targeted nano particle - Google Patents
One kind load Sorafenib/siRNA mesoporous silicon oxide lactobionic acid targeted nano particle Download PDFInfo
- Publication number
- CN107349432A CN107349432A CN201710562955.XA CN201710562955A CN107349432A CN 107349432 A CN107349432 A CN 107349432A CN 201710562955 A CN201710562955 A CN 201710562955A CN 107349432 A CN107349432 A CN 107349432A
- Authority
- CN
- China
- Prior art keywords
- sorafenib
- silicon oxide
- sirna
- mesoporous silicon
- lactobionic acid
- 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.)
- Granted
Links
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 title claims abstract description 63
- 108020004459 Small interfering RNA Proteins 0.000 title claims abstract description 62
- MLDQJTXFUGDVEO-UHFFFAOYSA-N BAY-43-9006 Chemical compound C1=NC(C(=O)NC)=CC(OC=2C=CC(NC(=O)NC=3C=C(C(Cl)=CC=3)C(F)(F)F)=CC=2)=C1 MLDQJTXFUGDVEO-UHFFFAOYSA-N 0.000 title claims abstract description 52
- 239000005511 L01XE05 - Sorafenib Substances 0.000 title claims abstract description 52
- 229960003787 sorafenib Drugs 0.000 title claims abstract description 52
- 239000002105 nanoparticle Substances 0.000 title claims abstract description 43
- 229940099563 lactobionic acid Drugs 0.000 title claims abstract description 38
- 229910052814 silicon oxide Inorganic materials 0.000 title claims abstract description 23
- UOQHWNPVNXSDDO-UHFFFAOYSA-N 3-bromoimidazo[1,2-a]pyridine-6-carbonitrile Chemical compound C1=CC(C#N)=CN2C(Br)=CN=C21 UOQHWNPVNXSDDO-UHFFFAOYSA-N 0.000 title claims abstract description 16
- 239000000377 silicon dioxide Substances 0.000 claims abstract description 20
- 238000005576 amination reaction Methods 0.000 claims abstract description 12
- 238000001179 sorption measurement Methods 0.000 claims abstract 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 26
- XUIMIQQOPSSXEZ-UHFFFAOYSA-N Silicon Chemical compound [Si] XUIMIQQOPSSXEZ-UHFFFAOYSA-N 0.000 claims description 20
- 229910052710 silicon Inorganic materials 0.000 claims description 20
- 239000010703 silicon Substances 0.000 claims description 20
- 239000003814 drug Substances 0.000 claims description 14
- 230000004048 modification Effects 0.000 claims description 14
- 238000012986 modification Methods 0.000 claims description 14
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 12
- 238000003756 stirring Methods 0.000 claims description 12
- 238000002360 preparation method Methods 0.000 claims description 11
- 235000019441 ethanol Nutrition 0.000 claims description 9
- 239000002253 acid Substances 0.000 claims description 7
- 239000002245 particle Substances 0.000 claims description 7
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 6
- 229940079593 drug Drugs 0.000 claims description 5
- WYTZZXDRDKSJID-UHFFFAOYSA-N (3-aminopropyl)triethoxysilane Chemical class CCO[Si](OCC)(OCC)CCCN WYTZZXDRDKSJID-UHFFFAOYSA-N 0.000 claims description 4
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-dimethylformamide Substances CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 4
- 238000004108 freeze drying Methods 0.000 claims description 4
- 238000005406 washing Methods 0.000 claims description 4
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical class CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 claims description 3
- 150000007513 acids Chemical class 0.000 claims description 3
- 238000001556 precipitation Methods 0.000 claims description 3
- 239000008367 deionised water Substances 0.000 claims description 2
- 229910021641 deionized water Inorganic materials 0.000 claims description 2
- 150000002500 ions Chemical class 0.000 claims description 2
- 238000011275 oncology therapy Methods 0.000 claims description 2
- 239000002904 solvent Substances 0.000 claims description 2
- 230000000694 effects Effects 0.000 abstract description 16
- 230000008878 coupling Effects 0.000 abstract description 3
- 238000010168 coupling process Methods 0.000 abstract description 3
- 238000005859 coupling reaction Methods 0.000 abstract description 3
- 231100000331 toxic Toxicity 0.000 abstract description 3
- 230000002588 toxic effect Effects 0.000 abstract description 3
- 239000002246 antineoplastic agent Substances 0.000 abstract 1
- 229940124597 therapeutic agent Drugs 0.000 abstract 1
- 210000004027 cell Anatomy 0.000 description 40
- 206010028980 Neoplasm Diseases 0.000 description 13
- 239000000243 solution Substances 0.000 description 13
- 201000011510 cancer Diseases 0.000 description 12
- MHMNJMPURVTYEJ-UHFFFAOYSA-N fluorescein-5-isothiocyanate Chemical compound O1C(=O)C2=CC(N=C=S)=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 MHMNJMPURVTYEJ-UHFFFAOYSA-N 0.000 description 12
- 238000001890 transfection Methods 0.000 description 8
- 235000015097 nutrients Nutrition 0.000 description 6
- 230000008685 targeting Effects 0.000 description 6
- 230000001093 anti-cancer Effects 0.000 description 5
- 230000000259 anti-tumor effect Effects 0.000 description 5
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 4
- 241000790917 Dioxys <bee> Species 0.000 description 4
- 101000600434 Homo sapiens Putative uncharacterized protein encoded by MIR7-3HG Proteins 0.000 description 4
- 102100037401 Putative uncharacterized protein encoded by MIR7-3HG Human genes 0.000 description 4
- -1 VEGFR- 2nd Proteins 0.000 description 4
- 235000013339 cereals Nutrition 0.000 description 4
- 238000006243 chemical reaction Methods 0.000 description 4
- 230000009368 gene silencing by RNA Effects 0.000 description 4
- 238000011068 loading method Methods 0.000 description 4
- 239000000463 material Substances 0.000 description 4
- 238000011282 treatment Methods 0.000 description 4
- 102000040650 (ribonucleotides)n+m Human genes 0.000 description 3
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
