CN106913884A - A kind of nano-complex of polynucleotide and gold nanorods and its production and use - Google Patents
A kind of nano-complex of polynucleotide and gold nanorods and its production and use Download PDFInfo
- Publication number
- CN106913884A CN106913884A CN201710281508.7A CN201710281508A CN106913884A CN 106913884 A CN106913884 A CN 106913884A CN 201710281508 A CN201710281508 A CN 201710281508A CN 106913884 A CN106913884 A CN 106913884A
- Authority
- CN
- China
- Prior art keywords
- gold nanorods
- polynucleotide
- gnrs
- complex
- nano
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 title claims abstract description 50
- 108091033319 polynucleotide Proteins 0.000 title claims abstract description 36
- 239000002157 polynucleotide Substances 0.000 title claims abstract description 36
- 102000040430 polynucleotide Human genes 0.000 title claims abstract description 36
- 206010028980 Neoplasm Diseases 0.000 claims abstract description 24
- 150000001875 compounds Chemical class 0.000 claims abstract description 22
- 238000012986 modification Methods 0.000 claims abstract description 22
- 230000004048 modification Effects 0.000 claims abstract description 22
- 238000011282 treatment Methods 0.000 claims abstract description 21
- 235000019136 lipoic acid Nutrition 0.000 claims abstract description 20
- 229960002663 thioctic acid Drugs 0.000 claims abstract description 19
- 230000002195 synergetic effect Effects 0.000 claims abstract description 13
- 229910052751 metal Inorganic materials 0.000 claims abstract description 11
- 239000002184 metal Substances 0.000 claims abstract description 11
- 239000003446 ligand Substances 0.000 claims abstract description 7
- 201000011510 cancer Diseases 0.000 claims abstract description 5
- AGBQKNBQESQNJD-UHFFFAOYSA-M lipoate Chemical compound [O-]C(=O)CCCCC1CCSS1 AGBQKNBQESQNJD-UHFFFAOYSA-M 0.000 claims abstract 7
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 14
- 238000006243 chemical reaction Methods 0.000 claims description 13
- 238000002360 preparation method Methods 0.000 claims description 12
- OISVCGZHLKNMSJ-UHFFFAOYSA-N 2,6-dimethylpyridine Chemical class CC1=CC=CC(C)=N1 OISVCGZHLKNMSJ-UHFFFAOYSA-N 0.000 claims description 11
- ONDPHDOFVYQSGI-UHFFFAOYSA-N zinc nitrate Chemical compound [Zn+2].[O-][N+]([O-])=O.[O-][N+]([O-])=O ONDPHDOFVYQSGI-UHFFFAOYSA-N 0.000 claims description 6
- 239000000084 colloidal system Substances 0.000 claims description 5
- 230000000536 complexating effect Effects 0.000 claims description 5
- 238000005516 engineering process Methods 0.000 claims description 5
- 239000000203 mixture Substances 0.000 claims description 5
- 239000002994 raw material Substances 0.000 claims description 4
- 238000003786 synthesis reaction Methods 0.000 claims description 4
- LZZYPRNAOMGNLH-UHFFFAOYSA-M Cetrimonium bromide Chemical compound [Br-].CCCCCCCCCCCCCCCC[N+](C)(C)C LZZYPRNAOMGNLH-UHFFFAOYSA-M 0.000 claims description 3
- 230000015572 biosynthetic process Effects 0.000 claims description 3
- 239000012153 distilled water Substances 0.000 claims description 3
- 239000000126 substance Substances 0.000 claims description 3
- 229910021642 ultra pure water Inorganic materials 0.000 claims description 3
- 239000012498 ultrapure water Substances 0.000 claims description 3
- 150000002739 metals Chemical class 0.000 claims description 2
- 108091070501 miRNA Proteins 0.000 claims description 2
- 239000002679 microRNA Substances 0.000 claims description 2
- 150000003222 pyridines Chemical class 0.000 claims description 2
- 238000009472 formulation Methods 0.000 claims 1
- 108090000623 proteins and genes Proteins 0.000 abstract description 19
- 230000000694 effects Effects 0.000 abstract description 10
- 230000001225 therapeutic effect Effects 0.000 abstract description 7
- 230000030279 gene silencing Effects 0.000 abstract description 6
- 238000012226 gene silencing method Methods 0.000 abstract description 6
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 abstract description 4
- PTFCDOFLOPIGGS-UHFFFAOYSA-N Zinc dication Chemical compound [Zn+2] PTFCDOFLOPIGGS-UHFFFAOYSA-N 0.000 abstract description 4
- 238000002474 experimental method Methods 0.000 abstract description 4
- 238000000338 in vitro Methods 0.000 abstract description 4
- 238000001727 in vivo Methods 0.000 abstract description 3
- 229910000147 aluminium phosphate Inorganic materials 0.000 abstract description 2
- 210000005170 neoplastic cell Anatomy 0.000 abstract description 2
- PXFBZOLANLWPMH-UHFFFAOYSA-N 16-Epiaffinine Natural products C1C(C2=CC=CC=C2N2)=C2C(=O)CC2C(=CC)CN(C)C1C2CO PXFBZOLANLWPMH-UHFFFAOYSA-N 0.000 abstract 1
- 108020004459 Small interfering RNA Proteins 0.000 description 67
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 21
- 210000004027 cell Anatomy 0.000 description 19
- 239000000243 solution Substances 0.000 description 14
- -1 anion lipid Chemical class 0.000 description 12
- AGBQKNBQESQNJD-UHFFFAOYSA-N lipoic acid Chemical compound OC(=O)CCCCC1CCSS1 AGBQKNBQESQNJD-UHFFFAOYSA-N 0.000 description 10
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 8
- 238000005292 vacuum distillation Methods 0.000 description 7
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
- 238000003384 imaging method Methods 0.000 description 6
- 235000002639 sodium chloride Nutrition 0.000 description 6
- 238000003756 stirring Methods 0.000 description 6
- 230000008859 change Effects 0.000 description 5
- 238000001914 filtration Methods 0.000 description 5
- 239000012266 salt solution Substances 0.000 description 5
- 239000013598 vector Substances 0.000 description 5
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
- 238000001035 drying Methods 0.000 description 4
- 239000000499 gel Substances 0.000 description 4
- 239000010410 layer Substances 0.000 description 4
- 238000007626 photothermal therapy Methods 0.000 description 4
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
- 229920006395 saturated elastomer Polymers 0.000 description 4
- 239000011780 sodium chloride Substances 0.000 description 4
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 4
- 210000004881 tumor cell Anatomy 0.000 description 4
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- 241000699666 Mus <mouse, genus> Species 0.000 description 3
- 241000699670 Mus sp. Species 0.000 description 3
