CN107050464A - It is a kind of to be loaded with aptamers modifying DNA nanocages of adriamycin and preparation method thereof - Google Patents
It is a kind of to be loaded with aptamers modifying DNA nanocages of adriamycin and preparation method thereof Download PDFInfo
- Publication number
- CN107050464A CN107050464A CN201610991298.6A CN201610991298A CN107050464A CN 107050464 A CN107050464 A CN 107050464A CN 201610991298 A CN201610991298 A CN 201610991298A CN 107050464 A CN107050464 A CN 107050464A
- Authority
- CN
- China
- Prior art keywords
- chains
- aptamers
- nanocages
- dna
- dna nanocages
- 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
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
- A61K31/7028—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages
- A61K31/7034—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin
- A61K31/704—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin attached to a condensed carbocyclic ring system, e.g. sennosides, thiocolchicosides, escin, daunorubicin
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Molecular Biology (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
Abstract
The invention discloses a kind of aptamers modifying DNA nanocages for being loaded with adriamycin and preparation method thereof, category medical sci-tech field.The present invention is synthesized in the oligonucleotide sequence modification of MUC1 mucin aptamers to four oligonucleotide sequences of DNA positive tetrahedron structures by nucleotide sequence, and utilize the base pair complementarity principle of nucleic acid, stable DNA positive tetrahedron structures are self-assembly of under certain condition, obtain the DNA nanocages that each summit is modified with different number MUC1 mucin aptamers, and adriamycin is loaded into by physically trapping, to reach the purpose of neoplasm targeted therapy.Experiment shows; load medicine DNA nanocages can be self-assembly of by nanocages nucleic acid backbone; without complicated preparation process; and targeting and the transmembrane transport characteristic of DNA nanocages using MUC1 mucin aptamers and realize that the efficient targeting to the cells of human breast carcinoma MCF 7 is absorbed; aptamer is protected by nuclease degradation in vivo, a kind of new drug-loading system not to be provided for the cancer target delivering of chemotherapeutics simultaneously.
Description
Technical field：
The present invention relates to a kind of cancer target aptamers modifying DNA nanocages for being loaded with adriamycin and preparation method thereof, category
In pharmaceutical technology field.
Background technology：
DNA nanocages are the nanometers being self-assembly of by a plurality of DNA oligonucleotide chains synthesized by base pair complementarity
Level three-dimensional polyhedron structure, common are tetrahedron, octahedron, triagonal bipyrimidal and dodecahedron etc..This DNA nanostructure
Self assembly have higher controllability and accuracy, make it in fields such as biology sensor, molecular imaging and nanometer calculators
Application increasingly attract attention.Wherein, positive tetrahedron DNA nanostructure has good mechanical rigid and structural stability,
Positive tetrahedron DNA nanocages are can be described as again, and the nanocages can be by the DNA oligonucleotide chains of four synthesis by quickly from group
Dress is obtained, and is easily combined with different chemical group and biomolecule and has many functions.Positive tetrahedron DNA nanocages
Four summits can contain other nucleic acid fragments, and positive tetrahedron DNA nanocages and its other nucleic acid fragments for carrying can be resisted
The degraded of nuclease, with good stability.In addition, positive tetrahedron DNA nanocages are in situation about existing without transfection reagent
Under, it can enter inside mammalian cell, and can keep relatively complete in endochylema.This characteristic makes DNA nanometers of positive tetrahedron
Cage delivers drugs into intracellular and is possibly realized as a kind of new pharmaceutical carrier.