- 108091030071 RNAI Proteins 0.000 description 3
- 229910003978 SiClx Inorganic materials 0.000 description 3
- 230000004913 activation Effects 0.000 description 3
- 238000003782 apoptosis assay Methods 0.000 description 3
- 210000000481 breast Anatomy 0.000 description 3
- 201000010099 disease Diseases 0.000 description 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- 239000002086 nanomaterial Substances 0.000 description 3
- 238000012545 processing Methods 0.000 description 3
- 238000011160 research Methods 0.000 description 3
- 239000006228 supernatant Substances 0.000 description 3
- 206010059866 Drug resistance Diseases 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 2
- 241000209094 Oryza Species 0.000 description 2
- 235000007164 Oryza sativa Nutrition 0.000 description 2
- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 2
- 125000003277 amino group Chemical group 0.000 description 2
- 239000003005 anticarcinogenic agent Substances 0.000 description 2
- 230000004700 cellular uptake Effects 0.000 description 2
- 230000007547 defect Effects 0.000 description 2
- 238000013461 design Methods 0.000 description 2
- 238000009826 distribution Methods 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- RWSXRVCMGQZWBV-WDSKDSINSA-N glutathione Chemical compound OC(=O)[C@@H](N)CCC(=O)N[C@@H](CS)C(=O)NCC(O)=O RWSXRVCMGQZWBV-WDSKDSINSA-N 0.000 description 2
- 230000002401 inhibitory effect Effects 0.000 description 2
- 230000005764 inhibitory process Effects 0.000 description 2
- 239000008101 lactose Substances 0.000 description 2
- 108020004999 messenger RNA Proteins 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 108090000623 proteins and genes Proteins 0.000 description 2
- 235000009566 rice Nutrition 0.000 description 2
- 235000012239 silicon dioxide Nutrition 0.000 description 2
- 238000001228 spectrum Methods 0.000 description 2
- 230000002195 synergetic effect Effects 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- 231100000419 toxicity Toxicity 0.000 description 2
- 230000001988 toxicity Effects 0.000 description 2
- 210000004881 tumor cell Anatomy 0.000 description 2
- PRDFBSVERLRRMY-UHFFFAOYSA-N 2'-(4-ethoxyphenyl)-5-(4-methylpiperazin-1-yl)-2,5'-bibenzimidazole Chemical compound C1=CC(OCC)=CC=C1C1=NC2=CC=C(C=3NC4=CC(=CC=C4N=3)N3CCN(C)CC3)C=C2N1 PRDFBSVERLRRMY-UHFFFAOYSA-N 0.000 description 1
- FSPQCTGGIANIJZ-UHFFFAOYSA-N 2-[[(3,4-dimethoxyphenyl)-oxomethyl]amino]-4,5,6,7-tetrahydro-1-benzothiophene-3-carboxamide Chemical compound C1=C(OC)C(OC)=CC=C1C(=O)NC1=C(C(N)=O)C(CCCC2)=C2S1 FSPQCTGGIANIJZ-UHFFFAOYSA-N 0.000 description 1
- 101150075175 Asgr1 gene Proteins 0.000 description 1
- 201000009030 Carcinoma Diseases 0.000 description 1
- 206010010356 Congenital anomaly Diseases 0.000 description 1
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 1
- 108010040476 FITC-annexin A5 Proteins 0.000 description 1
- 108010024636 Glutathione Proteins 0.000 description 1
- 108700011259 MicroRNAs Proteins 0.000 description 1
- BELBBZDIHDAJOR-UHFFFAOYSA-N Phenolsulfonephthalein Chemical compound C1=CC(O)=CC=C1C1(C=2C=CC(O)=CC=2)C2=CC=CC=C2S(=O)(=O)O1 BELBBZDIHDAJOR-UHFFFAOYSA-N 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 108010039918 Polylysine Proteins 0.000 description 1
- 238000012228 RNA interference-mediated gene silencing Methods 0.000 description 1
- 102100020718 Receptor-type tyrosine-protein kinase FLT3 Human genes 0.000 description 1
- 101710151245 Receptor-type tyrosine-protein kinase FLT3 Proteins 0.000 description 1
- 208000006265 Renal cell carcinoma Diseases 0.000 description 1
- BOTDANWDWHJENH-UHFFFAOYSA-N Tetraethyl orthosilicate Chemical compound CCO[Si](OCC)(OCC)OCC BOTDANWDWHJENH-UHFFFAOYSA-N 0.000 description 1
- GSEJCLTVZPLZKY-UHFFFAOYSA-N Triethanolamine Chemical class OCCN(CCO)CCO GSEJCLTVZPLZKY-UHFFFAOYSA-N 0.000 description 1
- 108010053096 Vascular Endothelial Growth Factor Receptor-1 Proteins 0.000 description 1
- 108010053100 Vascular Endothelial Growth Factor Receptor-3 Proteins 0.000 description 1
- 102100033178 Vascular endothelial growth factor receptor 1 Human genes 0.000 description 1
- 102100033179 Vascular endothelial growth factor receptor 3 Human genes 0.000 description 1
- NJSVDVPGINTNGX-UHFFFAOYSA-N [dimethoxy(propyl)silyl]oxymethanamine Chemical compound CCC[Si](OC)(OC)OCN NJSVDVPGINTNGX-UHFFFAOYSA-N 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 230000000118 anti-neoplastic effect Effects 0.000 description 1
- 230000006907 apoptotic process Effects 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 150000001649 bromium compounds Chemical class 0.000 description 1
- 239000007853 buffer solution Substances 0.000 description 1
- 125000000609 carbazolyl group Chemical class C1(=CC=CC=2C3=CC=CC=C3NC12)* 0.000 description 1
- 230000004663 cell proliferation Effects 0.000 description 1
- 239000006285 cell suspension Substances 0.000 description 1
- 238000007385 chemical modification Methods 0.000 description 1
- 238000002512 chemotherapy Methods 0.000 description 1
- 239000002131 composite material Substances 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- 230000001186 cumulative effect Effects 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 230000000593 degrading effect Effects 0.000 description 1
- 238000002242 deionisation method Methods 0.000 description 1
- 230000006866 deterioration Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 238000012377 drug delivery Methods 0.000 description 1
- 230000009881 electrostatic interaction Effects 0.000 description 1
- 238000001976 enzyme digestion Methods 0.000 description 1
- CCIVGXIOQKPBKL-UHFFFAOYSA-N ethanesulfonic acid Chemical compound CCS(O)(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-N 0.000 description 1