- 206010060862 Prostate cancer Diseases 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 239000002253 acid Substances 0.000 description 3
- 150000001412 amines Chemical class 0.000 description 3
- 230000000692 anti-sense effect Effects 0.000 description 3
- 150000001768 cations Chemical class 0.000 description 3
- 230000009368 gene silencing by RNA Effects 0.000 description 3
- 238000011534 incubation Methods 0.000 description 3
- 238000000034 method Methods 0.000 description 3
- 239000012074 organic phase Substances 0.000 description 3
- 239000007787 solid Substances 0.000 description 3
- 230000001629 suppression Effects 0.000 description 3
- 239000011701 zinc Substances 0.000 description 3
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- 229910019142 PO4 Inorganic materials 0.000 description 2
- 238000012228 RNA interference-mediated gene silencing Methods 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 2
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 2
- 150000001450 anions Chemical class 0.000 description 2
- 230000000259 anti-tumor effect Effects 0.000 description 2
- 238000003556 assay Methods 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 229940125782 compound 2 Drugs 0.000 description 2
- 229940126214 compound 3 Drugs 0.000 description 2
- 239000012043 crude product Substances 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 238000001962 electrophoresis Methods 0.000 description 2
- 230000014509 gene expression Effects 0.000 description 2
- 238000001415 gene therapy Methods 0.000 description 2
- 239000001963 growth medium Substances 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 239000013642 negative control Substances 0.000 description 2
- 238000011580 nude mouse model Methods 0.000 description 2
- 239000010452 phosphate Substances 0.000 description 2
- 229910000027 potassium carbonate Inorganic materials 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 150000003839 salts Chemical class 0.000 description 2
- HJUGFYREWKUQJT-UHFFFAOYSA-N tetrabromomethane Chemical compound BrC(Br)(Br)Br HJUGFYREWKUQJT-UHFFFAOYSA-N 0.000 description 2
- 231100000419 toxicity Toxicity 0.000 description 2
- 230000001988 toxicity Effects 0.000 description 2
- 230000004614 tumor growth Effects 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- 229910052725 zinc Inorganic materials 0.000 description 2
- LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide Substances CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 1
- ICSNLGPSRYBMBD-UHFFFAOYSA-N 2-aminopyridine Chemical compound NC1=CC=CC=N1 ICSNLGPSRYBMBD-UHFFFAOYSA-N 0.000 description 1
- SDXAWLJRERMRKF-UHFFFAOYSA-N 3,5-dimethyl-1h-pyrazole Chemical compound CC=1C=C(C)NN=1 SDXAWLJRERMRKF-UHFFFAOYSA-N 0.000 description 1
- FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 1
- 229920001817 Agar Polymers 0.000 description 1
- 229920000936 Agarose Polymers 0.000 description 1
- 108020004414 DNA Proteins 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000331 Firefly luciferases Proteins 0.000 description 1
- PWKSKIMOESPYIA-BYPYZUCNSA-N L-N-acetyl-Cysteine Chemical compound CC(=O)N[C@@H](CS)C(O)=O PWKSKIMOESPYIA-BYPYZUCNSA-N 0.000 description 1
- 241000254158 Lampyridae Species 0.000 description 1
- 229910010084 LiAlH4 Inorganic materials 0.000 description 1
- 108060001084 Luciferase Proteins 0.000 description 1
- 239000005089 Luciferase Substances 0.000 description 1
- 241000699660 Mus musculus Species 0.000 description 1
- 240000007594 Oryza sativa Species 0.000 description 1
- 235000007164 Oryza sativa Nutrition 0.000 description 1
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 1
- 208000000236 Prostatic Neoplasms Diseases 0.000 description 1
- 108700008625 Reporter Genes Proteins 0.000 description 1
- 235000010724 Wisteria floribunda Nutrition 0.000 description 1
- 241000021375 Xenogenes Species 0.000 description 1
- 239000008272 agar Substances 0.000 description 1
- 238000000246 agarose gel electrophoresis Methods 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 210000001367 artery Anatomy 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 239000012620 biological material Substances 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 239000007853 buffer solution Substances 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 229920006317 cationic polymer Polymers 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 230000004700 cellular uptake Effects 0.000 description 1
- 239000002131 composite material Substances 0.000 description 1
- 229940125904 compound 1 Drugs 0.000 description 1
- 229940125898 compound 5 Drugs 0.000 description 1
- 210000000805 cytoplasm Anatomy 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 238000007599 discharging Methods 0.000 description 1
- 238000002296 dynamic light scattering Methods 0.000 description 1
- ZMMJGEGLRURXTF-UHFFFAOYSA-N ethidium bromide Chemical compound [Br-].C12=CC(N)=CC=C2C2=CC=C(N)C=C2[N+](CC)=C1C1=CC=CC=C1 ZMMJGEGLRURXTF-UHFFFAOYSA-N 0.000 description 1
- 229960005542 ethidium bromide Drugs 0.000 description 1
- XYIBRDXRRQCHLP-UHFFFAOYSA-N ethyl acetoacetate Chemical compound CCOC(=O)CC(C)=O XYIBRDXRRQCHLP-UHFFFAOYSA-N 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 238000001476 gene delivery Methods 0.000 description 1
- 230000037440 gene silencing effect Effects 0.000 description 1
- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- 238000009533 lab test Methods 0.000 description 1
- 239000012280 lithium aluminium hydride Substances 0.000 description 1
- 231100000053 low toxicity Toxicity 0.000 description 1
- 210000003712 lysosome Anatomy 0.000 description 1
- 230000001868 lysosomic effect Effects 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 239000002609 medium Substances 0.000 description 1
- XDMFYOPNYBTJLJ-UHFFFAOYSA-N n-bromobutan-1-amine Chemical compound CCCCNBr XDMFYOPNYBTJLJ-UHFFFAOYSA-N 0.000 description 1
- 239000002539 nanocarrier Substances 0.000 description 1
- 239000002086 nanomaterial Substances 0.000 description 1
- 239000002105 nanoparticle Substances 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 239000002777 nucleoside Substances 0.000 description 1
- 150000003833 nucleoside derivatives Chemical class 0.000 description 1
- 238000005457 optimization Methods 0.000 description 1