Aptamer (aptamer, apt), referred to as fit, it is the single stranded oligonucleotide piece that a class has particular sequence
Section, can be formed by itself two, the target molecules (such as each receptoroid, mucoprotein) expressed of tertiary structure and tumor surface send out
Raw high-affinity and strong specific combination, with molecule distinguishability outstanding as antibody class.One is used as by the use of fit
The new tumor targeted molecular of class has the advantage that：1. the compatibility combined with target molecules is high, and affinity constant (Kd values) can
Up to nmol/L or pmol/L levels, the compatibility that some are fit has been even more than antibody；2. targets identification high specificity, it is fit
Its specificity is ensure that in screening process, every kind of target has the fit of its specific binding；3. it is easy to extensive synthesis, reappears
Property is good, and cost is low；4. storage stability is good, can keep stable in freeze-dried powder or solution；5. good biocompatibility, immunogenicity
It is more low.MUC1 (Mucin 1, MUC1) is mainly expressed in the cell membrane top of many secretion sexual organs under normal circumstances,
One layer of physical barriers are formed, are resisted from extraneous invasion and attack physical, chemically with pathogenic microorganism when cancer occurs for cell
After change, in all regions of cell surface all great expressions, more than 10 times up to normal cell of its expression quantity.MUC1 mucins
Abnormal change can also occur for level of glycosylation.Glycosyl transferase activity, which increases, in tumour cell causes not exclusively glycosylation, endless
Full glycosylation can cause side sugar chain length to shorten again, and tumor associated antigen epitope masked on core peptide is sudden and violent when making normal configuration
Expose, the target spot as oncotherapy.MUC1 aptamers have high affinity to MUC1 mucins, can be sticked with height expression MUC1
The receptor-specific of the tumor cell surface of albumen is combined.
Adriamycin (Doxorubicin, Dox) is a kind of conventional anti-tumor chemotherapeutic medicine, the medicine can the intercalation of DNA and suppress core
The synthesis of acid, antitumor spectra is wider, belongs to cell cycle nonspecific agent (CCNSA), has killing action to the tumour cell of various growth cycles,
The Dox formulations listed at present are based on intravenous fluid.But it is distributed widely in blood after the direct intravenously administrables of Dox and whole body is each
Tissue, can produce extensive biochemical effect, with strong toxic side effect to body.On the other hand, drug resistance of tumor
It is also the raising for limiting oncotherapy effect.Therefore, reduce dosage and improve tumour cell to chemotherapeutics Dox
Sensitiveness, be the break-through point of oncotherapy.
Therefore, positive tetrahedron DNA nanocages are combined by the present invention with fit, thin using MUC1 mucins aptamers as tumour
The targeted molecular of born of the same parents, positive tetrahedron DNA nanocages build a cancer target based on fit identification from group as pharmaceutical carrier
Fill DNA nanocages drug-loading systems.On this basis, adriamycin (Doxorubicin, Dox) is chosen as antineoplastic, is utilized
Dox can be embedded into the characteristic in nucleic acid double chain, and Dox is loaded into the nucleic acid double chain skeleton of nanocages in Non-covalent binding mode
In, realize carrying of the positive tetrahedron DNA nanocages to Dox.Using the fit targeting mediation to tumour cell, realize
The cancer target of Dox- positive tetrahedron DNA nanocages；Enter born of the same parents' ability using the endocytosis of positive tetrahedron DNA nanocages simultaneously, realize
Intracellular delivering to Dox, finally makes medicine play antitumor activity, it is to avoid or reduction is to the toxic side effect of normal cell.
The content of the invention：
The purpose of the present invention is the property for overcoming aptamer easily to be degraded in vivo by nuclease, with DNA nanocages
For carrier, there is provided nanometer formulation based on large biological molecule carrier and its preparation side with tumor-targeting of a kind of stabilization
Method.
A kind of cancer target aptamers modifying DNA nanocages for being loaded with adriamycin, positive tetrahedron (Tetrahedron) DNA
Nanocages are abbreviated as Td, and the DNA nanocages with different number aptamers are abbreviated as apt-Td, 2apt-Td, 3apt-Td,
Wherein apt-Td represents the DNA nanocages that MUC1 mucin aptamers are modified with one summit of positive tetrahedron, and 2apt-Td is represented
The DNA nanocages of MUC1 mucin aptamers are modified with two summits of positive tetrahedron, 3apt-Td represents three tops of positive tetrahedron
The DNA nanocages of MUC1 mucin aptamers are modified with point, the preparation for being loaded with Dox is abbreviated as Dox@Td, Dox@apt- respectively
Td, Dox@2apt-Td, Dox@3apt-Td.
The concrete technical scheme of the present invention is as follows：
Step 1：By consulting pertinent literature, choose can complementary pairing formation positive tetrahedron DNA nanocages 4 few nucleosides
Acidic group plinth chain, using its space structure of RNA structure software analysis, to determine four oligonucleotide chains of DNA nanocages
Sequence, respectively A chains, B chains, C chains, D chains；End modified 3 oligonucleotide chains for having a MUC1 mucin aptamers of design, point
Wei not A chains, B ' chains, C ' chains；It is respectively synthesized above-mentioned nucleotide sequence A chains, B chains, C chains, D chains, A ' chains, B ' chains and C ' chains.