- CWAFVXWRGIEBPL-UHFFFAOYSA-N ethoxysilane Chemical compound CCO[SiH3] CWAFVXWRGIEBPL-UHFFFAOYSA-N 0.000 description 1
- 125000005909 ethyl alcohol group Chemical group 0.000 description 1
- 238000000684 flow cytometry Methods 0.000 description 1
- 238000000799 fluorescence microscopy Methods 0.000 description 1
- 238000007710 freezing Methods 0.000 description 1
- 230000008014 freezing Effects 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- 229960003180 glutathione Drugs 0.000 description 1
- 239000003102 growth factor Substances 0.000 description 1
- 238000009396 hybridization Methods 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000011081 inoculation Methods 0.000 description 1
- 229920000592 inorganic polymer Polymers 0.000 description 1
- 229940043355 kinase inhibitor Drugs 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 201000007270 liver cancer Diseases 0.000 description 1
- 208000014018 liver neoplasm Diseases 0.000 description 1
- 238000002483 medication Methods 0.000 description 1
- 239000002609 medium Substances 0.000 description 1
- 238000000034 method Methods 0.000 description 1
- 239000002679 microRNA Substances 0.000 description 1
- 230000036457 multidrug resistance Effects 0.000 description 1
- 239000002773 nucleotide Substances 0.000 description 1
- 125000003729 nucleotide group Chemical group 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 229960003531 phenolsulfonphthalein Drugs 0.000 description 1
- 239000003757 phosphotransferase inhibitor Substances 0.000 description 1
- 229920000729 poly(L-lysine) polymer Polymers 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 229920000656 polylysine Polymers 0.000 description 1
- 239000002861 polymer material Substances 0.000 description 1
- 239000011148 porous material Substances 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- 208000002815 pulmonary hypertension Diseases 0.000 description 1
- 208000015347 renal cell adenocarcinoma Diseases 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 230000006641 stabilisation Effects 0.000 description 1
- 238000011105 stabilization Methods 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 238000013518 transcription Methods 0.000 description 1
- 230000035897 transcription Effects 0.000 description 1
- QQQSFSZALRVCSZ-UHFFFAOYSA-N triethoxysilane Chemical compound CCO[SiH](OCC)OCC QQQSFSZALRVCSZ-UHFFFAOYSA-N 0.000 description 1
- HNJXPTMEWIVQQM-UHFFFAOYSA-M triethyl(hexadecyl)azanium;bromide Chemical compound [Br-].CCCCCCCCCCCCCCCC[N+](CC)(CC)CC HNJXPTMEWIVQQM-UHFFFAOYSA-M 0.000 description 1
- 239000003643 water by type Substances 0.000 description 1
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
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7088—Compounds having three or more nucleosides or nucleotides
- A61K31/713—Double-stranded nucleic acids or oligonucleotides
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
-
- 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
- A61K47/26—Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
-
- 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
- A61K9/5115—Inorganic compounds
-
- 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
- A61K9/5123—Organic compounds, e.g. fats, sugars
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- General Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Optics & Photonics (AREA)
- Physics & Mathematics (AREA)
- Nanotechnology (AREA)
- Biomedical Technology (AREA)
- Biochemistry (AREA)
- Molecular Biology (AREA)
- Inorganic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention discloses the mesoporous silicon oxide lactobionic acid targeted nano particle of load Sorafenib/siRNA a kind of and its application on anti-cancer therapeutic agent is prepared.The targeted nano particle be by mesoporous silica nano-particle after surface amination is modified, Sorafenib is supported in its inner duct, by on lactobionic acid covalent coupling to its outer surface, and by electrostatic adsorption, siRNA is adsorbed onto its outer surface and formed.This medicine-carried system of the invention can not only improve siRNA stability, can also realize the target administration of Sorafenib, so as to effectively mitigate its toxic side effect to normal cell.
Description
Technical field
The invention belongs to antineoplastic preparation field, and in particular to one kind load Sorafenib/siRNA mesoporous dioxy
SiClx-lactobionic acid targeted nano particle and its application.
Background technology
In recent decades, the deterioration of global environment causes the incidence of disease more and more higher of cancer, the people for dying from cancer every year
Number is up to 8,800,000 people.At present, chemotherapy remains the main method for the treatment of cancer.However, the chemotherapeutics used in treating cancer is big
The defects of lacking targeting, Multidrug resistance and bioavailability are low all be present, these defects greatly limit them
Clinical practice；Thus novel Drug Delivery Systems are always the focus of medicine research.
Sorafenib is a kind of multiple kinase inhibitor that can target a variety of growth factor receptorses, including VEGFR-1, VEGFR-
2nd, VEGFR-3, PDGFR-b, c-KIT, FLT-3 and RET etc., its structural formula are：。
Sorafenib 2005 by FDA approvals to treat advanced renal cell cancer, and be unique a kind of by the complete of FDA approvals so far
The medicines resistant to liver cancer of body treatment.Although Sorafenib is showing the effect of stronger on clinical treatment, its side effect
Limit its further development and application to a certain extent with drug resistance.Therefore, exploitation one kind can reduce malicious secondary work
With with drug resistance, improve targeting Sorafenib preparation it is particularly important.