- 239000012044 organic layer Substances 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 125000002467 phosphate group Chemical group [H]OP(=O)(O[H])O[*] 0.000 description 1
- 150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- 239000011574 phosphorus Substances 0.000 description 1
- 150000003022 phthalic acids Chemical class 0.000 description 1
- 239000002504 physiological saline solution Substances 0.000 description 1
- 239000013641 positive control Substances 0.000 description 1
- 235000009566 rice Nutrition 0.000 description 1
- 238000010898 silica gel chromatography Methods 0.000 description 1
- 239000001488 sodium phosphate Substances 0.000 description 1
- 229910000162 sodium phosphate Inorganic materials 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-N sulfuric acid Substances OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 230000009182 swimming Effects 0.000 description 1
- 230000008685 targeting Effects 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 238000013518 transcription Methods 0.000 description 1
- 230000035897 transcription Effects 0.000 description 1
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 1
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 1
- 210000003462 vein Anatomy 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
- A61K41/0052—Thermotherapy; Hyperthermia; Magnetic induction; Induction heating therapy
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K49/00—Preparations for testing in vivo
- A61K49/22—Echographic preparations; Ultrasound imaging preparations ; Optoacoustic imaging preparations
- A61K49/221—Echographic preparations; Ultrasound imaging preparations ; Optoacoustic imaging preparations characterised by the targeting agent or modifying agent linked to the acoustically-active agent
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Epidemiology (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical & Material Sciences (AREA)
- Molecular Biology (AREA)
- Physics & Mathematics (AREA)
- Acoustics & Sound (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Radiology & Medical Imaging (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Abstract
Nano-complex the invention discloses a kind of polynucleotide and gold nanorods and its production and use.In the present invention, gold nanorods surface is modified using the polynucleotide carrier compound that a kind of lipoic acid that can be highly affine with phosphoric acid molecules is modified.The polynucleotide carrier compound can be used as the effective carrier of therapeutic gene with the gold nanorods of zinc ion metal organic complexes modification.In the present invention, due to surface modification gold nanorods and therapeutic gene strong ligand complex act on cause nano-complex there is high stability, in vivo with experiment in vitro in, all therapeutic gene efficiently can be delivered into targets neoplastic cells.Gene/photo-thermal the Synergistic treatment to cancer is reached using gene silencing and gold nanorods light thermal activities.
Description
Technical field
The present invention relates to a kind of gold nanorods based on surface modification are as genophore and to be applied to cancer efficient
Gene-photo-thermal Synergistic treatment, belongs to biological medicine material and nanosecond medical science field.
Background technology
RNA interference (RNAi) is to cause gene silencing after transcription using specific gene sequences, in treatment of cancer side
There are very big potentiality in face.But, although siRNA (siRNA) technology has become a kind of effective therapeutic scheme, but by
It is larger in siRNA phosphate backbones anionic charge and molecular weight, cause the delivering of siRNA to be limited, obtained after being administered systemically
Poor pharmacokinetics and relatively low intracellular rate.So, so far clinically still without being successfully used to oncotherapy
SiRNA preparations.Although being much based on cationic polymer, the siRNA delivery vectors of anion lipid or amino acid can be effective
Carrying anion RNAis reach effect to oncotherapy, but the serious toxic and side effect of these strong cation carriers is limited
Its vivo applications.In order to overcome these obstacles, efficient siRNA delivery vectors pair how are researched and developed without strong cation derivative
It is still a challenge for researcher.
Due to there is specific interaction between lutidines amine metal organic complexes and the anion of phosphate group,
So that its molecule (such as therapeutic gene) to phosphoric acid has high-affinity, so many lutidines amine metal organic composites
Thing is used for the biological important phosphoric acid derivatives of detection.The nanometer system of lutidines amine metal organic complexes and tradition
Gene delivery vector compare, cation is significantly reduced, therefore, it is serving as nontoxic and efficient treatment diagnostic gene carrier side
, there is very big development potentiality in face.However, application of the lutidines amine metal organic complexes in siRNA deliverings field needs
Further investigation, especially Gene releaser behavior aspect efficiency need further optimization and improve.
It is attractive delivering siRNA that one layer of organic or bio-molecule layer multi-functional gold nanorods are wrapped up on surface
Nano-carrier.Due to its adjustable size, monodispersity, low toxicity, unique size, adjustable function of surface and optoacoustic are disconnected
The ability of layer scanning, these nano materials have very big prospect in terms of medicine delivery.Due to the strong plasma resonance of gold nanorods
Peak, when near infrared light and plasma resonance are Wavelength matched, gold nanorods can be collided by Electron-phonon effectively will
Luminous energy changes into surface part heat energy, namely photothermal conversion.Heat passes to the cellular environment of surrounding from gold nanorods surface, is received several
Exponentially decay in the distance of rice, therefore the damage effect to normal cell can be reduced.So, to targets neoplastic cells or group
Knit when carrying out photo-thermal therapy, these characteristics can reduce the damage to healthy cell, while can also combine with therapeutic gene being assisted
With treatment, antitumous effect is enhanced.
