CN116854875A - 一种核酸响应型COFs纳米晶体材料及其制备方法和应用 - Google Patents
一种核酸响应型COFs纳米晶体材料及其制备方法和应用 Download PDFInfo
- Publication number
- CN116854875A CN116854875A CN202310827603.8A CN202310827603A CN116854875A CN 116854875 A CN116854875 A CN 116854875A CN 202310827603 A CN202310827603 A CN 202310827603A CN 116854875 A CN116854875 A CN 116854875A
- Authority
- CN
- China
- Prior art keywords
- cofs
- nucleic acid
- stranded dna
- crystal material
- rich
- 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
- 239000013310 covalent-organic framework Substances 0.000 title claims abstract description 95
- 239000000463 material Substances 0.000 title claims abstract description 62
- 239000002159 nanocrystal Substances 0.000 title claims abstract description 50
- 102000039446 nucleic acids Human genes 0.000 title claims abstract description 35
- 108020004707 nucleic acids Proteins 0.000 title claims abstract description 35
- 150000007523 nucleic acids Chemical class 0.000 title claims abstract description 35
- 230000004044 response Effects 0.000 title claims abstract description 29
- 238000002360 preparation method Methods 0.000 title claims abstract description 14
- 239000003814 drug Substances 0.000 claims abstract description 45
- 108020004414 DNA Chemical group 0.000 claims abstract description 40
- 102000053602 DNA Human genes 0.000 claims abstract description 40
- 108020004682 Single-Stranded DNA Chemical group 0.000 claims abstract description 37
- 229940079593 drug Drugs 0.000 claims abstract description 32
- 241000700605 Viruses Species 0.000 claims abstract description 20
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims abstract description 19
- 239000002773 nucleotide Substances 0.000 claims abstract description 7
- 125000003729 nucleotide group Chemical group 0.000 claims abstract description 7
- FWMNVWWHGCHHJJ-SKKKGAJSSA-N 4-amino-1-[(2r)-6-amino-2-[[(2r)-2-[[(2r)-2-[[(2r)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]piperidine-4-carboxylic acid Chemical compound C([C@H](C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCCCN)C(=O)N1CCC(N)(CC1)C(O)=O)NC(=O)[C@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 FWMNVWWHGCHHJJ-SKKKGAJSSA-N 0.000 claims abstract description 5
- 230000002401 inhibitory effect Effects 0.000 claims abstract description 5
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 24
- 239000000243 solution Substances 0.000 claims description 15
- 238000000034 method Methods 0.000 claims description 13
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 10
- 238000009833 condensation Methods 0.000 claims description 8
- 230000005494 condensation Effects 0.000 claims description 8
- 239000002953 phosphate buffered saline Substances 0.000 claims description 7
- 239000002904 solvent Substances 0.000 claims description 7
- 239000011148 porous material Substances 0.000 claims description 6
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims description 5
- MNBSXKSWDLYJHN-UHFFFAOYSA-N 2,4,6-trimethylbenzene-1,3,5-triol Chemical compound CC1=C(O)C(C)=C(O)C(C)=C1O MNBSXKSWDLYJHN-UHFFFAOYSA-N 0.000 claims description 5
- -1 aminobenzoic acid compound Chemical class 0.000 claims description 5
- 238000006243 chemical reaction Methods 0.000 claims description 5
- AUHZEENZYGFFBQ-UHFFFAOYSA-N mesitylene Substances CC1=CC(C)=CC(C)=C1 AUHZEENZYGFFBQ-UHFFFAOYSA-N 0.000 claims description 5
- 125000001827 mesitylenyl group Chemical group [H]C1=C(C(*)=C(C([H])=C1C([H])([H])[H])C([H])([H])[H])C([H])([H])[H] 0.000 claims description 5
- 229940030049 trimethylphloroglucinol Drugs 0.000 claims description 5
- RFFLAFLAYFXFSW-UHFFFAOYSA-N 1,2-dichlorobenzene Chemical compound ClC1=CC=CC=C1Cl RFFLAFLAYFXFSW-UHFFFAOYSA-N 0.000 claims description 4