RNA is disturbed（RNA interference, RNAi）Refer to double-stranded RNA（Double-stranded RNA, dsRNA）
A kind of microRNA of 21-25 nucleotides is processed into via specific endonucleases Dicer（siRNA）, siRNA leads to
Cross and matched completely with said target mrna code area or UTR areas, said target mrna of degrading, cause silence after genetic transcription.RNAi technology has letter
The characteristics of any gene of single, quick, specific silence, it is set to be widely used for studying tumour, pulmonary hypertension, congenital hereditary
The target treatment of the diseases such as disease, and achieve certain achievement.But siRNA is easy to be degraded in the environment of serum, so that its
It is difficult to play its RNAi effects in cell.In addition, free siRNA cannot be introduced into cell, it is necessary to be chemically modified or
The load of person's nano particle can just be efficiently entering cells play effect.But in view of the siRNA of chemical modification may loss of activity, because
This, designs suitable carrier and is had been a great concern with improving siRNA therapeutic effect.
Mesopore silicon dioxide nano material is a kind of new inorganic polymer pharmaceutical carrier.It is mainly characterized by：（1）
Particle has great surface area and duct capacity, total specific surface area>900 m2/ g, pore capacities>0.9 cm3/ g, there is provided larger
Storage and reaction compartment；（2）Particle diameter can adjust, and easily be swallowed by tumour cell, without obvious cytology toxicity, external biological phase
Capacitive is good；（3）Between the nm of 2 nm~10, size can adjust in aperture, can adjust drugloading rate by changing aperture；（4）Have
Inner surface and outer surface, functional modification and then the excellent hybridization carrier of processability can be carried out.These characteristics make mesoporous dioxy
SiClx nano-particle possesses huge potential using value.
Lactobionic acid（LA）It is active biomolecule caused by lactose oxidation, its structural formula is：.Recent studies indicate that lactobionic acid can be with the mistake on cancer cell surfaces
The ASGPR receptor-specifics for crossing expression combine, and allow lactobionic acid to play the role of efficient target cancer cell.Therefore, lactose aldehyde
Acid has been a great concern in the delivery system research of anticarcinogen, it has also become the new focus of target cancer cell research.
2012, Hartonno, S.B. etc.（ACS Nano, volume 6, page 2104,2012）Synthesize large aperture（Aperture is more than
10nm）Silica nano particle, and it is left successfully to modify in particle exterior surface and duct electropositive high polymer material poly
Lysine PLL (Poly-L-Lysine) is revolved, and siRNA is adsorbed by electrostatic interaction and realizes that siRNA is disturbed, but this nanometer of medicine
Thing carrier conveying siRNA efficiency comparison is low, and particle possesses larger toxicity in low concentration, and biocompatibility is not high.Patent
CN 105056239A disclose a kind of mesoporous silicon oxide carrying medicament and siRNA composite and its preparation and prepared
Application in cancer therapy drug, by the way that using the mesoporous silicon oxide that carrying medicament acts on as core, surface passes through disulfide bond siRNA
Mesoporous closure is carried out, while plays a part of carrying medicament siRNA.The nano material can pass through cancer cell after entering cell
The glutathione response of interior high expression causes disulfide bonds while discharges medicine and siRNA, improves siRNA stabilization
Property, biocompatibility is preferable, but it does not have good targeting before cancer cell is entered, it is impossible to improves cancer cell and this is received
The intake of rice material.In addition, patent CN 104027821A provide a kind of conveying siRNA nano particle, it is in mesoporous dioxy
The surface modification of SiClx polyethylene glycol and peptide molecule, not only increase biocompatibility, and greatly improve siRNA
Interference effect.But it is similar to the A of patent CN 105056239, due to the shortage of targeted molecular, contain the nanometer material of medicine
Material can not be realized in the highly enriched of tumor cell surface, it is impossible to obtain the effect of optimal.
The content of the invention
It is an object of the invention to provide a kind of the mesoporous of Sorafenib/siRNA is loaded with target anticancer effect
Silica-lactobionic acid drug-loading nanoparticles, it by siRNA by being adsorbed onto mesoporous silicon oxide outer surface, to improve
SiRNA stability, and the targeting using lactobionic acid to cancer cell, improve the antitumor activity of Sorafenib.
To achieve the above object, the present invention adopts the following technical scheme that：
One kind load Sorafenib/siRNA mesoporous silicon oxide-lactobionic acid targeted nano particle, its preparation method include
Following steps：
1）Prepare the mesoporous silica nano-particle that particle diameter is about 100nm（MSN）；
2）Gained mesoporous silica nano-particle is dissolved in absolute ethyl alcohol, adds the 3- aminopropyls of nanoparticle weight 0.4%
Triethoxysilane, centrifuged after 12h is stirred at room temperature, wash, be freeze-dried through ethanol, obtain the mesoporous dioxy of surface amino groups modification
SiClx nano particle（MSN-NH2）；
3）By gained MSN-NH2Dissolving in acetone, adds Sorafenib after stirring 1 h at room temperature, is stirred for 30min, then
30 min, abandoning supernatant are centrifuged under 13000rpm, gained precipitation is washed with deionized, is freeze-dried, produces load rope
La Feini mesoporous silica nano-particle（SO@MSN）；Wherein, the mesoporous silicon oxide and Suo Lafei after amination modification
The weight ratio of Buddhist nun is 3:2；
4）Using DMF as solvent, SO@MSN, EDC and NHS are added（Three's weight ratio is 3:10:4）, at room temperature
After stirring 4h, by volume 4:1 adds the lactobionic acid solution that mass concentration is 2%, continues to stir 12h, is then centrifuged for, through going
It is freeze-dried after ion water washing, mesoporous silicon oxide-lactobionic acid nano particle of load Sorafenib is made（SO@MSN-
LA）；
5）SO@MSN-LA are added in acetone, ultrasonic disperse 10min, then by mass volume ratio 1:3 g/L are added in the solution
SiRNA, 20min is stirred, produces the targeted nano particle（SO/siRNA@MSN-LA）.
Step 4）Described in lactobionic acid solution be by 40 mg lactobionic acids, 100 mg dichloroethanes and 0.1 mol MES
（pH=6）24 h are stirred at room temperature to be made.