The content of the invention
Primary and foremost purpose of the invention is the nano-complex for providing a kind of polynucleotide and gold nanorods；
Another object of the present invention is to provide a kind of polynucleotide carrier compound work(of surface lipoic acid modification
The preparation method of the gold nanorods of energyization；
It is that the nano-complex of polynucleotide and gold nanorods is applied to the base of cancer that another object of the present invention is
The method of cause-photo-thermal Synergistic treatment.
The purpose of the present invention can be achieved through the following technical solutions：
A kind of nano-complex of polynucleotide and gold nanorods, it is characterized by nano-complex include gold nanorods,
Polynucleotide and their organic molecule of connection.
Wherein, in gold nanorods of the described gold nanorods including common gold nanorods or other metals that adulterate
Kind, the present invention have selected common gold nanorods.
Wherein, described organic molecule is the polynucleotide carrier compound of lipoic acid modification.
Wherein, described polynucleotide is ODN, and at least one in DNA, miRNA or siRNA is excellent in the present invention
Select siRNA.
The nano-complex preparation method of polynucleotide and gold nanorods in the present invention, comprises the following steps：
1) lipoic acid modification, can be combined siRNA carrier preparation.With 5- Hydroxy M Phthalic Acids, lutidines amine,
, without raw material, by multistep organic synthesis means, having synthesized can be with the chemical combination of gold nanorods ligand exchange for (±)-alpha-lipoic acid etc.
Thing.
2) gold nanorods of surface modification CTAB and the polymerized nucleoside acid vectors of lipoic acid modification pass through ligand exchange reaction,
The amine-modified gold nanorods of lutidines (ZD-GNRs) is synthesized.The lutidines amine that 2mL lipoic acids are modified is (molten
In ethanol) it is added slowly in the GNRs colloids of 10mL (gold nanorods colloid, 2nM), 12h is stirred at room temperature, the diformazan for obtaining
Yl pyridines amine-GNR solution is centrifuged three times under the rotating speed of 6000rpm, each 15min, is modified with removing unreacted lipoic acid
DPA.Afterwards, ZD-GNRs is distributed in the distilled water of 2mL.
3) siRNA/ZD-GNRs is prepared by metal organic complex technology.First, by zinc nitrate (5mL, 3mg/mL,
10.1mM) mix (5mL, 2mg/mL) with lutidines amine-GNRs, mixture is stirred at room temperature 30min.Then, 3 are centrifuged
Secondary (rotating speed is 5000rpm), to remove unreacted raw material, the ZD-GNR that will be obtained afterwards is distributed in ultra-pure water.By 2uL
ZD-GNR solution is well mixed with 1uL siRNA (FFL siRNA (siLuc) or PLK1siRNA (siPLK)),
Room temperature 30min is placed in, siRNA/ZD-GNRs is collected, in vitro and in vivo experiment.
Beneficial effects of the present invention：
1. in the nano-complex of siRNA of the present invention and gold nanorods, siRNA illustrates preferable active for gene silencing,
Gold nanorods illustrate preferable light thermal activities.
2. the strong ligand complex of the gold nanorods of surface modification and siRNA is acted on and causes that nano-complex has in the present invention
High stability.
3. carrying out gene/photo-thermal Synergistic treatment to tumour in the present invention will than single gene therapy and photo-thermal therapy effect
It is superior a lot.
4., due to the light acoustic performance of GNRs in the present invention, siRNA/ZD-GNRs can turn into carries out optoacoustic simultaneously to tumour
Imaging and the treatment diagnostic reagent for the treatment of.
Brief description of the drawings
The preparation flow of the polynucleotide carrier compound of Fig. 1 lipoic acids modification.
The sign of Fig. 2 siRNA/ZD-GNRs.Upper row is respectively the TEM of GNRs, ZD-GNRs and siRNA/GNRs.Lower row
For the electrophoresis retardation assays that siRNA and ZD-GNRs is combined：(swimming lane 1-5：SiRNA/ZD-GNRs mol ratios are 600,300,200,
100,50 complexing).
143B-fLuc tumour cell firefly fluorescence after Fig. 3 siLuc/LipoMax or siLuc/ZD-GNRs incubation
The bioluminescent assay of the suppression of plain enzyme (fLuc) gene expression.
Outer-gene/photo-thermal Synergistic treatments of Fig. 4 siRNA/ZD-GNRs to PC-3 cell lines.Whetheing there is 0.5W/ respectively
cm2Under the 808nm laser irradiation of power, 1 day (a) and the 2 days physiological saline of (b) incubated in vitro, ZD-GNRs and siPLK/ZD-
Toxicity of the GNRs to prostate gland cancer cell
Gene/photo-thermal Synergistic treatments of Fig. 5 SiRNA/ZD-GNRs to PC-3 tumor-bearing mices.With salt solution, ZD-GNRs and
After siRNA/ZD-GNRs processes tumor-bearing mice, and laser irradiation 10min, the temperature change of its infrared image (a) and tumor region
(b).Tumor volume change under (c) different treatments.D () processes the representative picture of 23 days PC-3 tumor-bearing mices afterwards.
Specific embodiment
Can be illustrated more clearly that the present invention below by way of specific preparation example and embodiment：
First, preparation example
1) synthesis of the polynucleotide carrier compound of lipoic acid modification
At room temperature, the concentrated sulfuric acid (1.0mL) of catalytic amount is added dropwise to the ethanol of compound 1 (18.2g, 0.1mol)
In (100mL) solution, stirring reaction is then refluxed for overnight.Room temperature is cooled to, vacuum distillation is evaporated, obtains 21.2 g of compound 2, received
Rate：89%.