- WIOZZYWDYUOMAY-UHFFFAOYSA-N 2,5-diaminoterephthalic acid Chemical compound NC1=CC(C(O)=O)=C(N)C=C1C(O)=O WIOZZYWDYUOMAY-UHFFFAOYSA-N 0.000 claims description 4
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 4
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 claims description 4
- 150000005415 aminobenzoic acids Chemical class 0.000 claims description 4
- 230000018044 dehydration Effects 0.000 claims description 4
- 238000006297 dehydration reaction Methods 0.000 claims description 4
- 239000003960 organic solvent Substances 0.000 claims description 4
- 239000000126 substance Substances 0.000 claims description 4
- 238000011068 loading method Methods 0.000 claims description 3
- 239000002994 raw material Substances 0.000 claims description 3
- IIQLVLWFQUUZII-UHFFFAOYSA-N 2-amino-5-(4-amino-3-carboxyphenyl)benzoic acid Chemical compound C1=C(C(O)=O)C(N)=CC=C1C1=CC=C(N)C(C(O)=O)=C1 IIQLVLWFQUUZII-UHFFFAOYSA-N 0.000 claims description 2
- 229960004050 aminobenzoic acid Drugs 0.000 claims description 2
- 239000007810 chemical reaction solvent Substances 0.000 claims description 2
- 238000006482 condensation reaction Methods 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims 1
- 230000035484 reaction time Effects 0.000 claims 1
- 239000003443 antiviral agent Substances 0.000 abstract description 8
- 239000002707 nanocrystalline material Substances 0.000 abstract description 8
- 239000002086 nanomaterial Substances 0.000 abstract description 7
- 102000014150 Interferons Human genes 0.000 abstract description 4
- 108010050904 Interferons Proteins 0.000 abstract description 4
- 229940079322 interferon Drugs 0.000 abstract description 4
- 210000004027 cell Anatomy 0.000 description 18
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 16
- 201000010740 swine influenza Diseases 0.000 description 10
- 206010069767 H1N1 influenza Diseases 0.000 description 8
- 241000712461 unidentified influenza virus Species 0.000 description 8
- 230000009385 viral infection Effects 0.000 description 7
- 230000000694 effects Effects 0.000 description 6
- 230000004048 modification Effects 0.000 description 6
- 238000012986 modification Methods 0.000 description 6
- 239000002585 base Substances 0.000 description 5
- 230000008685 targeting Effects 0.000 description 5
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 4
- 238000005119 centrifugation Methods 0.000 description 4
- 238000013270 controlled release Methods 0.000 description 4
- 238000002474 experimental method Methods 0.000 description 4
- 238000002329 infrared spectrum Methods 0.000 description 4
- 239000002245 particle Substances 0.000 description 4
- 239000000843 powder Substances 0.000 description 4
- 108090000623 proteins and genes Proteins 0.000 description 4
- 102000004169 proteins and genes Human genes 0.000 description 4
- 238000001179 sorption measurement Methods 0.000 description 4
- 230000003013 cytotoxicity Effects 0.000 description 3
- 231100000135 cytotoxicity Toxicity 0.000 description 3
- 238000012377 drug delivery Methods 0.000 description 3
- 238000010791 quenching Methods 0.000 description 3
- 230000000171 quenching effect Effects 0.000 description 3
- 230000004043 responsiveness Effects 0.000 description 3
- 239000000523 sample Substances 0.000 description 3
- QJEBHEQVVLFNIE-UHFFFAOYSA-N 1,3,5-trimethylcyclohexane-1,3,5-triol Chemical compound CC1(O)CC(O)(CC(O)(C1)C)C QJEBHEQVVLFNIE-UHFFFAOYSA-N 0.000 description 2
- 108010087230 Sincalide Proteins 0.000 description 2
- 108020000999 Viral RNA Proteins 0.000 description 2
- 230000000903 blocking effect Effects 0.000 description 2
- 238000010609 cell counting kit-8 assay Methods 0.000 description 2