In view of the deficiencies in the prior art, the present invention loads to Sorafenib in the inner duct of mesoporous silicon oxide, and leads to
Cross covalent bond and lactobionic acid is coupled to mesoporous silicon oxide outer surface, acted on finally by electrostatic charge and be adsorbed onto siRNA
Mesoporous silicon oxide outer surface.This aspect improves siRNA stability and the biocompatibility of drug-loading system, and it can be entered
Enter and play one's part to the full into the cell；On the other hand, the efficient target anticancer effect of lactobionic acid can also improve Sorafenib
Antitumous effect.Therefore, present invention gained targeted nano particle can be used for the targeted drug that oncotherapy is made.
The advantage of the invention is that：
1st, the present invention can significantly increase siRNA stability, it is heavy to improve it using mesoporous silicon oxide as siRNA carrier
The efficiency of silent gene；
2nd, the present invention uses lactobionic acid as targeted molecular, Sorafenib can be made to be enriched with carcinoma cells, and can significantly improve
Cell, so that while Sorafenib antitumous effect is improved, reduces Sorafenib to normal group to the uptake ratio of medicine
The toxic side effect knitted；
3rd, the nano medicament carrying system constructed by the present invention is also applied for that other toxic side effects in addition to Sorafenib are big or indissoluble
The anticarcinogen of property；
4th, medicine-carried system preparation method designed by the present invention is simple, material is easy to get, and is advantageous to further expand and prepares yield.
Brief description of the drawings
Fig. 1 is the mesoporous silica nano-particle prepared by embodiment 1（MSN）TEM figure.
Fig. 2 is mesoporous silicon oxide-lactobionic acid of the load Sorafenib prepared by embodiment 4（SO@MSN-LA）'s
Grain size distribution.
Fig. 3 is mesoporous silicon oxide（MSN）, surface amination modification mesoporous silicon oxide（MSN-NH2）, activation breast
Uronic acid（LA）With mesoporous silicon oxide-lactobionic acid of load Sorafenib（SO@MSN-LA）Infrared absorpting light spectra.
Fig. 4 is mesoporous silicon oxide（MSN）, surface amination modification mesoporous silicon oxide（MSN-NH2）With load rope
La Feini mesoporous silicon oxide-lactobionic acid（SO@MSN-LA）Zeta electric potential figure.
Fig. 5 is the preparation versus time curve of Sorafenib in different medicine-carried systems.
Fig. 6 is the result of MTT experiment in embodiment 7.
Fig. 7 is the result that Apoptosis assay is tested in embodiment 8.
Fig. 8 is the result that cellular uptake is tested in embodiment 9.
Fig. 9 is the result of cell transfection assays in embodiment 10, and wherein A is the design sketch in fluorescence off field, and B turns for cell
Dye rate.
Embodiment
In order that content of the present invention easily facilitates understanding, with reference to embodiment to of the present invention
Technical scheme is described further, but the present invention is not limited only to this.
The synthesis of the mesoporous silica nano-particle of embodiment 1
Add 2 g cetyltriethylammonium bromides, 0.1 g triethanolamines and 20 mL deionized waters in reaction bulb, 95 DEG C
1 h of lower reaction；Then the mL of tetraethyl orthosilicate 1.5 is added dropwise in 20-30 min, finishes after continuing to react at 95 DEG C
1h；React and centrifuged 15 min after 12000 rpm at room temperature, obtained mesopore silicon dioxide nano material crude product, use deionization
Water and absolute ethyl alcohol are washed twice respectively, and gained solid is suspended in acidic ethanol（Concentrated hydrochloric acid：Absolute ethyl alcohol=5:1, V:V）,
24 h flow back to remove unreacted cetyltriethylammonium bromide, centrifuges, is washed with deionized, -50 DEG C of freezings are dry
It is dry, obtain mesoporous silica nano-particle sterling.
Fig. 1 is the TEM figures of prepared mesoporous silica nano-particle.It can be seen that its particle diameter is about 100 nm.
The mesoporous silica nano-particle of the surface amination of embodiment 2 modification（MSN-NH2）Preparation
Take obtained mesoporous silica nano-particle in 100 mg embodiments 1 to be dissolved in 20 mL absolute ethyl alcohols, add 400 μ g
3- aminopropyl triethoxysilanes, 12 h are stirred at room temperature, centrifuge, repeatedly washed with ethanol to remove unreacted 3- aminopropyls three
Ethoxysilane, freeze-drying obtain the mesoporous silica nano-particle of surface amino groups modification（MSN-NH2）.
Embodiment 3 loads Sorafenib mesoporous silica nano-particle（SO@MSN）Preparation
Take obtained MSN-NH in 30 mg embodiments 22It is dissolved in 30 mL acetone, Suo Lafei is added after stirring 1 h at room temperature
The mg of Buddhist nun 20, is stirred for 30min, and 30 min, abandoning supernatant, gained precipitation deionized water are then centrifuged under 13000rpm
Washing, freeze-drying, produce the mesoporous silica nano-particle for loading Sorafenib（SO@MSN）.
Embodiment 4 loads mesoporous silicon oxide-lactobionic acid nano particle of Sorafenib（SO@MSN-LA）Preparation
LA is activated first, i.e., 40 mg lactobionic acids, 100 mg dichloroethanes and the water of 0.1 mol mono- are added in reaction bulb
Quinoline ethyl sulfonic acid（MES, pH=6）, 24 h are stirred at room temperature, produce the LA of activation.
Take obtained SO@MSN in 30 mg embodiments 3,20 mL N,N-dimethylformamides, 100 mg 1- (3- diformazans
Aminopropyl) -3- ethyl-carbodiimide hydrochlorides（EDC）With 40 mg n-hydroxysuccinimides（NHS）In round-bottomed flask,
4 h are stirred at room temperature, and 2% mL of LA solution 5 is then added in mixed liquor, is stirred for 12 h, centrifuges, is washed with deionized
After be freeze-dried, produce load Sorafenib mesoporous silicon oxide-lactobionic acid nano particle（SO@MSN-LA）.