Nitrogen is protected, under ice salt bath, anhydrous tetrahydro furan (80mL) solution of compound 2 (21.2g, 0.089mol) is slow
Slowly it is added dropwise to LiAlH4In anhydrous tetrahydro furan (50mL) suspension of (10.1g, 0.267mol), temperature maintains 0 DEG C or so.
After dripping, 0 DEG C of stirring reaction is maintained 30 minutes, be then return to room temperature, stirring reaction 5 hours.Cooled down under ice salt bath, slowly
Frozen water (100mL) is added dropwise, temperature maintains less than 0 DEG C, the hydrochloric acid of 1N is then slowly added dropwise again to pH value to 3, filtering, solid is used
Tetrahydrofuran (20mL*3) is washed, vacuum distillation filtrate, removes tetrahydrofuran, and water layer is extracted with dichloromethane (100mL*3), is received
Collection organic layer, washs, anhydrous sodium sulfate drying through saturated aqueous common salt (100mL), and filtering, vacuum distillation obtains 11.7 g of compound 3,
Yield：85%.
At room temperature, the bromo- 1- butylamine (23.0g, 0.091mol) of N-Boc-4- and potassium carbonate (21.0g, 0.152mol) are added
Enter in acetonitrile (110mL) solution of compound 3 (11.7g, 0.076mol), be refluxed overnight, vacuum distillation is done, and adds water
(50mL), then with the salt acid for adjusting pH value of 1N to 6, dichloromethane (100mL*3) is extracted, organic phase saturated aqueous common salt
(100mL*2) is washed, anhydrous sodium sulfate drying, and filtering, vacuum distillation obtains 26.4 g of compound 4, yield：89%.
At room temperature, carbon tetrabromide (64.5g, 0.194mol) and triphenyl phosphorus (42.5g, 0.162mol) are added into compound
In dichloromethane (300mL) solution of 4 (26.4g, 0.081mol), reaction is stirred at room temperature overnight.Then, 1N NaOH is used
(300mL) is quenched reaction.Point liquid, mutually with dichloromethane (200mL*2) extraction, organic phase is with saturated aqueous common salt (300mL*2) for water
Washing, anhydrous sodium sulfate drying, filtering, concentration is evaporated, and crude product is through silica gel column chromatography (ethyl acetate：Petroleum ether=3：1) separate
Obtain 26.3 g of compound 5, yield：72%.
At room temperature, lutidines amine (25.6g, 0.128mol) and potassium carbonate (24.0g, 0.174mol) are added into chemical combination
In DMF (100mL) solution of thing 5 (26.3g, 0.058mol), at 60 DEG C, stirring reaction 5 hours, vacuum distillation obtains crude product, first
After being washed with frozen water (200mL) and ether (200mL) afterwards, 33.1 g of compound 6, yield are vacuum dried to obtain：83%.
Under ice bath, trifluoroacetic acid (50mL) is added dropwise to the dichloromethane (50mL) of compound 6 (33.1g, 0.048mol)
In solution, after dripping, reaction is stirred at room temperature overnight, vacuum distillation, ether (100*3) washing is dry to take off Boc solids.
Under ice bath, by EDCI (12.0g, 0.063mol), HOBt (9.7g, 0.072mol) and triethylamine (9.7g,
0.096mol) in dichloromethane (100mL) solution of addition (±)-alpha-lipoic acid (9.9g, 0.048mol), after adding, room temperature
Stirring reaction 30 minutes, then by de- Boc solids addition solution above, stirring reaction overnight, adds saturated sodium bicarbonate
(100mL), point liquid, water is mutually extracted with dichloromethane (100mL*3), and organic phase merges, successively with saturated sodium bicarbonate (100mL*
3), 1N hydrochloric acid (100mL*3) and saturated aqueous common salt (100mL*2) are washed, and anhydrous sodium sulfate drying, filtering, evaporated under reduced pressure uses second
Acetoacetic ester recrystallizes to obtain 29.8 g of compound 7 (can be with the compound of gold nanorods ligand exchange), yield：80%.
2) in the present invention, firefly luciferase s
The sequence of siRNA (siLuc) be 5 '-GCACUCUGAUUGACAAA-UACGAUUU-3 ' (positive-sense strand) and 5 '-
AAAUCGUAUUUGUCAAUCAGAGUGC-3 ' (antisense strand), siRNA (siNC) sequence of negative control for 5 '-
AAUUCUCCGAACGUGUCACGU-3 ' (positive-sense strand) and 5 '-ACGUGACACGUUCGGAGAAUU-3 ' (antisense strand), and targeting
SiRNA (siPLK) sequence of PLK1mRNA be 5 '-UGAAGAA GAUCACCCUCCUUAdTdT-3 ' (positive-sense strand) and 5 '-
UAAGGAGGGU GAUCUfUCUfUCfAdTdT-3 ' (antisense strand).
3) as shown in figure 1, the polynucleotide carrier compound of synthesis lipoic acid modification.As shown in Figure 2 a, surface modification
The polynucleotide carrier compound of gold nanorods and the lipoic acid modification of cetyl trimethylammonium bromide passes through ligand exchange
Reaction, has synthesized the amine-modified gold nanorods of lutidines (ZD-GNRs).The lutidines that 2mL lipoic acids are modified
Amine (being dissolved in ethanol) is added slowly in the GNRs colloids (2nM) of 10mL, and 12h is stirred at room temperature, and the ZD-GNRs solution for obtaining exists
It is centrifuged three times under the rotating speed of 6000rpm, each 15min, to remove the lutidines amine that unreacted lipoic acid is modified.It
Afterwards, lutidines amine-GNR is distributed in the distilled water of 2mL.