Step 2：By synthetic equimolar than TM buffer (10mM can be dissolved in respectively so that four DNA of complementary pairing are single-stranded
Tris-HCl, 5mM MgCl2, pH 8.0) in, after mixing, it is put into PCR instrument, cycle of annealing is set, is brought rapidly up to 95 DEG C incubating
5~10min is educated, 4 DEG C are then cooled to rapidly, the synthesis of DNA nanocages is carried out.
Step 3：A certain amount of adriamycin is weighed, TM buffer (10mM Tris-HCl, 5mM MgCl are dissolved in2, pH
8.0) Doxorubicin solution is obtained in, the DNA nanocages and the Doxorubicin solution that are synthesized in step 1 are mixed with certain mol proportion, room
Temperature is incubated 3~6h.Incubation crosses G-100 sephadex columns to remove free Dox after terminating.Obtain final preparation.
The present invention is by the structural defence MUC1 mucin aptamers of DNA nanocages, to realize medicine to tumor tissues
Targeted delivery, reduces the toxic side effect of cancer target medicine carrying delivery system normal tissue, while by DNA nanocages in itself
Entering born of the same parents' ability helps Dox to enter born of the same parents, accumulation of the increase medicine in tumour cell and improve curative effect.
Brief description of the drawings：
Accompanying drawing 1：Step 1 gained DNA nanocages polyacrylamide gel electrophoresises in specific embodiment 1
(Polyacrylamide Gel Electrophoresis, PAGE) result
Accompanying drawing 2：Step 1 gained DNA nanocages AFM (Atomic Force in specific embodiment 1
Microscope, AFM) figure
Accompanying drawing 3：Step 2 gained 3apt-Td DNA nanocages serum stability PAGE electrophoretograms in specific embodiment 1
Accompanying drawing 4：Gained Td, apt-Td, 2apt-Td, 3apt-Td fluidic cell result figures in specific embodiment 2
Accompanying drawing 5：Gained Dox@Td, Dox@apt-Td, Dox@2apt-Td, Dox@3apt-Td are inverted in specific embodiment 3
Fluorescence microscope result figure
Embodiment：
With reference to specific embodiment, the present invention is expanded on further.It should be understood that these embodiments are merely to illustrate the present invention
Rather than limitation the scope of the present invention.In addition, it is to be understood that after the content of the invention lectured has been read, people in the art
Member can make various changes or modifications to the present invention, and these equivalent form of values equally fall within the application appended claims and limited
Scope.
Specific embodiment 1
Step 1：
Company is sent to synthesize following 7 DNA oligonucleotide chains：
A：5′-CGT ATC ACC AGG CAG TTG AGA CGA ACA TTC CTA AGT CTG AA A TTT ATC
ACC C GC CAT AGT AG-3′
B：5′-CGA TTA CAG CTT GCT ACA CGA TTC AGA CTT AGG AAT GTT CGA CAT GCG
AGG GTC CAA TAC CG-3′
C：5′-CGT GTA GCA AGC TGT AAT CGA CGG GAA GAG CAT GCC CAT CCA CTA CTA
TGG CGG GTG ATA AA-3′
D：5′-CTC AAC TGC CTG GTG ATA CGA GGA TGG GCA TGC TCT TCC CGACGG TAT
TGG ACC CTC GCA TG-3′
A′：5′-CGT ATC ACC AGG CAG TTG AGA CGA ACA TTC CTA AGT CTG AA A TTT
ATC ACC C GC CAT AGT AGTTTTTTT GCAGTTGATCCTTTGGATACCCTGG-3′
B′：5′-CGA TTA CAGCTT GCT ACA CGA TTC AGA CTT AGG AAT GTT CGA CAT GCG
AGG GTC CAA TAC CGTTTTTTT GCAGTTGATCCTTTGGATACCCTGG-3′
C′：5′-CGT GTA GCA AGC TGT AAT CGA CGG GAA GAG CAT GCC CAT CCA CTA CTA
TGG CGG GTG ATA AATTTTTTT GCAGTTGATCCTTTGGATACCCTGG-3′
A (or A '), B (or B '), C (or C '), D is single-stranded respectively with TM buffer (10mM Tris-HCl, 5mM
MgCl2, pH 8.0) and dissolve standby.Four chain equal proportions are mixed into (every chain final concentration is 250nM).Then entered with PCR instrument
Row annealing：95 DEG C of incubation 5min, are then cooled to 4 DEG C in 30s.Cancer target Self-assembled DNA nanocages carrier (Td,
apt-Td、2apt-Td、3apt-Td).It is PAGE electrophoresis knots that proof diagram 1 is carried out to structure by 6% Native PAGE and AFM
Really.Fig. 2 is AFM results.In Fig. 1, swimming lane is respectively AB, ABC, ABCD (Td), AB ' CD (apt-Td), A ' B ' CD from left to right
(2apt-Td)、A′B′C′D(3apt-Td).Shown AFM height map in Fig. 2 is exactly the table of DNA nanocages
Face structure.Two figures show that DNA nanocages are successfully prepared.