Fig. 2 is gained SO@MSN-LA grain size distribution.From Figure 2 it can be seen that its average grain diameter is about 150 nm.
Fig. 3 is mesoporous silicon oxide（MSN）, surface amination modification mesoporous silicon oxide（MSN-NH2）, activation breast
Uronic acid（LA）With mesoporous silicon oxide-lactobionic acid of load Sorafenib（SO@MSN-LA）Infrared absorpting light spectra.
Fig. 4 is mesoporous silicon oxide（MSN）, surface amination modification mesoporous silicon oxide（MSN-NH2）With load rope
La Feini mesoporous silicon oxide-lactobionic acid（SO@MSN-LA）Zeta electric potential figure.As seen from Figure 4, MSN average Zeta
Potential is about -19 mV, MSN-NH2Average Zeta electric potential be about+27 mV, i.e. MSN aminations after-potential is changed into just from negative value
Value, shows to be successfully prepared MSN-NH2；And SO@MSN-LA Zeta electric potential is+17 mv.
Embodiment 5 loads Sorafenib/siRNA mesoporous silicon oxide-lactobionic acid nano particle（SO/siRNA@
MSN-LA）Preparation
Weigh obtained SO@MSN-LA in 20 mg embodiments 4 to be dissolved in 20 mL acetone, the min of ultrasonic disperse 10, then therefrom
Take 6 μ L and 2 μ g siRNA to stir 20 min, produce load Sorafenib and siRNA mesoporous silicon oxide-lactobionic acid
Nano particle（SO/siRNA@MSN-LA）.
The measure of the Sorafenib vitro release of embodiment 6
SO@MSN prepared by Sorafenib, embodiment 3 and each 2 mg of SO@MSN-LA prepared by embodiment 4 are taken, is suspended in 2 respectively
In the PBS of mL pH=7.4, isothermal vibration carries out extracorporeal releasing experiment at 37 DEG C.500 μ L sample liquids are taken in different time,
After 10 min are centrifuged under 13000 rpm, the Sorafenib detected using ultraviolet specrophotometer under 210 nm in supernatant is dense
Degree, cumulative release percentage and the graph of a relation of time are drawn, as a result as shown in Figure 5.
As shown in Figure 5, SO@MSN and SO@MSN-LA Sorafenib release rate does not have significant difference, illustrates using breast
Uronic acid is the release that targeted molecular will not hinder Sorafenib.
The MTT experiment of embodiment 7
First, Huh7 cells and HepG2 cells are cultivated respectively, when its be in exponential phase and it is in good condition when, use tryptose
After enzymic digestion, blood counting chamber counts, and adjustment cell density is 1 × 105Individual/mL, is made into cell suspension；Connect by every μ L of hole 100
Kind, around with PBS shroudings, is placed in 37 DEG C, 5 % CO to 96 orifice plates2Culture overnight in incubator；When cytoactive reaches 80%
MSN-LA, SO@MSN, SO@MSN-LA, SO/siRNA the@MSN-LA and SO for the various concentrations gradient that addition is incubated with nutrient solution,
Cultivate 24 h；Nutrient solution is removed, adds the MTT solution after 100 μ L serum-frees dilute without phenol red medium, 37 DEG C of cultures 4
h；96 orifice plates are taken out, 100 μ L DMSO are added after suctioning out MTT solution, and 10 min are slowly rocked on shaking table, shake up rear more work(
Energy ELIASA detects OD values at 570 nm, cell proliferation inhibition rate is calculated using GraphPad Prism 5, as a result such as Fig. 6 institutes
Show.
As seen from Figure 6, MSN-LA does not almost have inhibitory action to Huh7 cells and HepG2 cells, and SO, SO@MSN, SO@
MSN-LA and SO/siRNA@MSN-LA are improved successively to the inhibiting rate of Huh7 cells and HepG2 cells, and are pressed down with the increase of dosage
Effect processed becomes apparent.Wherein, Carbazole alkaloid effects of the SO@MSN-LA to Huh7 cells and HepG2 cells（Cell is lived after processing
Property is respectively 12% and 18%）It is substantially better than SO@MSN（Cytoactive is respectively 28% and 30% after processing）, this explanation is by it
Upper coupling lactobionic acid molecule can improve the antitumous effect of Sorafenib；In addition, SO/siRNA@MSN-LA inhibition
（Cytoactive is 4% and 7% after processing）Notable compared with SO@MSN-LA, this explanation, compared with SO independent medications, SO is total to siRNA
The therapeutic effect of Synergistic can be played by loading on nanoparticle.
The Apoptosis assay of embodiment 8
Apoptosis assay is determined by flow cytometry.The inoculation of HepG2 cells is applied separately to addition and had in embodiment 2 prepare
MSN-NH2（Control）, SO@MSN that prepare of Sorafenib, embodiment 3, embodiment 4 prepare SO@MSN-LA, embodiment 5 makes
In standby SO/siRNA@MSN-LA 6 orifice plate nutrient solutions, adjustment cell density is 1 × 105Individual/orifice plate, cultivated at 37 DEG C
24 h, then centrifuged 5 minutes under 1500 rpm and obtain cell, washed three times with PBS, cell is suspended in 500 1 × combinations of μ L
It is 1 with Annexin-V FITC and PI volume ratios in buffer solution:1 10 μ L mixed liquors colour 10 min in the dark, finally
Obtained sample flow cytomery, as a result as shown in Figure 7.
Shown by Fig. 7 results, either early apoptosis or late apoptic, SO/siRNA@MSN-LA facilitation is all
Stronger than SO@MSN-LA, SO@MSN and independent application Sorafenib is more, illustrates that SO/siRNA@MSN-LA can be carried significantly
The anticancer effect of high Sorafenib and siRNA, that is, the effect of playing synergistic antitumor.