As shown in Figure 2 a, 4) siRNA/ZD-GNRs is prepared by metal organic complex technology.First, by zinc nitrate
(5mL, 3mg/mL, 10.1mM) mixes (5mL, 2mg/mL) with lutidines amine-GNRs, and mixture is stirred at room temperature
30min.Then, 3 times (rotating speed is 5000rpm) is centrifuged, to remove unreacted raw material, the ZD-GNR that will be obtained afterwards is distributed to
In ultra-pure water.By 2uL ZD-GNR solution and 1uL siRNA (FFL siRNA (siLuc) or PLK1siRNA
(siPLK)) it is well mixed, is placed in room temperature 30min, collect siRNA/ZD-GNRs, in vitro and in vivo experiment.
5) siRNA/ZD-GNRs is estimated by agarose gel electrophoresis.By agarose (2%) be added to containing
In the Tris- acetic acid-edta buffer solution of 0.5ug/mL ethidium bromides and 2mM zinc ions, gel is obtained.20uL contains 1ug
The complex solution of siRNA is in 2% (w/v) agar containing ethidium bromide and Tris- acetic acid-EDTA (TAE) electrophoretic buffer
Electrophoresis (100V, 30min) in sugared gel.Then with LAS-3000 gel imaging systems (Japan, Fuji's life science) imaging.For
The release of assessment siRNA, 30min is processed by siRNA/ZD-GNRs with the sodium phosphate of 0.1M, and the siRNA for discharging is entered afterwards
Row imaging.
6) siRNA/ZD-GNRs gene silencing effects in the cell.Expressing luciferase stably reporter gene
143B cells containing 10% hyclone MEM medium cultures.143B cells are inoculated into 96 orifice plates, siLuc/ is used
ZD-GNRs(8μL；) and 92 μ L cell culture mediums (MEM, 10%FBS) carry out incubation 24h siRNA=10pmol.Positive control
(siLuc/LipoMAX) also synchronously carried out with the parallel laboratory test of negative control (siNC/ZD-GNRs or siNC/LipoMAX).
After being incubated 24h, the fLuc in cell is imaged with biodiversity resources system (Xenogen IVIS-100).
7) the external gene of prostate gland cancer cell/photo-thermal Synergistic treatment.Human prostate cancer cells (PC-3) are with every hole
5x103The density of individual cell is inoculated in 96 hole flat undersides, is incubated 1 day.Then, cell is washed twice with PBS, with various concentrations
SiPLK/ZD-GNRs, ZD-GNRs are 37Lower incubated cell 24h or 48h.Cell is washed with PBS again, adds 100uL fresh afterwards
Culture medium.Cell is being whether there is into 0.5W/cm respectively25min is irradiated under the laser of power, tests to detect with the CCK-8 of standard
The survival rate of tumour cell.
8) Synergistic treatment of internal gene/photo-thermal.By by 1.0x 107PC-3 cells are inoculated into the C3H/HeN of athymia
Nude mice (20-25g, Harlan, Indianapolis, IN) right rear.When the volume of tumour reaches 100-150mm3Afterwards, by salt
Water (250 μ L), the irradiation of salt solution (250 μ L)+laser, ZD-GNRs (250 μ L), the irradiation of ZD-GNRs (250 μ L)+laser, siRAN/
ZD-GNRs(250μL；SiRNA 1.5nmol) and siRNA/ZD-GNRs (250 μ L；SiRNA 1.5nmol) irradiation of+laser, lead to
Intravenous injection administration is crossed, once every three days, is administered three times altogether (every group of 4 mouse).After administration 24h, by the exposure of PC-3 tumours
In 808nm laser (0.5W/cm2) under irradiate 10min.The body weight of mouse is recorded, and by a x b2/ 2 formula calculate tumour
Volume (a and b are respectively minimum and maximum diameters).
2nd, case study on implementation
1st, as shown in Fig. 2 having obtained the GNR of homogeneous function of surface modification in the present invention.Can be with by dynamic light scattering
Find out, after the complexing of GNR and lutidines amine zinc, its average diameter has a small amount of increase, from 48.6 ± 6.8 to 51.13 ±
5.2nm, increases to 84.1 ± 8.6nm after siRNA is combined.Also, with modification step by step, surface potential reduces,
From 66.2 ± 3.4 (GNR) to 24.5 ± 5.2mV (ZD-GNR), further to 2.3 ± 1.0mV (siRNA/ZD-GNR).By with
The siRNA (siLuc) of FFL gene has carried out Ago-Gel retardance for template siRNA to siRNA/ZD-GNR
Experiment (Fig. 2).It is completely combined to form nano combined when the mol ratio of siRNA/ZD-GNR has reached 100, ZD-GNR and siRNA
Thing.In addition for siLuc/ZD-GNR compounds after phosphate is added, the complexing of siRNA and Zn/DPA is destroyed.No
Zinc ion, lutidines amine-GNRs can not be complexed with siRNA at any concentration.Result shows, the phosphorus of siRNA
It is selectively strong combination between acid molecule and the lutidines amine zinc on GNRs surfaces.
2nd, it is notable (see Fig. 3) with Gene silencing efficacy in the tumour cell of siLuc/ZD-GNRs incubations in the present invention.With
The increase of siRNA concentration, 143B tumour cells fluc expression is respectively 84.55 ± 5.32%, 57.60 ± 2.52% and 15.77
± 0.55% (now the addition of siLuc/ZD-GNRs is respectively 0.625,2.5,10pmol).ZD-GNRs passes through dimethyl pyrazole
Specificity between pyridine amine zinc ion and the phosphate anion of siRNA interacts to form the mode of compact compound to pass
SiRNA is sent, makes it by cellular uptake, and help flee from endochylema/lysosome, finally discharge siRNA molecule to cytoplasm, relied on
Its unique specific sequence gene realizes silence effect.