Step 2：Serum stability experiment is carried out to the 3apt-Td in step 1, the Dd matched using complete complementary is compares
Group.0.9mL PBS (pH 7.4) are pipetted in EP pipes, the hyclone (FBS) that 0.1mL does not put out a fire is added, mixes, is configured to
10%FBS is standby.With 3apt-Td and 10%FBS and Dd and 10%FBS when 0,2,4,8,12h, volume is than for 9: 1
Mix, be subsequently placed in 37 DEG C of constant temperature gas baths.At the end of setting-out, result is tested with 6% polyacrylamide gel electrophoresis
Card.Fig. 3 is stability test PAGE electrophoresis results, is as a result shown, compared with the double-strand Dd that complete complementary is matched, and the present invention is made
Standby DNA nanocages have more preferable stability.
Step 3：Accurately weighing 5.8mg Dox is dissolved in 50mL TM buffer (10mM Tris-HCl, 5mM MgCl2, pH
8.0) in, the DNA nanocages synthesized in step 1 and Dox solution is mixed by 1: 100 ratio of mol ratio, 4h is incubated at room temperature.
Incubation crosses G-100 sephadex columns to remove free Dox after terminating.Obtain final preparation.Clean EP is taken to manage, by final preparation
Dox@3apt-Td and 10%FBS is added and mixed with 5: 1 volume ratio, is placed in 37 DEG C of gas baths overnight, is destroyed DNA basket structures,
Make to contain the Dox into cage in a free form to exist.With efficient liquid phase (High-Performance Liquid
Chormatography, HPLC) measurement Dox drugloading rate, chromatographic condition is：Detection wavelength：485nm；Chromatographic column：C18 is anti-phase
Chromatographic column (Inertsil, 4.6 × 150mm, 5 μm)；Mobile phase：30% acetonitrile；Column temperature：35℃；Flow velocity：1.0mL/min；Sample introduction
Volume：20μL.3apt-Td prepared by the present invention, each basket structure can carry 50~60 Doxorubicin molecules.
Specific embodiment 2
Human liver cancer Hep G2 cells using MUC1 low expressions carry out cell in vitro intake experiment, investigate real as negative control
Apply example 1 gained Td, apt-Td, 2apt-Td, 3apt-Td cell-targeting intake ability.
By MCF-7 Human Breast Cancer Cells and human hepatoma HepG2 cell using density as 1 × 105Cells/well is inoculated in 24 holes
In plate, 24h is cultivated.Then, cell, which is used, contains sample (embodiment 1 gained Td, apt-Td, 2apt-Td and 3apt-Td, identical
Ultimate density is 1000nM) the medium treatment 5h (37 DEG C) without serum.Rinsed 3 times with fresh PBS after cell incubation 4h,
Then trypsin digestion cell is used, PBS is added after the completion of digestion cell suspension is made, crossed after miillpore filter, using flow cytometer
Cell is observed to its intake ability.As a result as shown in Figure 4.As a result show, for positive MCF-7 cells, it enters born of the same parents' ability
Increase with the increase of aptamers quantity, and for negative Hep G2 cells, the increase of aptamers quantity reduces it on the contrary
Enter born of the same parents' ability, show, 3apt-Td has preferably cell targeted.