The cellular uptake of embodiment 9 is tested
2mg FITC and 20 μ L APTMS are added in 2 mL ethanol, and at room temperature lucifuge stirring 12h, make FITC first with
APTES covalent couplings；200 mg MSN and MSN-LA are dissolved in 50 mL ethanol and ultrasonic 30min respectively, then with 3mL
FITC/APTES ethanol solutions mix, and lucifuge stirring 24h, mixture are centrifuged and washs purifying with straight alcohol, that is, obtains FITC
MSN and FITC@MSN-LA nano particles.HepG2 cells are seeded in the μ L of nutrient solution containing DMEM 400 24 orifice plates, adjust cell
Density is 5 × 105Individual/orifice plate, 24 h are cultivated at 37 DEG C.After cell attachment grows, nutrient solution is discarded, culture plate is washed with PBS
Wash three times, then, be separately added into 100 μ g/mL FITC@MSN, FITC@MSN-LA and FITC@MSN-LA+LA in cell, 37
2 h are cultivated at DEG C.Cells rinsed with PBS in orifice plate is three times afterwards used nuclear targeting, final sample with Hoechst 33342
Laser Scanning Confocal Microscope is observed, as a result as shown in Figure 8.
As seen from Figure 8, FITC@MSN-LA fluorescence intensity is maximum, illustrates uptake ratio highest of the cell to it.And
FITC@MSN-LA+LA fluorescence intensity will be slightly less than FITC@MSN-LA, illustrate that LA can compete cancer cell with FITC@MSN-LA
On acceptor, further demonstrate LA target anticancer effect.
The in-vitro transfection of embodiment 10 is tested
2 μ g siRNA are separately added into 6 μ L MSN and 6 μ L MSN-LA, are slowly stirred 20 min at room temperature, you can obtain
SiRNA@MSN and siRNA@MSN-LA.HepG2 cells are inoculated into 24 orifice plates, adjustment cell density is 5 × 105Individual/hole
Plate, after cultivating 24 h, siRNA is separately added into nutrient solution and is made in advance siRNA@MSN and siRNA@MSN-LA, transfection
48 h.After transfection, cell is with Olympus IX71 fluorescence microscopies results and calculates transfection efficiency, as a result such as Fig. 9 institutes
Show.
As seen from Figure 9, free siRNA transfection efficiency is only 4.5%, less than siRNA@MSN（23%）, illustrate with nano particle
SiRNA stability can be improved for carrier, strengthens transfection efficiency；And siRNA@MSN-LA transfection efficiency is up to 45%, idol is indicated
Connection LA can play target anticancer effect.
The foregoing is only presently preferred embodiments of the present invention, all equivalent changes done according to scope of the present invention patent with
Modification, it should all belong to the covering scope of the present invention.
Claims (7)
1. one kind load Sorafenib/siRNA mesoporous silicon oxide-lactobionic acid targeted nano particle, it is characterised in that：Its
Preparation method comprises the following steps：
1）Amination modification is carried out to mesoporous silica nano-particle surface；
2）The inner duct for the mesoporous silicon oxide that Sorafenib is loaded to after amination modification；
3）Lactobionic acid is coupled to the outer surface for the mesoporous silicon oxide for being loaded with Sorafenib by covalent bond；
4）SiRNA is adsorbed onto by step 3 by electrostatic adsorption）Gained mesoporous silicon oxide-lactobionic acid coupled product
Outer surface.
2. Sorafenib/siRNA mesoporous silicon oxide-lactobionic acid targeted nano particle is loaded according to claim 1,
It is characterized in that：Step 1）In the particle diameter of mesoporous silica nano-particle used be 100nm.
3. Sorafenib/siRNA mesoporous silicon oxide-lactobionic acid targeted nano particle is loaded according to claim 1,
It is characterized in that：Step 1）Concrete operations be：Mesoporous silica nano-particle is dissolved in absolute ethyl alcohol, adds nanometer
The 3- aminopropyl triethoxysilanes of grain weight 0.4%, are centrifuged after 12h is stirred at room temperature, ethanol washing, freeze-drying.
4. Sorafenib/siRNA mesoporous silicon oxide-lactobionic acid targeted nano is loaded according to claim 1
Grain, it is characterised in that：Step 2）Concrete operations be：Mesoporous silicon oxide after amination is modified dissolves in acetone, room
Sorafenib is added after 1 h of the lower stirring of temperature, is stirred for 30min, 30 min are then centrifuged under 13000rpm, gained precipitation is spent
Ion water washing, freeze-drying；
Wherein, the weight ratio of the mesoporous silicon oxide after amination modification and Sorafenib is 3:2.
5. Sorafenib/siRNA mesoporous silicon oxide-lactobionic acid targeted nano particle is loaded according to claim 1,
It is characterized in that：Step 3）Concrete operations be：Using DMF as solvent, Jie for being loaded with Sorafenib is added
Hole silica, EDC and NHS, after stirring 4h at room temperature, by volume 4:1 adds the lactobionic acid solution that mass concentration is 2%,
Continue to stir 12h, be then centrifuged for, be freeze-dried after deionized water is washed；
Wherein, the weight ratio for being loaded with the mesoporous silicon oxide of Sorafenib, EDC and NHS is 3:10:4；
The lactobionic acid solution is to stir 40 mg lactobionic acids, 100 mg dichloroethanes and 0.1 mol MES at room temperature
24 h are made.
6. Sorafenib/siRNA mesoporous silicon oxide-lactobionic acid targeted nano is loaded according to claim 1
Grain, it is characterised in that：Step 4）Concrete operations be：Mesoporous silicon oxide-lactobionic acid coupled product is added in acetone, surpassed
Sound disperses 10min, then by mass volume ratio 1:3 g/L add siRNA in the solution, stir 20min.