- 238000002659 cell therapy Methods 0.000 description 2
- 230000000295 complement effect Effects 0.000 description 2
- 239000002178 crystalline material Substances 0.000 description 2
- 238000002425 crystallisation Methods 0.000 description 2
- 230000008025 crystallization Effects 0.000 description 2
- 238000013461 design Methods 0.000 description 2
- 238000010586 diagram Methods 0.000 description 2
- 239000012091 fetal bovine serum Substances 0.000 description 2
- 230000008014 freezing Effects 0.000 description 2
- 238000007710 freezing Methods 0.000 description 2
- 208000015181 infectious disease Diseases 0.000 description 2
- 230000005764 inhibitory process Effects 0.000 description 2
- 230000000670 limiting effect Effects 0.000 description 2
- 238000001000 micrograph Methods 0.000 description 2
- 239000011259 mixed solution Substances 0.000 description 2
- 229910052757 nitrogen Inorganic materials 0.000 description 2
- 238000003921 particle size analysis Methods 0.000 description 2
- 239000008188 pellet Substances 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 239000011343 solid material Substances 0.000 description 2
- 238000001228 spectrum Methods 0.000 description 2
- 238000002626 targeted therapy Methods 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- 238000002371 ultraviolet--visible spectrum Methods 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- 102000040650 (ribonucleotides)n+m Human genes 0.000 description 1
- ISCMYZGMRHODRP-UHFFFAOYSA-N 3-(iminomethylideneamino)-n,n-dimethylpropan-1-amine Chemical compound CN(C)CCCN=C=N ISCMYZGMRHODRP-UHFFFAOYSA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- 229920001661 Chitosan Polymers 0.000 description 1
- 239000003298 DNA probe Substances 0.000 description 1
- 206010059866 Drug resistance Diseases 0.000 description 1
- 229910004373 HOAc Inorganic materials 0.000 description 1
- KJHKTHWMRKYKJE-SUGCFTRWSA-N Kaletra Chemical compound N1([C@@H](C(C)C)C(=O)N[C@H](C[C@H](O)[C@H](CC=2C=CC=CC=2)NC(=O)COC=2C(=CC=CC=2C)C)CC=2C=CC=CC=2)CCCNC1=O KJHKTHWMRKYKJE-SUGCFTRWSA-N 0.000 description 1
- NQTADLQHYWFPDB-UHFFFAOYSA-N N-Hydroxysuccinimide Chemical compound ON1C(=O)CCC1=O NQTADLQHYWFPDB-UHFFFAOYSA-N 0.000 description 1
- 108091034117 Oligonucleotide Proteins 0.000 description 1
- JPYHHZQJCSQRJY-UHFFFAOYSA-N Phloroglucinol Natural products CCC=CCC=CCC=CCC=CCCCCC(=O)C1=C(O)C=C(O)C=C1O JPYHHZQJCSQRJY-UHFFFAOYSA-N 0.000 description 1
- 238000011529 RT qPCR Methods 0.000 description 1
- IWUCXVSUMQZMFG-AFCXAGJDSA-N Ribavirin Chemical compound N1=C(C(=O)N)N=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 IWUCXVSUMQZMFG-AFCXAGJDSA-N 0.000 description 1
- 239000002262 Schiff base Substances 0.000 description 1
- 150000004753 Schiff bases Chemical class 0.000 description 1
- 208000036142 Viral infection Diseases 0.000 description 1
- 238000002835 absorbance Methods 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 239000004964 aerogel Substances 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 150000001558 benzoic acid derivatives Chemical class 0.000 description 1
- 230000005540 biological transmission Effects 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
- 230000001276 controlling effect Effects 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 210000004748 cultured cell Anatomy 0.000 description 1
- 230000000120 cytopathologic effect Effects 0.000 description 1
- 238000005202 decontamination Methods 0.000 description 1
- 230000003588 decontaminative effect Effects 0.000 description 1
- 238000007872 degassing Methods 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 239000007850 fluorescent dye Substances 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 108091008147 housekeeping proteins Proteins 0.000 description 1