Specific embodiment 3
Dox@Td, Dox@apt-Td, Dox@2apt-Td, the Dox@3apt-Td of the gained of instantiation 3 of the present invention are carried out
Cell in vitro intake experiment.
By MCF-7 Human Breast Cancer Cells using density as 1 × 105Cells/well is inoculated in 24 orifice plates, cultivates 24h.Then,
Cell is used containing sample (gained Dox@Td, Dox@apt-Td, Dox@2apt-Td, Dox@3apt-Td of embodiment 3, and free
Dox, identical adriamycin ultimate density be 11.6 μ g/mL) the culture medium without serum handle 1,2 and 3h (37 DEG C) respectively.
Rinsed 3 times with fresh PBS after the cell incubation set time, cell is observed to its intake ability using inverted fluorescence microscope.
As a result as shown in Figure 5.As a result show：During 1h, the cellular uptake for the adriamycin that dissociates is most strong, Dox@Td, Dox@apt-Td, Dox@
2apt-Td, Dox@3apt-Td the born of the same parents' ability that enters increase with the increase of aptamers quantity；During 2h, free adriamycin and it is loaded with
Cellular uptake difference between the DNA cages of adriamycin is obviously reduced；During 3h, almost without difference.Free adriamycin enters born of the same parents' mechanism
For Passive diffusion, enter born of the same parents comparatively fast, and DNA cages then need to be transported through by the memebrane protein of cell surface, so there is time lag.
Claims (5)
1. a kind of aptamers modifying DNA nanocages for being loaded with adriamycin, can be abbreviated as Dox@apt-Td, Dox@2apt-Td and
Dox@3apt-Td, wherein Dox are adriamycin, and apt is MUC1 mucin aptamers, and Td is positive tetrahedron DNA nanocages, wherein
Apt-Td represents the DNA nanocages that MUC1 mucin aptamers are modified with one summit of positive tetrahedron, and 2apt-Td represents positive four
The DNA nanocages of MUC1 mucin aptamers are modified with the Ti Liangge summits of face, 3apt-Td is represented on three summits of positive tetrahedron
It is modified with the DNA nanocages of MUC1 mucin aptamers.Wherein, Dox@3apt-Td, it is characterised in that each 3apt-Td cage knots
Structure can carry 50~60 Doxorubicin molecules.
2. the preparation method of the cancer target aptamers modifying DNA nanocages according to claim 1 for being loaded with adriamycin, its
It is characterised by using following steps：
Step 1：By consulting pertinent literature, choose can complementary pairing formation positive tetrahedron DNA nanocages 4 few nucleosides acidic groups
Plinth chain, using its space structure of RNA structure software analysis, with the sequence for four oligonucleotide chains for determining DNA nanocages
Row, respectively A chains, B chains, C chains, D chains；End modified 3 oligonucleotide chains for having a MUC1 mucin aptamers of design, be respectively
A ' chains, B ' chains, C ' chains；It is respectively synthesized above-mentioned nucleotide sequence A chains, B chains, C chains, D chains, A ' chains, B ' chains and C ' chains.
Step 2：By synthetic equimolar than TM buffer (10mM can be dissolved in respectively so that four DNA of complementary pairing are single-stranded
Tris-HCl, 5mM MgCl2, pH8.0) in, after mixing, it is put into PCR instrument, cycle of annealing is set, is brought rapidly up to 95 DEG C incubating
5~10min is educated, 4 DEG C are then cooled to rapidly, the synthesis of DNA nanocages is carried out.
Step 3：A certain amount of adriamycin is weighed, TM buffer (10mM Tris-HCl, 5mM MgCl are dissolved in2, pH8.0) in
To Doxorubicin solution, the DNA nanocages and the Doxorubicin solution that are synthesized in step 1 are mixed with certain mol proportion, incubation at room temperature 3~
6h.Incubation crosses G-100 sephadex columns to remove free Dox after terminating.Obtain final preparation.
3. the cancer target aptamers modifying DNA nanocages preparation method for being loaded with adriamycin according to claim 2, its
It is characterised by PCR annealing processes being incubated 5~10min at 95 DEG C, 4 DEG C is then cooled in 30s.
