CN107670053A - A kind of preparation method of the immunostimulation system based on MNPs@Au load C pG nucleic acid - Google Patents
A kind of preparation method of the immunostimulation system based on MNPs@Au load C pG nucleic acid Download PDFInfo
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Abstract
The invention discloses a kind of preparation method of the immunostimulation system based on MNPs@Au load C pG nucleic acid, the preparation method includes：（1）MNPs@Au preparation,（2）MNPs@Au surface modification,（3）CpG nucleic acid carrier systems prepare the identification of result,（4）The identification of immunostimulation system biological activity,（5）Cytotoxicity analysis.The preparation method enhances uptake rate of the cell to CpG, and improve the stability of CpG in the cell, extend the immune activation times of CpG in the cell, so that it plays good immune performance in the cell, the magnetic core heart can carry out the positioning of carrier in the cell by magnetic resonance imaging simultaneously, so that immune mechanism researchs of the CpG to cytositimulation has great application value.
Description
Technical field
The invention belongs to the medical drug delivery technologies field of nano material, and in particular to one kind is based on MNPs@Au load C pG nucleic acid
Immunostimulation system preparation method.
Background technology
Nucleic acid be by many nucleotide polymerizations into large biological molecule compound, be life one of most basic material, no
Only it is the carrier of life hereditary information, can also plays regulating and controlling effect to various complicated life processes.In recent years, diagnostic nucleic acid is treated
Method develops from basic research to clinical stage, and traditional gene diagnosis method mainly carries needs by plasmid and is transferred to
Gene carry out transgenic experiments, artificial synthesized oligonucleotides (ODN) at present, such as：Antisense D N A, aptamers
(aptamer) extensive concern and siRNA (siRNA) etc., has been caused in terms of the treatment of human diseases, these
Artificial synthesized DNA
It is generally water-soluble that preferably and cytotoxicity is extremely low, and can and the special combination of the highly sensitive height of target spot.
The unmethylated DNA rich in cytosine-guanine dinucleotides（CpG DNA）Bacterium and virus in invasion
It is widely present in genome, but CpG exists in the form of methylating in the genome of vertebrate, therefore do not methylate
CpG DNA can stimulate mammlian system to produce strong immune activation function so that panimmunity cell activation or propagation.
By research show, Toll-like receptor 9 (Toll like receptor9, TLR9) be probably CpG DNA it is intracellular by
Body, it is necessary to CpG DNA play immune activation, and after being stimulated by CpG, TLR9 can raise adaptin marrow sample point
Change the factor (MyD88), make il-1 associated kinase 4 (IRAK-4) phosphorylation, with TNF associated receptor 6
(TRAF6) interact, MAPK and nuclear Factor-Kappa B in active cell（NF-κB）Deng signal path, promote cell secretion various thin
Intracellular cytokine, including interleukin 6 (IL-6), IL-10 (IL-10), interleukin 12 (IL-12), I type interferon (typeI
) and tumor necrosis factor α (TNF-α) etc. IFNs.These cell factors can trigger B cell be divided into thick liquid cell, activation nature kill
Hinder cell, promote CD8+ cytotoxic T lymphocyte responses etc., so as to complete immune response process.
Exposed n DNA molecule carries negative electrical charge, and cell membrane surface is by negatively charged lipid bilayer group
Into, it is impossible to cell is penetrated into by cell membrane, and due to repulsive interaction of the cell to exogenous nucleic acid, into cell after easily
Degraded by serum and intracytoplasmic nuclease, be greatly limited so that nucleic acid has in the treatment use of reality, because
This, in order to strengthen the ability and improve the stability of nucleic acid molecules in the cell, it is necessary to core that nucleic acid molecules are taken in by cell membrane
Acid molecule is modified or is transported through by transport vehicle and can just be solved the above problems.
With the continuous development of nanometer biotechnology, the nano material with good characteristic has all played more in every field
Carry out more important effect, in biomedicine field, the hypotoxicity of nano material, efficient bio-compatibility and be easy to DNA modification
Etc. characteristic, play medicine as a kind of medical medicine carrying material, diagnose the transport function of nucleic acid, it is this using nano material as load
The delivery system of body, which has not only increased, carries medicine body by the intake ability of cell, while transhipment thing is played a protective role, and extends
The half-life period of transhipment medicine and nucleic acid so that the Function of medicine in vivo is improved.
The content of the invention
Technical problems to be solved：Natural artificial synthesized nucleic acid drug surface carries negative electrical charge, it is difficult to negatively charged
The cell membrane being made up of lipid bilayer of lotus is taken in, while the stability of exogenous nucleic acid in the cell is poor, easily thin
The nuclease degraded of intracellular, it is therefore desirable to can improve cellular uptake ability by a kind of and improve nucleic acid stability in the cell
Carrier, so as to play the diagnostic effect of nucleic acid drug.
Technical scheme：The invention discloses a kind of preparation side of the immunostimulation system based on MNPs@Au load C pG nucleic acid
Method, comprise the following steps：
（1）MNPs@Au preparation
By anhydrous sodium acetate and FeCl3·6H2O is added in 100mL ethylene glycol so that its final concentration is respectively 20mM ~ 50mM
With 5mM ~ 10mM, it is transferred in reactor after ultrasonic disperse 10min, 8h is reacted under conditions of 200 DEG C, takes out reactor and be allowed to nature
It is cooled to room temperature, takes out reaction product simultaneously with alternately washing 5 times of ultra-pure water and ethylene glycol, washs the sediment of last time with surpassing
Pure water is disperseed, and produces the magnetic nanometer that particle diameter is 10 ~ 30nm.