- 238000009396 hybridization Methods 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 125000004435 hydrogen atom Chemical class [H]* 0.000 description 1
- 238000003384 imaging method Methods 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- JTEGQNOMFQHVDC-NKWVEPMBSA-N lamivudine Chemical compound O=C1N=C(N)C=CN1[C@H]1O[C@@H](CO)SC1 JTEGQNOMFQHVDC-NKWVEPMBSA-N 0.000 description 1
- 229960001627 lamivudine Drugs 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 229960004525 lopinavir Drugs 0.000 description 1
- 239000012139 lysis buffer Substances 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 238000006011 modification reaction Methods 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 230000000737 periodic effect Effects 0.000 description 1
- QCDYQQDYXPDABM-UHFFFAOYSA-N phloroglucinol Chemical compound OC1=CC(O)=CC(O)=C1 QCDYQQDYXPDABM-UHFFFAOYSA-N 0.000 description 1
- 229960001553 phloroglucinol Drugs 0.000 description 1
- 239000013641 positive control Substances 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 230000009257 reactivity Effects 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 230000002829 reductive effect Effects 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 230000000241 respiratory effect Effects 0.000 description 1
- 238000010839 reverse transcription Methods 0.000 description 1
- 229960000329 ribavirin Drugs 0.000 description 1
- HZCAHMRRMINHDJ-DBRKOABJSA-N ribavirin Natural products O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1N=CN=C1 HZCAHMRRMINHDJ-DBRKOABJSA-N 0.000 description 1
- 239000012723 sample buffer Substances 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- IZTQOLKUZKXIRV-YRVFCXMDSA-N sincalide Chemical compound C([C@@H](C(=O)N[C@@H](CCSC)C(=O)NCC(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC=1C=CC=CC=1)C(N)=O)NC(=O)[C@@H](N)CC(O)=O)C1=CC=C(OS(O)(=O)=O)C=C1 IZTQOLKUZKXIRV-YRVFCXMDSA-N 0.000 description 1
- 239000002356 single layer Substances 0.000 description 1
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 238000010257 thawing Methods 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 229960005486 vaccine Drugs 0.000 description 1
- 238000001262 western blot Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
- C08G12/00—Condensation polymers of aldehydes or ketones with only compounds containing hydrogen attached to nitrogen
- C08G12/02—Condensation polymers of aldehydes or ketones with only compounds containing hydrogen attached to nitrogen of aldehydes
- C08G12/04—Condensation polymers of aldehydes or ketones with only compounds containing hydrogen attached to nitrogen of aldehydes with acyclic or carbocyclic compounds
- C08G12/06—Amines
- C08G12/08—Amines aromatic
-
- 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
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/4965—Non-condensed pyrazines
-
- 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
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/513—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim having oxo groups directly attached to the heterocyclic ring, e.g. cytosine
-
- 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
- A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
- A61K31/7052—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides
- A61K31/7056—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing five-membered rings with nitrogen as a ring hetero atom
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
- A61K47/54—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic compound
- A61K47/549—Sugars, nucleosides, nucleotides or nucleic acids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/69—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit
- A61K47/6949—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit inclusion complexes, e.g. clathrates, cavitates or fullerenes
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
- A61P31/16—Antivirals for RNA viruses for influenza or rhinoviruses
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Virology (AREA)
- Molecular Biology (AREA)
- Engineering & Computer Science (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pulmonology (AREA)
- Biochemistry (AREA)
- Polymers & Plastics (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
本发明公开了一种核酸响应型COFs纳米晶体材料及其制备方法和应用,属于生物纳米材料制备技术领域。所述核酸响应型COFs纳米晶体材料包括所述的富含羧基的COFs纳米晶体材料以及通过酰胺键连接其表面的单链DNA,所述单链DNA为含Cy3基团的单链DNA,所述单链DNA的核苷酸序列如SEQ ID NO:1或SEQ ID NO:2所示。本发明可将抗病毒药物或RNA干扰素等药物包载在富含羧基的COFs纳米晶体材料内部,ssDNA再通过共价键链接在富含羧基的COFs纳米晶体材料结构上,实现药物的可控释放,进而对病毒选择性识别和捕获,达到抑制病毒的目的。
Description
技术领域
本发明涉及生物纳米材料制备技术领域,特别是涉及一种核酸响应型COFs纳米晶体材料及其制备方法和应用。
背景技术
H1N1流感病毒是一种常见的呼吸道病毒,具有高传染性和高致死率,对人类健康造成了严重威胁。传统的治疗方法主要是使用抗病毒药物和疫苗,但由于病毒的易变性和耐药性等问题,治疗效果并不理想。因此,开发新型的病毒阻断策略与治疗手段对于H1N1流感病毒的防治具有重要意义。近年来随着人们对病毒感染型可控治疗系统的高度关注,纳米治疗系统因其优异的靶向性、可控性受到广泛关注。
共价有机框架(COFs)是一种具有周期性网络结构的新型有机多孔晶体材料,其主要由轻元素(如:碳、氢、氧、氮等)通过共价缩合构建而成。自2005年以来,COFs就因其优异的可设计性、独特的结构多样性、永久孔隙率和有序的孔道结构而备受关注,并被广泛应用于生物医疗领域,特别是在药物的可控释放及靶向治疗方面越来越受欢迎,这也为病毒感染的靶向治疗提供了新的机会。然而,当前COFs在病毒可控治疗方面的研究依然较少,因此,建立一种基于COFs纳米材料的智能可控型靶向治疗系统必将提高病毒感染的治疗水平,也会对患者顺应性的增加、药物副作用的降低、病毒的早期隔断及治疗等具有重大临床意义。
发明内容
本发明的目的是提供一种核酸响应型COFs纳米晶体材料及其制备方法和应用,以解决上述现有技术存在的问题,该材料可以特异识别目标RNA,具备药物可控释放性能,能有效实现病毒抑制。
为实现上述目的,本发明提供了如下方案:
本发明提供一种富含羧基的COFs纳米晶体材料,其化学式为(C14H8NO6)n,结构式如下所示:
优选的是,包括:以氨基苯甲酸类化合物与三甲酰间苯三酚为原料,通过醛胺缩合得到所述富含羧基的COFs纳米晶体材料,其中,所述氨基苯甲酸化合物与所述三甲酰间苯三酚的摩尔比为3:2。
优选的是,所述氨基苯甲酸化合物包括4,4'-二氨基-[1,1'-联苯]-3,3'-二羧酸和2,5-二氨基对苯二甲酸,但不限于此,还可为其它含有双氨基基团的苯甲酸类化合物;所述三甲酰间苯三酚为1,3,5-三甲酰间苯三酚;
所述醛胺缩合的溶剂包括邻二氯苯、正丁醇、均三甲苯或1,4-二氧六环溶剂中的一种或多种,更优选的是均三甲苯与1,4-二氧六环的混合溶液;更优选的是均三甲苯与1,4-二氧六环的溶剂体积比例为3/1,总体积为2.0mL。温度为90~150℃,更优选的是110~120℃;时间为36~120h,更优选的是,72~120h;更优选的是72h。
本发明还提供一种核酸响应型COFs纳米晶体材料,包括所述的富含羧基的COFs纳米晶体材料以及通过酰胺键连接其表面的单链DNA,所述单链DNA为含Cy3基团的单链DNA,含有30个碱基,核苷酸序列为aca acg gcg aag atg cta cag cag gtc tta(5,to3,,SEQID NO:1)。更优选的是,含有35个碱基,核苷酸序列为aca acg gcg aag atg cta cag caggtc tta aaa aa(5,to3,,SEQ ID NO:2)。
本发明还提供一种所述的核酸响应型COFs纳米晶体材料的制备方法,将所述富含羧基的COFs纳米晶体材料和所述单链DNA通过酰胺键脱水缩合而成。
优选的是,所述脱水缩合的条件为:黑暗条件下反应,反应溶剂包括甲醇、乙醇或PBS溶液,更优选的是PBS溶液;反应温度为0~50℃,更优选的是20~25℃。
本发明还提供一种负载药物的核酸响应型COFs纳米晶体材料的制备方法,将所述的富含羧基的COFs纳米晶体材料分散在含有药物的有机溶剂中,使得所述药物负载在所述富含羧基的COFs纳米晶体材料的孔道,然后再与单链DNA进行脱水缩合反应,得到负载药物的核酸响应型COFs纳米晶体材料;所述单链DNA为含Cy3基团的单链DNA,含有30个碱基,核苷酸序列为aca acg gcg aag atg cta cag cag gtc tta(5,to3,,SEQ ID NO:1)。更优选的是,含有35个碱基,核苷酸序列为aca acg gcg aag atg cta cag cag gtc tta aaa aa(5,to3,,SEQ ID NO:2)。上述药物包括抗病毒药物或者干扰素RNA,抗病毒药物T705为普适性抗病毒药物,例如:拉米夫定、利巴韦林或法匹拉韦等。
优选的是,所述负载的条件为:有机溶剂包括甲醇、丙酮或乙醇,更优选的是甲醇;温度为0~50℃,更优选的是25~30℃;时间为12~36h,更优选的是20~30h,更优选的是24h。对负载药物后的COFs纳米晶体材料提纯的过程为:将反应后的固体材料进行离心,然后用溶剂洗涤。对负载药物后的核酸响应型COFs纳米晶体材料提纯的过程为:将反应后的固体材料离心,然后用溶剂洗涤即得。
本发明还提供一种负载药物的核酸响应型COFs纳米晶体材料,其由所述的负载药物的核酸响应型COFs纳米晶体材料的制备方法制得。
本发明还提供一种所述的富含羧基的COFs纳米晶体材料,或者所述的核酸响应型COFs纳米晶体材料,或所述的负载药物的核酸响应型COFs纳米晶体材料在抑制病毒中的应用。将感染后细胞与负载药物的核酸响应型COFs纳米晶体材料(T705@DATA-COF-Por)共同孵育一段时间进行病毒阻隔,实现抑制病毒的目的。以H1N1为例,H1N1病毒阻隔体系浓度为100TCID50/mL;T705@DATA-COF-Por浓度为(50μg/mL、100μg/mL、150μg/mL)中的一种。
本发明公开了以下技术效果:
本发明通过共价缩合制备富含羧酸的COFs纳米晶体材料,并利用后修饰反应将端基为氨基的单链DNA探针引入到COFs中,实现对H1N1流感病毒RNA的识别和捕获。
本发明以所制备的核酸响应型COFs纳米晶体材料(DATA-COFs)为基础,可以将抗病毒药物或RNA干扰素等药物包载在材料内部,为抗病毒药物提供稳定、有序的孔道微环境,以实现客体药物分子的长效释放。
本发明基于核酸响应型COFs纳米晶体材料负载药物后,在细胞层面上治疗H1N1病毒感染即可实现靶向病毒及调控药物释放性能。通过COFs纳米晶体的特殊响应性释放药物,进而实现对病毒的高效抑制。
附图说明
为了更清楚地说明本发明实施例或现有技术中的技术方案,下面将对实施例中所需要使用的附图作简单地介绍,显而易见地,下面描述中的附图仅仅是本发明的一些实施例,对于本领域普通技术人员来讲,在不付出创造性劳动的前提下,还可以根据这些附图获得其他的附图。
图1为DATA-COF的合成结构图;
图2为原料及DATA-COF的IR红外谱图;
图3为DATA-COF的粉末衍射谱图;