4. the cancer target aptamers modifying DNA nanocages preparation method for being loaded with adriamycin according to claim 2, its
Td, apt-Td, 2apt-Td are characterised by, 3apt-Td preparation concentration is 100nM~10000nM.
5. the cancer target aptamers modifying DNA nanocages preparation method for being loaded with adriamycin according to claim 2, its
The load medicine molar ratio for being characterised by DNA nanocages carrier and Doxorubicin solution is 1: 50~100.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610991298.6A CN107050464A (en) | 2016-11-09 | 2016-11-09 | It is a kind of to be loaded with aptamers modifying DNA nanocages of adriamycin and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610991298.6A CN107050464A (en) | 2016-11-09 | 2016-11-09 | It is a kind of to be loaded with aptamers modifying DNA nanocages of adriamycin and preparation method thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN107050464A true CN107050464A (en) | 2017-08-18 |
Family
ID=59618532
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201610991298.6A Pending CN107050464A (en) | 2016-11-09 | 2016-11-09 | It is a kind of to be loaded with aptamers modifying DNA nanocages of adriamycin and preparation method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN107050464A (en) |
Cited By (16)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108158999A (en) * | 2017-12-05 | 2018-06-15 | 杭州劲驰医疗器械有限公司 | HER2 targeted nanos particle, its pharmaceutical composition, preparation method and use |
| CN108187062A (en) * | 2017-12-11 | 2018-06-22 | 青岛科技大学 | A kind of construction method of the nano-medicament carrier based on nucleic acid |
| CN109260477A (en) * | 2018-10-12 | 2019-01-25 | 福州大学 | A kind of preparation method and applications of the aptamers-DNA dendroid self-assembly of high carrying capacity load medicine |
| CN109295133A (en) * | 2018-10-12 | 2019-02-01 | 福州大学 | A kind of construction method of the aptamers-DNA high molecular polymer based on nonlinear hybrid chain amplification and application |
| CN109675056A (en) * | 2019-01-02 | 2019-04-26 | 南京师范大学 | A kind of controlled release system and its preparation method and application based on base pairing rules |
| CN109745567A (en) * | 2017-11-01 | 2019-05-14 | 沈阳药科大学 | A kind of DNA fixation nano-hydrogel microballoon and its preparation and application with aptamer compound |
| CN110327308A (en) * | 2019-07-02 | 2019-10-15 | 中国药科大学 | A kind of recombination apoferritin nanocages and preparation method thereof being loaded with siRNA |
| CN112190716A (en) * | 2020-10-27 | 2021-01-08 | 四川大学 | Dynamic drug-loaded compound based on DNA tetrahedron |
| CN113750259A (en) * | 2021-08-05 | 2021-12-07 | 中南大学 | DNA nano system with targeting activation capability and construction method and application thereof |
| CN113769107A (en) * | 2021-09-16 | 2021-12-10 | 泉州师范学院 | Preparation method and application of double-targeting DNA nano drug-loaded complex |
| CN114053425A (en) * | 2021-11-11 | 2022-02-18 | 福州大学 | Nucleic acid nanometer device with cancer cell and mitochondrion dual-targeting property |
| CN114675027A (en) * | 2022-04-19 | 2022-06-28 | 南京邮电大学 | Bladder cancer protein marker activity detection kit and detection method thereof |
| CN115032258A (en) * | 2022-06-28 | 2022-09-09 | 南京邮电大学 | miRNA tumor marker detection kit |
| CN115944606A (en) * | 2023-01-09 | 2023-04-11 | 蒋彬灿 | Drug-loaded nanoparticle targeting nasopharyngeal tumor cells and preparation method and application thereof |
| CN116785445A (en) * | 2023-07-14 | 2023-09-22 | 百药智达（北京）纳米生物技术有限公司 | Targeting chemical medicine and preparation method thereof, pharmaceutical composition and application of targeting chemical medicine |
| CN117535284A (en) * | 2023-10-12 | 2024-02-09 | 大湾区大学(筹) | Tree-shaped DNA drug carrying system and preparation method and application thereof |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103160513A (en) * | 2011-12-16 | 2013-06-19 | 中国医学科学院基础医学研究所 | MUC1 protein nucleic acid aptamer, complex, composition and purposes thereof |