3rd, the gene/photo-thermal Synergistic treatment of siPLK/ZD-GNRs has been carried out in the present invention.With siPLK/ZD-GNRs, ZD-
GNRs and PBS have been incubated PC-3 24h and 48h respectively.Having washed twice and after fresh culture medium will have been changed, exist respectively
Whether there is under the irradiation of 808 laser, living cells is counted by Cell counting Kit (CCK-8).It is as shown in Figs. 4a and 4b, swash
SiPLK/ZD-GNRs under light irradiation substantially irradiates to the toxicity of PC-3 cells than the ZD-GNR under laser irradiation and without laser
SiPLK/ZD-GNRs will height.Illustrate that siPLK/ZD-GNRs has preferable gene/photo-thermal synergistic therapeutic effect to PC-3.
4th, when gross tumor volume reaches 100mm in the present invention3During left and right, respectively by ZD-GNRs and siRNA/ZD-GNRs with quiet
The mode of arteries and veins injection is administered.After administration 24h, 0.5W/cm is used2808nm laser irradiation tumour 10min, while be used for body
The thermal infrared imager of interior imaging monitors the change of its temperature.Such as Fig. 5 a, shown in b, salt solution group does not have obvious temperature change.Phase
Instead, with the mouse of ZD-GNRs and siRNA/ZD-GNRs treatment, its tumor locus temperature rises about 21 DEG C.Fig. 5 c show,
It is injected intravenously salt solution respectively to male nude mouse, after ZD-GNRs and siPLK/ZD-GNRs, in the case where laser irradiation is whether there is,
Its PC-3 tumor volume change.Control group (whetheing there is the salt solution group and the ZD-GNRs groups without laser irradiation of laser irradiation) is without aobvious
Show to the obvious suppression of tumour growth.Though the siRNA/ZD-GNRs groups irradiated without laser and the ZD-GNRs groups for having laser irradiation
The suppression to tumour growth is so shown, but gross tumor volume does not reduce.Other groups are contrasted, there is the siRNA/ that laser irradiates
ZD-GNRs groups are most effective (seeing Fig. 5 c, d) to the effect that gross tumor volume reduces.In a word, because the gene silencing induction of system is withered
The collaboration died with local photo-thermal therapy, siRNA/ZD-GNRs has very strong antitumor activity energy.
In the present invention, we by synthesize lipoic acid modify lutidines amine, and with gold nanorods combination shape
Into siRNA/ZD-GNRs compounds, under laser irradiation, it carries out gene/photo-thermal Synergistic treatment to tumour.ZD-GNRs conducts
SiRNA delivery vectors, not only form the stable nanoparticles with strong active for gene silencing, Er Qie with after siRNA complexings
Also there is the light thermal property of GNRs under laser irradiation.Additionally, gene/photo-thermal Synergistic treatments of the siPLK/ZD-GNRs to tumour
Demonstrate more preferable than single gene therapy and photo-thermal therapy effect.It is additionally, since the light acoustic performance of GNRs, siRNA/ZD-
GNRs can turn into the treatment diagnostic reagent for carrying out photoacoustic imaging and treatment simultaneously to tumour.
Claims (9)
1. the nano-complex of a kind of polynucleotide and gold nanorods, it is characterised in that consisting of s iRNA/ZD-GNRs.
2. the nano-complex of a kind of polynucleotide as claimed in claim 1 and gold nanorods, it is characterised in that the nanometer
Compound includes gold nanorods, polynucleotide and connects their organic molecule；Wherein, described organic molecule is lipoic acid
The polynucleotide carrier compound of modification, lipoic acid modification polynucleotide carrier compound and gold nanorods between be with
Body exchanges connection, for metal is organic between polynucleotides and the polynucleotide carrier compound and gold nanorods of lipoic acid modification
Complexing connection.
3. the nano-complex of a kind of polynucleotide as claimed in claim 1 and gold nanorods, it is characterised in that described
Gold nanorods include the one kind in the gold nanorods of common gold nanorods or other metals that adulterate.
4. the nano-complex of a kind of polynucleotide as claimed in claim 1 and gold nanorods, it is characterised in that described
Polynucleotide is ODN, at least one in DNA, miRNA or s iRNA.
5. a kind of preparation method of the nano-complex of polynucleotide and gold nanorods, comprises the following steps：
1) gold nanorods of surface modification cetyl trimethylammonium bromide and the polynucleotide carrier chemical combination of lipoic acid modification
Thing is by ligand exchange reaction, the amine-modified gold nanorods ZD-GNRs of synthesis lutidines：1 volume lipoic acid is modified
Polynucleotide carrier compound is added slowly in the GNRs colloids of 1-10 volumes, and 8-20h is stirred at room temperature, the diformazan for obtaining
Yl pyridines amine-GNR solution centrifugals, remove the DPA of unreacted lipoic acid modification；Afterwards, ZD-GNRs is distributed to 0.5-2 bodies
In long-pending distilled water；
2) s iRNA/ZD-GNRs are prepared by metal organic complex technology；First, by zinc nitrate and lutidines amine-
GNRs mixes, and both quality are 10-20mg/10mg, and mixture is stirred at room temperature 20-40min；Then, it is centrifuged to remove
Unreacted raw material, the ZD-GNR that will be obtained afterwards is distributed in ultra-pure water；ZD-GNR solution is mixed with polynucleotide
It is even, room temperature 20-40min is placed in, collect s iRNA/ZD-GNRs.
6. the preparation method of the nano-complex of a kind of polynucleotide as claimed in claim 5 and gold nanorods, its feature
It is：Step 1) in, the concentration of GNRs colloids is 1-10nM.
7. the preparation method of the nano-complex of a kind of polynucleotide as claimed in claim 5 and gold nanorods, its feature
It is：Step 1) in, the mixed proportion of DPA and GNRs is 400-600:1.