图4为77K下DATA-COF的N2吸附曲线;
图5为DATA-COF的TEM照片;
图6为DATA-COF的DLS粒径分布谱图;
图7为T705@DATA-COF-Por的IR红外谱图;
图8为T705@DATA-COF-PorXRD的粉末衍射谱图;
图9为77K下T705@DATA-COF-Por的N2吸附曲线;
图10为T705@DATA-COF-Por的SEM照片;
图11为T705@DATA-COF-Por的DLS粒径分布谱图;
图12为药物法匹拉韦的紫外-可见光谱;
图13为药物法匹拉韦的甲醇标准曲线;
图14为T-705@DATA-COF-Por的细胞毒性谱图;
图15为T-705@DATA-COF-Por的荧光响应曲线;
图16为T-705@DATA-COF-Por的荧光恢复谱图;
图17为T-705@DATA-COF-Por的目标RNA特异性识别;T1为部分错序型ssDNA,T2和T3为完全错序型ssDNA;
图18为T-705@DATA-COF-Por的药物释放曲线;
图19为T-705@DATA-COF-Por对感染的MDCK细胞治疗后,H1N1-RNA的含量;
图20为MDCK细胞治疗后的蛋白免疫印迹图。
具体实施方式
现详细说明本发明的多种示例性实施方式,该详细说明不应认为是对本发明的限制,而应理解为是对本发明的某些方面、特性和实施方案的更详细的描述。
应理解本发明中所述的术语仅仅是为描述特别的实施方式,并非用于限制本发明。另外,对于本发明中的数值范围,应理解为还具体公开了该范围的上限和下限之间的每个中间值。在任何陈述值或陈述范围内的中间值,以及任何其他陈述值或在所述范围内的中间值之间的每个较小的范围也包括在本发明内。这些较小范围的上限和下限可独立地包括或排除在范围内。
除非另有说明,否则本文使用的所有技术和科学术语具有本发明所述领域的常规技术人员通常理解的相同含义。虽然本发明仅描述了优选的方法和材料,但是在本发明的实施或测试中也可以使用与本文所述相似或等同的任何方法和材料。本说明书中提到的所有文献通过引用并入,用以公开和描述与所述文献相关的方法和/或材料。在与任何并入的文献冲突时,以本说明书的内容为准。
在不背离本发明的范围或精神的情况下,可对本发明说明书的具体实施方式做多种改进和变化,这对本领域技术人员而言是显而易见的。由本发明的说明书得到的其他实施方式对技术人员而言是显而易见得的。本发明说明书和实施例仅是示例性的。
关于本文中所使用的“包含”、“包括”、“具有”、“含有”等等,均为开放性的用语,即意指包含但不限于。
本发明提供了一种核酸响应型COFs纳米晶体材料,可作为药物递送载体的原理为:COFs材料长程有序的孔道结构,可以为药物分子提供稳定的微环境及快速的释放通道。由富含羧基的COFs纳米晶体材料(DATA-COF)与端基为氨基的单链DNA(ssDNA)通过酰胺键链接形成。将抗病毒药物或RNA干扰素等药物包载在COFs纳米晶体材料内部,ssDNA再通过共价键链接在DATA-COF结构(DATA-COF的表面及其孔道内)上。ssDNA中的序列能与H1N1病毒碱基互补配对,从而实现对病毒的选择性识别和捕获。COFs材料为DATA-COF是未经修饰的席夫碱型共价有机框架纳米材料。本发明所制备的核酸响应型COFs纳米晶体为二维纳米材料,可以与单链DNA形成良好的π-π相互作用,ssDNA被二维材料表面吸附后,表现出荧光猝灭行为,可以用于保护药物泄露;而与双链DNA(dsDNA)的作用能力相当弱,不会发生荧光猝灭。因此,在目标H1N1病毒RNA存在的情况下,被COFs表面吸附的荧光探针ssDNA与H1N1病毒RNA形成稳定的双链后,负载在COFs材料内的药物分子正常释放,会由猝灭状态转为荧光状态。
本发明所制备的核酸响应型COFs纳米晶体材料对病毒具有抑制作用,以H1N1病毒为例,该材料可以在细胞层面上治疗H1N1病毒感染。DATA-COF表面密集包裹的ssDNA可以防止药物泄漏。当在目标RNA存在的情况下,可形成稳定的双链,用于控制释放治疗药物。COFs纳米晶体材料作为药物递送载体,核酸响应性共价有机框架纳米材料还可以通过调节材料的物理化学性质和表面化学反应性,利用核酸分子的特异性识别能力,将材料表面的核酸修饰序列设计成与H1N1流感病毒RNA互补,实现对H1N1流感病毒的识别和捕获。这种方法可以在病毒感染早期实现对病毒的快速识别和捕获,从而为治疗提供更加有力的支持。
为了对上述技术更进一步说明,下面以具体实施例方式加以说明。
实施例1DATA-COF晶体材料的制备
将2,5-二氨基对苯二甲酸(14.7mg,0.075mmol)、1,3,5-三甲酰基间苯三酚(10.5mg,0.05mmol)和HOAc(6M,0.2mL)加入均三甲苯/1,4-二氧六环(2.0mL,3/1,v/v)的混合溶液中。在液氮浴中快速冷冻并脱气,循环三次后,耐压管在120℃下加热72h。反应结束后,离心收集沉淀物,并用THF和乙醇洗涤。固体在120℃真空下干燥12h,得到黑红色晶体(DATA-COF,结构式(C14H8NO6)n,20.0mg,产率88.7%)。其中,上述1,3,5-三甲酰基间苯三酚由常规方法合成,如文献:J.Mater.Chem.A,2018,6,11140-11146(Pd loaded andcovalent-organic framework involved chitosan aerogels and their applicationfor continuous flow-through aqueous CB decontamination,J.Mater.Chem.A,2018,6,11140-11146)。
DATA-COF的合成结构式如图1所示;DATA-COF的IR红外谱图如图2所示,1705cm-1处为2,5-二氨基对苯二甲酸中羰基的伸缩振动峰;DATA-COF的XRD粉末衍射谱图,证明其具有较高的晶化程度(见图3);DATA-COF在77K下的N2吸附量为230.3cm3/g(见图4);如图5所示为TEM透射电镜图,DATA-COF形貌为纳米棒状;粒径分析证明DATA-COF的平均粒径为460.8nm(见图6)。
实施例2T705@DATA-COF-Por材料的制备
首先,将T-705(法匹拉韦,157mg,1mmol)和DATA-COF(10mg)混合在甲醇(25mL)中,28℃并搅拌24h。离心收集产物,用甲醇洗涤3次,将未负载的药物彻底清洗后,真空(60℃,12h)干燥备用。然后,将3-(3-二甲氨基丙基)碳二亚胺(3μL,30mg/mL)和N-羟基琥珀酰亚胺(1μL,100mg/mL)加入上述备用固体(100μL,1mg/mL)中,所得混合物搅拌30min,离心收集。最后,将得到的沉淀物重新分散在PBS(496μL)中,加入4μLCy3标记的ssDNA,并在黑暗中22℃摇晃24h,通过离心所得沉淀即为T-705@DATA-COF-Por。其中,上述Cy3标记的ssDNA,其序列顺序为aca acg gcg aag atg cta cag cag gtc tta(5’-3’),或aca acg gcg aag atgcta cag cag gtc tta aaa aa(5’-3’)。
T705@DATA-COF-Por的红外谱图如图7所示,1650cm-1处为酰胺键的伸缩振动峰,证明Cy3标记的ssDNA修饰成功;T-705@DATA-COF-Por的XRD粉末衍射谱图,证明单链DNA的修饰并未影响材料的晶化程度(见图8);由于单链DNA的修饰,使得T-705@DATA-COF-Por在77K下的N2吸附量下降为78.3cm3/g(见图9);如图10所示SEM扫描电镜图,T-705@DATA-COF-Por形貌依然为纳米棒状;粒径分析证明DATA-COF的平均粒径为516.6nm(见图11)。如图12和图13所示,通过紫外-可见光谱及标准曲线测得药物法匹拉韦在T-705@DATA-COF中的负载能力为9.27wt%。
实施例3T705@DATA-COF-Por的细胞毒性实验
T-705@DATA-COF-Por的细胞毒性采用CCK-8细胞计数试剂盒(Boster生物技术有限公司,武汉),每组取6个平行样本,以消除实验误差。37℃下MDCK细胞用含有不同浓度的灭菌T-705@DATA-COF-Por(40-240μg/mL)处理24h,以未处理的对应细胞作为对照。然后,每孔中加入CCK-8溶液(10μL),进一步孵育30min。每一组均以活细胞相对于对照组的百分比表示,结果表明160μg/mL以内,T-705@DATA-COF-Por具备细胞安全性(见图14)。
实施例4T705@DATA-COF-Por的目标RNA识别实验