-
2016
- 2016-11-09 CN CN201610991298.6A patent/CN107050464A/en active Pending
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103160513A (en) * | 2011-12-16 | 2013-06-19 | 中国医学科学院基础医学研究所 | MUC1 protein nucleic acid aptamer, complex, composition and purposes thereof |
Non-Patent Citations (2)
| Title |
|---|
| BINDONG DAI ET AL: ""Aptamer-guided DNA tetrahedron as a novel targeted drug delivery system for MUC1-expressing breast cancer cells in vitro"", 《ONCOTARGET》 * |
| 郑珩等编著: "《药物生物信息学》", 30 April 2004 * |
Cited By (24)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109745567A (en) * | 2017-11-01 | 2019-05-14 | 沈阳药科大学 | A kind of DNA fixation nano-hydrogel microballoon and its preparation and application with aptamer compound |
| CN109745567B (en) * | 2017-11-01 | 2022-06-03 | 沈阳药科大学 | DNA (deoxyribonucleic acid) fixed nano hydrogel microsphere and preparation and application of DNA fixed nano hydrogel microsphere and nucleic acid aptamer compound |
| CN108158999A (en) * | 2017-12-05 | 2018-06-15 | 杭州劲驰医疗器械有限公司 | HER2 targeted nanos particle, its pharmaceutical composition, preparation method and use |
| CN108187062A (en) * | 2017-12-11 | 2018-06-22 | 青岛科技大学 | A kind of construction method of the nano-medicament carrier based on nucleic acid |
| CN108187062B (en) * | 2017-12-11 | 2020-10-02 | 青岛科技大学 | Construction method of nucleic acid-based nano-drug carrier |
| CN109260477A (en) * | 2018-10-12 | 2019-01-25 | 福州大学 | A kind of preparation method and applications of the aptamers-DNA dendroid self-assembly of high carrying capacity load medicine |
| CN109295133A (en) * | 2018-10-12 | 2019-02-01 | 福州大学 | A kind of construction method of the aptamers-DNA high molecular polymer based on nonlinear hybrid chain amplification and application |
| CN109295133B (en) * | 2018-10-12 | 2022-04-19 | 福州大学 | Construction method and application of aptamer-DNA high molecular polymer based on nonlinear hybrid chain amplification |
| CN109675056A (en) * | 2019-01-02 | 2019-04-26 | 南京师范大学 | A kind of controlled release system and its preparation method and application based on base pairing rules |
| CN109675056B (en) * | 2019-01-02 | 2022-03-18 | 南京师范大学 | Controlled release system based on base pairing rule and preparation method and application thereof |
| CN110327308A (en) * | 2019-07-02 | 2019-10-15 | 中国药科大学 | A kind of recombination apoferritin nanocages and preparation method thereof being loaded with siRNA |
| CN112190716B (en) * | 2020-10-27 | 2022-03-11 | 四川大学 | Dynamic drug-loaded compound based on DNA tetrahedron |
| CN112190716A (en) * | 2020-10-27 | 2021-01-08 | 四川大学 | Dynamic drug-loaded compound based on DNA tetrahedron |
| CN113750259A (en) * | 2021-08-05 | 2021-12-07 | 中南大学 | DNA nano system with targeting activation capability and construction method and application thereof |
| CN113769107A (en) * | 2021-09-16 | 2021-12-10 | 泉州师范学院 | Preparation method and application of double-targeting DNA nano drug-loaded complex |
| CN114053425A (en) * | 2021-11-11 | 2022-02-18 | 福州大学 | Nucleic acid nanometer device with cancer cell and mitochondrion dual-targeting property |
| CN114053425B (en) * | 2021-11-11 | 2023-03-24 | 福州大学 | Nucleic acid nanometer device with cancer cell and mitochondrion dual-targeting property |
| CN114675027A (en) * | 2022-04-19 | 2022-06-28 | 南京邮电大学 | Bladder cancer protein marker activity detection kit and detection method thereof |
| CN115032258A (en) * | 2022-06-28 | 2022-09-09 | 南京邮电大学 | miRNA tumor marker detection kit |
| CN115032258B (en) * | 2022-06-28 | 2024-01-19 | 南京邮电大学 | miRNA tumor marker detection kit |
| CN115944606A (en) * | 2023-01-09 | 2023-04-11 | 蒋彬灿 | Drug-loaded nanoparticle targeting nasopharyngeal tumor cells and preparation method and application thereof |
| CN116785445A (en) * | 2023-07-14 | 2023-09-22 | 百药智达（北京）纳米生物技术有限公司 | Targeting chemical medicine and preparation method thereof, pharmaceutical composition and application of targeting chemical medicine |