A kind of 7. application of the targeted nano particle on cancer therapy drug is prepared as claimed in claim 1.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710562955.XA CN107349432B (en) | 2017-07-11 | 2017-07-11 | Sorafenib/siRNA-loaded mesoporous silica-lactobionic acid targeted nanoparticles |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710562955.XA CN107349432B (en) | 2017-07-11 | 2017-07-11 | Sorafenib/siRNA-loaded mesoporous silica-lactobionic acid targeted nanoparticles |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN107349432A true CN107349432A (en) | 2017-11-17 |
| CN107349432B CN107349432B (en) | 2020-05-08 |
Family
ID=60291953
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201710562955.XA Expired - Fee Related CN107349432B (en) | 2017-07-11 | 2017-07-11 | Sorafenib/siRNA-loaded mesoporous silica-lactobionic acid targeted nanoparticles |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN107349432B (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108904811A (en) * | 2018-07-17 | 2018-11-30 | 福州大学 | It is a kind of based on aptamers modification hollow mesoporous silicon oxide be total to charge material grain multifunctional nano drug preparation and its application |
| CN112624967A (en) * | 2019-10-08 | 2021-04-09 | 复旦大学 | Sorafenib mercapto derivative and application thereof |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104225599A (en) * | 2013-06-14 | 2014-12-24 | 吉林大学 | Asymmetric magnetic mesoporous silica rod supporting chemotherapeutic and gene drugs and application thereof to tumor diagnosis and treatment |
| CN105343895A (en) * | 2015-12-04 | 2016-02-24 | 福州大学 | Dual-targeting ursolic acid (UA)/siRNA loaded fluorescent mesoporous silica dioxide-hyaluronic acid and application |
| WO2016149378A1 (en) * | 2015-03-16 | 2016-09-22 | Pdx Pharmaceuticals, Llc | Cross-linked polymer modified nanoparticles |
-
2017
- 2017-07-11 CN CN201710562955.XA patent/CN107349432B/en not_active Expired - Fee Related
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104225599A (en) * | 2013-06-14 | 2014-12-24 | 吉林大学 | Asymmetric magnetic mesoporous silica rod supporting chemotherapeutic and gene drugs and application thereof to tumor diagnosis and treatment |
| WO2016149378A1 (en) * | 2015-03-16 | 2016-09-22 | Pdx Pharmaceuticals, Llc | Cross-linked polymer modified nanoparticles |
| CN105343895A (en) * | 2015-12-04 | 2016-02-24 | 福州大学 | Dual-targeting ursolic acid (UA)/siRNA loaded fluorescent mesoporous silica dioxide-hyaluronic acid and application |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108904811A (en) * | 2018-07-17 | 2018-11-30 | 福州大学 | It is a kind of based on aptamers modification hollow mesoporous silicon oxide be total to charge material grain multifunctional nano drug preparation and its application |
| CN108904811B (en) * | 2018-07-17 | 2021-07-13 | 福州大学 | Preparation and application of aptamer-modified silicon dioxide nano-drug |
| CN112624967A (en) * | 2019-10-08 | 2021-04-09 | 复旦大学 | Sorafenib mercapto derivative and application thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| CN107349432B (en) | 2020-05-08 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Knežević et al. | Targeted treatment of cancer with nanotherapeutics based on mesoporous silica nanoparticles | |
| CN105343895B (en) | A kind of load ursolic acid/siRNA fluorescence mesoporous silicon oxide-hyaluronic acid of dual-target and application | |
| CN107753946A (en) | A kind of targeted medicament carrying nano grain of aptamers modification and preparation method and application | |
| CN113289030B (en) | Preparation method of targeting long-circulating nano-drug carrier for photo-thermal synergistic chemotherapy | |
| CN103784407B (en) | Graphene oxide-loaded adriamycin nano-particles of a kind of folate-mediated PEG-and preparation method thereof | |
| Jin et al. | Nanoscale dual-enzyme cascade metal–organic frameworks through biomimetic mineralization as ROS generators for synergistic cancer therapy | |
| Sayed et al. | Silica nanoparticles sensitize human multiple myeloma cells to snake (Walterinnesia aegyptia) venom‐induced apoptosis and growth arrest | |
| CN104840966B (en) | A kind of nucleic acid nano structure anticancer combination drug and its preparation method and application | |
| CN101768276B (en) | Methoxy polyethylene glycol-polycaprolactone-polyethyleneimine triblock copolymer and application thereof | |
| CN112294751B (en) | Preparation method and application of calcium peroxide-loaded metal-organic framework pharmaceutical composition | |
| CN106929508B (en) | SaRNA for activating PTPRO gene expression and transport vector thereof | |
| CN105997881A (en) | Tumor cell targeting mesoporous silicon nanometer assembly and preparation method for same | |
| CN107349432A (en) | One kind load Sorafenib/siRNA mesoporous silicon oxide lactobionic acid targeted nano particle | |
| Kang et al. | Flexible human serum albumin nanocapsules to enhance drug delivery and cellular uptake for photodynamic/chemo cancer therapy | |
| Parnian et al. | Overcoming the non-kinetic activity of EGFR1 using multi-functionalized mesoporous silica nanocarrier for in vitro delivery of siRNA | |
| CN106729746A (en) | To FAP α enzymes, the preparation method and applications of the tumor infiltrating nanosystems of the particle diameter shrinkage type of reducing environment sensitive | |
| CN107007550B (en) | Redox-responsive amphiphilic copolymer and preparation method and application thereof | |
| Fadaka et al. | Stage-specific treatment of colorectal cancer: A microRNA-nanocomposite approach | |
| CN109224063A (en) | The nano combined carrier and its preparation and application of dual load peptides and chemotherapeutics | |
| CN102512683A (en) | Polymer gene medicine carrier, preparation method thereof and use thereof for preparing antitumor medicine | |
| CN104027821A (en) | siRNA-loading nanoparticle and application thereof | |
| Zeng et al. | Biodegradable nano-organosilica gene carrier for high-efficiency gene transfection | |
| Hao et al. | Manganese doped nanosystem for degrading neutrophil extracellular traps and improving chemotherapy efficiency to synergistically inhibit lung metastasis of breast cancer | |
| CN107970242B (en) | Paclitaxel/erlotinib loaded mesoporous silica-hyaluronic acid mixed targeting nanoparticles | |
| CN110917172B (en) | Molybdenum oxide nanosheet plugging hollow mesoporous silicon nanomaterial and preparation and application thereof |
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 | ||
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20200508 |