将目标RNA(50nM)加入T-705@DATA-COF溶液(100μg/mL)中,在室温下孵育60min以充分杂交。在室温下每3min测量一次荧光,记录响应过程(Ex=525nm),如图15-图16所示,当溶液中含有目标RNA(H1N1流感病毒的RNA)时,T705@DATA-COF-Por对具有优异荧光响应性,30min即可达到较高荧光值。
实施例5T705@DATA-COF-Por的目标RNA选择性检测
将T-705@DATA-COF-Por溶液加入目标RNA(50nM)与三种错序ssDNA(50nM)溶液中,室温下孵育30min后检测其荧光(Ex=525nm),如图17所示证明T-705@DATA-COF-Por对目标RNA具有特异性识别。
实施例6T705@DATA-COF-Por的药物可控释放实验
在37℃下,将T-705@DATA-COF-Por(10mg)浸泡在100mL PBS溶液中,在规定的时间间隔内取2.0mL溶液,并用新鲜PBS代替,直到提取液中T-705的浓度保持不变。采用323nm处的紫外吸光度测定样品中T-705的浓度,以评价T-705@DATA-COF-Por对药物分子的可控释放。如图18所示,当溶液中含有目标RNA时,T705@DATA-COF-Por中的药物分子才得以释放且可以长效维持药物浓度水平,证明DATA-COF-Por对孔道中的药物分子具有控制释放的性能。
实施例7T705@DATA-COF-Por的细胞治疗实验
在24孔板中将MDCK细胞与消毒后的T-705@DATA-COF-Por或DMEM在37℃下孵育2h。接下来,25μL的H1N1(100TCID50/mL)和175μL的DMEM加入到MDCK细胞中,感染1h后去除。单层细胞分别用500μL T-705@DATA-COF-Por(0、25、50和75μg含有2%FBS胎牛血清的DMEM)或T-705(6.9μg DMEM作为阳性对照)在37℃下培养24h。用PBS洗涤3次,收集细胞,反复冻融3次,收集H1N1的RNA,逆转录后,通过qPCR检测样品细胞内的病毒含量,以证明T-705@DATA-COF-Por对感染H1N1后MDCK细胞的治疗效果。结果证明T-705@DATA-COF-Por含量与治疗效果成线性关系,相较于50μg/mL、100μg/mL及纯法匹拉韦实验组,150μg/mL的治疗效果最优(见图19)。
实施例8Western印迹
为了直观地检测病毒感染细胞的细胞病变效应,在每组培养的细胞中加入150μL的裂解缓冲液。将全细胞提取物在SDS蛋白样品缓冲液中煮沸后,对样品进行10%SDS聚丙烯酰胺凝胶电泳。最后,测定H1N1 NP蛋白的表达量,GADPH蛋白的数量代表对照的管家蛋白,如图20所示,50μg/mL的治疗组细胞中的H1N1 NP蛋白表达量最低,进一步佐证了图19的实验结果,证明T-705@DATA-COF-Por对H1N1的感染治疗具有良好效果。
从上述实施例结果数据可以看出,本发明的核酸响应型COFs纳米晶体材料可以通过表面修饰具有亲和力的分子,如抗体或寡核苷酸序列,实现对病毒的选择性捕获,这种方法可以实现对病毒的高灵敏度识别。同时,核酸响应性COFs纳米晶体材料可以作为药物递送载体,实现对H1N1流感病毒感染的治疗。本发明的核酸响应型COFs纳米晶体材料具有响应性、生物相容性、可控释放性等优点,可用于构筑基于COFs纳米材料的可控型靶向治疗系统,用作对抗病毒感染。通过核酸响应型COFs纳米晶体材料的特殊响应性释放药物,实现对病毒的高效抑制。这种方法可以提高药物的靶向性和生物利用度,从而减少药物的副作用和毒性,提高治疗效果。核酸响应型COFs纳米晶体材料在H1N1流感病毒感染的特殊成像和治疗研究中必将具有广阔的应用前景和潜在的临床应用价值。
以上所述的实施例仅是对本发明的优选方式进行描述,并非对本发明的范围进行限定,在不脱离本发明设计精神的前提下,本领域普通技术人员对本发明的技术方案做出的各种变形和改进,均应落入本发明权利要求书确定的保护范围内。
Claims (10)
1.一种富含羧基的COFs纳米晶体材料,其特征在于,其化学式为(C14H8NO6)n,结构式如下所示:
2.如权利要求1所述的富含羧基的COFs纳米晶体材料的制备方法,其特征在于,包括:以氨基苯甲酸类化合物与三甲酰间苯三酚为原料,通过醛胺缩合得到所述富含羧基的COFs纳米晶体材料,其中,所述氨基苯甲酸化合物与所述三甲酰间苯三酚的摩尔比为3:2。
3.如权利要求2所述的制备方法,其特征在于,所述氨基苯甲酸化合物包括4,4'-二氨基-[1,1'-联苯]-3,3'-二羧酸和2,5-二氨基对苯二甲酸,所述三甲酰间苯三酚为1,3,5-三甲酰间苯三酚;
所述醛胺缩合的溶剂包括邻二氯苯、正丁醇、均三甲苯或1,4-二氧六环溶剂中的一种或多种,温度为90~150℃,时间为36~120h。
4.一种核酸响应型COFs纳米晶体材料,其特征在于,包括权利要求1所述的富含羧基的COFs纳米晶体材料以及通过酰胺键连接其表面的单链DNA,所述单链DNA为含Cy3基团的单链DNA,所述单链DNA的核苷酸序列如SEQ ID NO:1或SEQ ID NO:2所示。
5.一种如权利要求4所述的核酸响应型COFs纳米晶体材料的制备方法,其特征在于,将所述富含羧基的COFs纳米晶体材料和所述单链DNA通过酰胺键脱水缩合而成。
6.如权利要求5所述的制备方法,其特征在于,所述脱水缩合的条件为:黑暗条件下反应,反应溶剂包括甲醇、乙醇或PBS溶液,反应温度为0~50℃,反应时间24h。
7.一种负载药物的核酸响应型COFs纳米晶体材料的制备方法,其特征在于,将权利要求1所述的富含羧基的COFs纳米晶体材料分散在含有药物的有机溶剂中,使得所述药物负载在所述富含羧基的COFs纳米晶体材料的孔道中,然后再与单链DNA进行脱水缩合反应,得到负载药物的核酸响应型COFs纳米晶体材料;所述单链DNA为含Cy3基团的单链DNA,所述单链DNA的核苷酸序列如SEQ ID NO:1或SEQ ID NO:2所示。
8.如权利要求7所述的制备方法,其特征在于,所述负载的条件为:有机溶剂包括甲醇、丙酮或乙醇,温度为0~50℃,时间为12~36h。
9.一种负载药物的核酸响应型COFs纳米晶体材料,其特征在于,其由权利要求7或8所述的制备方法制得。
10.一种如权利要求1所述的富含羧基的COFs纳米晶体材料,或者权利要求4所述的核酸响应型COFs纳米晶体材料,或权利要求9所述的负载药物的核酸响应型COFs纳米晶体材料在抑制病毒中的应用。
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202310827603.8A CN116854875B (zh) | 2023-07-07 | 2023-07-07 | 一种核酸响应型COFs纳米晶体材料及其制备方法和应用 |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202310827603.8A CN116854875B (zh) | 2023-07-07 | 2023-07-07 | 一种核酸响应型COFs纳米晶体材料及其制备方法和应用 |
Publications (2)
Publication Number | Publication Date |
---|---|
CN116854875A true CN116854875A (zh) | 2023-10-10 |
CN116854875B CN116854875B (zh) | 2024-01-23 |
Family
ID=88233585
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN202310827603.8A Active CN116854875B (zh) | 2023-07-07 | 2023-07-07 | 一种核酸响应型COFs纳米晶体材料及其制备方法和应用 |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN116854875B (zh) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN117771351A (zh) * | 2023-12-20 | 2024-03-29 | 山东省农业科学院畜牧兽医研究所 | 一种基于共价有机框架的猪圆环病毒ⅱ型纳米疫苗的制备方法与应用 |