8. the preparation method of the nano-complex of a kind of polynucleotide as claimed in claim 5 and gold nanorods, its feature
It is：ZD-GNR is 1 with the mixed proportion of polynucleotide:10-500.
9. the nano-complex of a kind of polynucleotide as claimed in claim 1 and gold nanorods, as the gene-light of cancer
The product formulation use of hot Synergistic treatment.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710281508.7A CN106913884A (en) | 2017-04-26 | 2017-04-26 | A kind of nano-complex of polynucleotide and gold nanorods and its production and use |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710281508.7A CN106913884A (en) | 2017-04-26 | 2017-04-26 | A kind of nano-complex of polynucleotide and gold nanorods and its production and use |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN106913884A true CN106913884A (en) | 2017-07-04 |
Family
ID=59568310
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201710281508.7A Pending CN106913884A (en) | 2017-04-26 | 2017-04-26 | A kind of nano-complex of polynucleotide and gold nanorods and its production and use |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN106913884A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108261548A (en) * | 2018-01-10 | 2018-07-10 | 浙江大学 | A kind of nano-complex and its preparation method and application |
-
2017
- 2017-04-26 CN CN201710281508.7A patent/CN106913884A/en active Pending
Non-Patent Citations (6)
| Title |
|---|
| CHOI KY ET AL: "Versatile RNA interference nanoplatform for systemic delivery of RNAs", 《ACS NANO》 * |
| G LIU ET AL: "Sticky nanoparticles: a platform for siRNA delivery by a bis(zinc(II) dipicolylamine)-functionalized, self-assembled nanoconjugate", 《ANGEW CHEM INT ED》 * |
| WANG BK ET AL: "Gold-nanorods-siRNA nanoplex for improved photothermal therapy by gene silencing", 《BIOMATERIALS》 * |
| 宋娜: "金纳米棒介导的靶向沉默吲哚胺2,3-双加氧酶2（IDO2）联合光热效应治疗小鼠的黑色素瘤", 《万方数据知识服务平台》 * |
| 张卫奇 等: "纳米材料作为siRNA载体及其与细胞的相互作用研究", 《中国博士学位论文全文数据库 医药卫生科技辑 E080-20》 * |
| 杨玉东 等: "金纳米棒表面修饰技术及其功能化的研究进展", 《化工进展》 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108261548A (en) * | 2018-01-10 | 2018-07-10 | 浙江大学 | A kind of nano-complex and its preparation method and application |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Wang et al. | Carbon dots in bioimaging, biosensing and therapeutics: a comprehensive review | |
| Jia et al. | Synthesis of carbon dots from Hypocrella bambusae for bimodel fluorescence/photoacoustic imaging-guided synergistic photodynamic/photothermal therapy of cancer | |
| Liang et al. | Core-shell structured upconversion nanocrystal-dendrimer composite as a carrier for mitochondria targeting and catalase enhanced anti-cancer photodynamic therapy | |
| Gao et al. | Hybrid graphene/Au activatable theranostic agent for multimodalities imaging guided enhanced photothermal therapy | |
| Yang et al. | Carbon quantum dots: Preparation, optical properties, and biomedical applications | |
| Yao et al. | Construction of magnetic-carbon-quantum-dots-probe-labeled apoferritin nanocages for bioimaging and targeted therapy | |
| Li et al. | Core-satellite metal-organic framework@ upconversion nanoparticle superstructures via electrostatic self-assembly for efficient photodynamic theranostics | |
| CN108619511A (en) | A kind of preparation method and application of the metal organic frame drug-loading system based on cytarabine small molecule prodrugs | |
| CN104840975B (en) | A kind of super-molecule assembling body and preparation method of targeted delivery siRNA | |
| Hu et al. | Photothermal effect enhancing graphene quantum dots/semiconducting polymer/nanozyme-mediated cancer catalytic therapy | |
| Li et al. | Recent advances in photothermal and RNA interfering synergistic therapy | |
| Luan et al. | Recent near-infrared light-activated nanomedicine toward precision cancer therapy | |
| Li et al. | Nanotrains of DNA copper nanoclusters that triggered a cascade fenton-like reaction and glutathione depletion to doubly enhance chemodynamic therapy | |
| CN104840966A (en) | Nucleic acid nanometer structure anticancer compound medicine and preparation method and application thereof | |
| Tang et al. | Developing chemically modified redox-responsive proteins as smart therapeutics | |
| Hua et al. | Supramolecular vesicles based on amphiphilic pillar [n] arenes for smart nano-drug delivery | |
| Chen et al. | NIR-light-intensified hypoxic microenvironment for cascaded supra-prodrug activation and synergistic chemo/photodynamic cancer therapy | |
| Kansara et al. | Graphene quantum dots: A review on the effect of synthesis parameters and theranostic applications | |
| Li et al. | A multifunctional nanoamplifier with self-enhanced acidity and hypoxia relief for combined photothermal/photodynamic/starvation therapy | |
| Chen et al. | Polyethylenimine modified graphene oxide for effective chemo-gene-photothermal triples therapy of triple-negative breast cancer and inhibits metastasis | |
| Li et al. | Biodegradable materials with disulfide-bridged-framework confine photosensitizers for enhanced photo-immunotherapy | |
| CN106913884A (en) | A kind of nano-complex of polynucleotide and gold nanorods and its production and use | |
| Weng et al. | An Intelligent Laser‐Free Photodynamic Therapy Based on Endogenous miRNA‐Amplified CRET Nanoplatform | |
| Liu et al. | Glucose oxidase-modified metal–organic framework for starving-enhanced chemodynamic therapy | |
| CN107243000B (en) | Drug-loaded hybrid nanoparticles and preparation method 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 | ||
| WD01 | Invention patent application deemed withdrawn after publication | ||
| WD01 | Invention patent application deemed withdrawn after publication |
Application publication date: 20170704 |