| CN116785445B (en) * | 2023-07-14 | 2024-07-16 | 百药智达（北京）纳米生物技术有限公司 | Targeting chemical medicine and preparation method thereof, pharmaceutical composition and application of targeting chemical medicine |
| CN117535284A (en) * | 2023-10-12 | 2024-02-09 | 大湾区大学(筹) | Tree-shaped DNA drug carrying system and preparation method and application thereof |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN107050464A (en) | It is a kind of to be loaded with aptamers modifying DNA nanocages of adriamycin and preparation method thereof | |
| Odeh et al. | Aptamers chemistry: Chemical modifications and conjugation strategies | |
| Wang et al. | Cell-penetrating peptide and transferrin co-modified liposomes for targeted therapy of glioma | |
| Li et al. | Recent advances in targeted drug delivery strategy for enhancing oncotherapy | |
| Kim et al. | Highly tumor-specific DNA nanostructures discovered by in vivo screening of a nucleic acid cage library and their applications in tumor-targeted drug delivery | |
| Xia et al. | Delivery of doxorubicin for human cervical carcinoma targeting therapy by folic acid-modified selenium nanoparticles | |
| CN101942445B (en) | Nucleic acid aptamer derivative and application thereof in preparation of medicament carrier | |
| Guan et al. | Uptake and transport of a novel anticancer drug-delivery system: lactosyl-norcantharidin-associated N-trimethyl chitosan nanoparticles across intestinal Caco-2 cell monolayers | |
| Linhardt et al. | Biodegradable polyphosphazene based peptide-polymer hybrids | |
| CN104151559B (en) | Polyacrylamide-acrylonitrile-Polyethylene Glycol and synthetic method and application | |
| Bi et al. | Gene-silencing effects of anti-survivin siRNA delivered by RGDV-functionalized nanodiamond carrier in the breast carcinoma cell line MCF-7 | |
| Jiang et al. | Comparison of two kinds of nanomedicine for targeted gene therapy: premodified or postmodified gene delivery systems | |
| CN105055375B (en) | Adriamycin and resveratrol with the effect of anti-multidrug resistance deliver nanoscale medicine delivery system altogether | |
| Iacobazzi et al. | Microfluidic-assisted preparation of targeted ph-responsive polymeric micelles improves gemcitabine effectiveness in pdac: In vitro insights | |
| Guan et al. | DNA nanodevice-based drug delivery systems | |
| Long et al. | Bacterial magnetosomes-based nanocarriers for co-delivery of cancer therapeutics in vitro | |
| CN105999299A (en) | Small-molecular micelle drug-loaded nano-system, as well as preparation method and application thereof | |
| CN105859990B (en) | The polymer of side chain sulfur-bearing caprylyl, its preparation method and polymer vesicle prepared therefrom and its application | |
| Kim et al. | Polymer/aptamer-integrated gold nanoconstruct suppresses the inflammatory process by scavenging ROS and capturing pro-inflammatory cytokine TNF-α | |
| Bourgat et al. | Enzyme-responsive nanoparticles and coatings made from alginate/peptide ciprofloxacin conjugates as drug release system | |
| Nelissen et al. | Improving breast cancer treatment specificity using aptamers obtained by 3D cell-SELEX | |
| Zhang et al. | Affibody modified G-quadruplex DNA micelles incorporating polymeric 5-Fluorodeoxyuridine for targeted delivery of curcumin to enhance synergetic therapy of HER2 positive gastric cancer | |
| Li et al. | Polymeric DNA hydrogels and their applications in drug delivery for cancer therapy | |
| Yang et al. | Folate and borneol modified bifunctional nanoparticles for enhanced oral absorption | |
| Vasey et al. | Polymer pro-drug nanoparticles for sustained release of cytotoxic drugs evaluated in patient-derived glioblastoma cell lines and in situ gelling formulations |
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 |
Application publication date: 20170818 |
|
| WD01 | Invention patent application deemed withdrawn after publication |