Citations (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20130102545A1 (en) * | 2009-12-16 | 2013-04-25 | Magforce Ag | Temperature dependent activation of catalytic nucleic acids for controlled active substance release |
CN109261128A (zh) * | 2018-10-15 | 2019-01-25 | 西北大学 | 一种硼酸型磁性COFs材料、制备方法及其应用 |
CN110183601A (zh) * | 2019-06-18 | 2019-08-30 | 天津大学 | 一种含有酰腙键和二硫键的共价有机框架材料的制备方法及应用 |
CN110215904A (zh) * | 2019-06-14 | 2019-09-10 | 河南中医药大学 | 磁性羧基化共价有机骨架纳米复合材料及其制备方法和应用 |
IN201913002035A (zh) * | 2019-01-17 | 2020-07-24 | ||
CN112604715A (zh) * | 2020-11-27 | 2021-04-06 | 嘉兴哲夫埃特环保科技有限公司 | 一种离子交换型cof@mof/m复合材料及其制备方法 |
-
2023
- 2023-07-07 CN CN202310827603.8A patent/CN116854875B/zh active Active
Patent Citations (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20130102545A1 (en) * | 2009-12-16 | 2013-04-25 | Magforce Ag | Temperature dependent activation of catalytic nucleic acids for controlled active substance release |
CN109261128A (zh) * | 2018-10-15 | 2019-01-25 | 西北大学 | 一种硼酸型磁性COFs材料、制备方法及其应用 |
IN201913002035A (zh) * | 2019-01-17 | 2020-07-24 | ||
CN110215904A (zh) * | 2019-06-14 | 2019-09-10 | 河南中医药大学 | 磁性羧基化共价有机骨架纳米复合材料及其制备方法和应用 |
CN110183601A (zh) * | 2019-06-18 | 2019-08-30 | 天津大学 | 一种含有酰腙键和二硫键的共价有机框架材料的制备方法及应用 |
CN112604715A (zh) * | 2020-11-27 | 2021-04-06 | 嘉兴哲夫埃特环保科技有限公司 | 一种离子交换型cof@mof/m复合材料及其制备方法 |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN117771351A (zh) * | 2023-12-20 | 2024-03-29 | 山东省农业科学院畜牧兽医研究所 | 一种基于共价有机框架的猪圆环病毒ⅱ型纳米疫苗的制备方法与应用 |
Also Published As
Publication number | Publication date |
---|---|
CN116854875B (zh) | 2024-01-23 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
CN116854875B (zh) | 一种核酸响应型COFs纳米晶体材料及其制备方法和应用 | |
Qi et al. | Hydroxyapatite nanosheet-assembled porous hollow microspheres: DNA-templated hydrothermal synthesis, drug delivery and protein adsorption | |
CN107802840B (zh) | 一种基于肽类树形分子修饰荧光碳点的肿瘤微环境响应纳米粒及其制备方法 | |
Selvakumar et al. | Recent advances in the synthesis of inorganic nano/microstructures using microbial biotemplates and their applications | |
Wang et al. | Autofluorescent and pH-responsive mesoporous silica for cancer-targeted and controlled drug release | |
US11510879B2 (en) | Metal-nucleic acid nanoparticle, preparation method therefor and use thereof | |
Mianehrow et al. | Introducing a highly dispersed reduced graphene oxide nano-biohybrid employing chitosan/hydroxyethyl cellulose for controlled drug delivery | |
CN109704337B (zh) | 一种快速制备分散性良好的微米级碳球的方法 | |
CN110746599B (zh) | 具有高效基因递送能力的UV光响应性超支化聚β-氨基酯及其制备方法与应用 | |
Wang et al. | Calcium phosphate/PLGA-mPEG hybrid porous nanospheres: A promising vector with ultrahigh gene loading and transfection efficiency | |
CN113754793B (zh) | 一种苯硼酸枝接的壳寡糖衍生物及其制备方法和应用 | |
CN107137718B (zh) | 一种肽修饰的多壁碳纳米管载体及其制备方法和应用 | |
CN108659241B (zh) | 具有温度响应性、pH响应性、二氧化碳响应性的星型聚合物、自愈合水凝胶及制备方法 | |
CN105412936B (zh) | 一种刺激响应型聚吡咯纳米管靶向药物载体及制备方法 | |
Kumar et al. | Synthesis of mesoporous SiO 2–ZnO nanocapsules: Encapsulation of small biomolecules for drugs and “SiOZO-plex” for gene delivery | |
CN116239101A (zh) | 具有近红外荧光及超氧化物歧化酶活性碳点纳米酶及其制备方法和应用 | |
Ma et al. | Hierarchical porous bioactive glasses/PLGA-magnetic SBA-15 for dual-drug release | |
CN106995948B (zh) | 一种氮掺杂碳纳米点/磁性金属氧化物复合纳米纤维材料、制备方法及其应用 | |
Garland et al. | Synthesis and applications of cellulose nanohybrid materials | |
CN113248556B (zh) | 一种核酸枝接偶氮苯的组装体及制备方法及应用 | |
CN109575240B (zh) | 一种高荧光量子效率的红光聚合物及量子点溶液及用途 | |
Yahyazadeh et al. | A New Procedure for the Preparation of 3, 4-dihydropyrimidin-2 (1H)-one and Octahydroquinazolinone Derivatives catalyzed by SCMNPs@ CA-EASO3H under Solvent-free Conditions | |
CN110642968B (zh) | 双酶响应性哑铃形超两亲分子及其制备方法和用途 | |
CN111892735B (zh) | 一种表面修饰光催化剂的反应分离一体膜的制备方法及其应用 | |
CN108567982A (zh) | 一种基于介孔硅及四面体dna的载药体系 |
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 |