The magnetic nanometer powder 5mg newly synthesized is weighed, 100mL ultra-pure water ultrasonic disperses are added, then in the shape of stirring
The gold chloride that 5mL mass concentrations are 0.4% is added under state, adding 2 ~ 5mL mass concentrations in the state of ultrasound after stirring is
1% sodium citrate solution, continuation ultrasound are terminated by the light yellow black reaction that gradually becomes until solution colour, inhaled by magnetic field
Attached removal supernatant, and being cleaned sediment 3 times using Magneto separate with ultra-pure water, so as to obtain MNPs@Au, the thickness of golden shell for 5 ~
10nm。
（2）MNPs@Au surface modification
By 10mL steps（1）The MNPs Au solution of preparation causes particle to be separated with solution in the presence of externally-applied magnetic field, discards
Clearly, nano-particle is resuspended with 10mL pH7.2 0.01M PBSs, the concentration with ultraviolet determination nano-particle is
20nM, the CpG nucleic acid molecules of sulfydryl modification are then added, is placed under room temperature condition and reacts so that nano-particle and nucleic acid molecules
With 1:10~1:50 mol ratio is coupled, and centrifuges reactant under conditions of 8000 ~ 12000 r/min after being coupled
10min, supernatant is discarded, nano-particle is resuspended with 10mL pH7.2 0.01M PBSs；Modified then to CpG nucleic acid
Nano-particle in add TAT cell-penetrating peptide molecules, by nano-particle and cell-penetrating peptide with 1:50~1:100 mol ratio is mixed,
At room temperature after 12 ~ 24h of oscillating reactions, liquid is isolated in the presence of externally-applied magnetic field, supernatant is removed and uses 2mL ultra-pure waters
Golden nanometer particle is subjected to resuspension concentration, obtains surface modification MNPs@Au, as CpG nucleic acid carrier systems.
CpG nucleotide sequences：5’-TCCATGACGTTCCTGACGTT-AAAAA-SH-3’.
Cell-penetrating peptide sequence：GRKKRRQRRRPPQQ.
（3）CpG nucleic acid carrier systems prepare the identification of result
With the particle diameter and surface charge of several nano-particles below nanometer particle size analysis-e/or determining：MNPs@Au, the modification of CpG nucleic acid
MNPs@Au and CpG nucleic acid cell-penetrating peptide modification nano-particle.
（4）The identification of immunostimulation system biological activity
By step（2）The MNPs@Au of the surface modification of preparation mix with the RPMI-1640 cell culture mediums of 10% hyclone, make
The concentration for obtaining nano-particle is respectively 5nM, 10nM, 20nM, 50nM, is carried out as cell culture fluid and immunocyte common
It is incubated, the tumour secreted by each time point immunocyte is determined respectively at the time point for being incubated 2h, 5h, 8h, 12h, 24h, 36h
The secretion level of necrosin ＆ and interleukin-6.
（5）Cytotoxicity analysis
With MTT colorimetric methods to step（4）In cytotoxicity under four kinds of nanoparticle concentrations analyzed.
The step of preparation method of immunostimulation system of the present invention based on MNPs@Au load C pG nucleic acid（2）In
The CpG nucleic acid molecules of sulfydryl modification are 4 ~ 6h, nano-particle and the mol ratio of nucleic acid molecules coupling with MNPs@Au reaction time
For 1:30.
The preparation method step of immunostimulation system of the present invention based on MNPs@Au load C pG nucleic acid（2）In receive
The mol ratio that rice corpuscles reacts with cell-penetrating peptide is with 1:80.
The preparation method step of immunostimulation system of the present invention based on MNPs@Au load C pG nucleic acid（2）In receive
The oscillating reactions time of rice corpuscles and cell-penetrating peptide is 18h.
The preparation method step of immunostimulation system of the present invention based on MNPs@Au load C pG nucleic acid（4）In
Immunocyte is macrophage RAW264.7.
Note：The DNA molecular that the present invention uses is given birth to work biology Co., Ltd by Shanghai and synthesize, cell-penetrating peptide by gill biochemistry (on
Sea) Co., Ltd's synthesis.
Beneficial effect：The present invention is the nano material that shell is prepared for MNPs@Au with gold by core of magnetic nanometer, and
Immunostimulation system based on MNPs@Au load C pG nucleic acid is established by CpG DNA couplings and cell-penetrating peptide modification.This load
Medicine body system enhances uptake rate of the cell to CpG, and improves the stability of CpG in the cell, extends CpG in the cell
The immune activation time so that it plays good immune performance in the cell, so as to effectively avoiding clinically multiple dosing,
It will be played an important role in clinical practice.Golden shell is easy to carry out surface modification with DNA, and has good stability and life
Thing compatibility, cytotoxicity is relatively low, while the magnetic core heart can carry out the positioning of carrier in the cell by magnetic resonance imaging, so as to
So that immune mechanism researchs of the CpG to cytositimulation has great application value.
Brief description of the drawings
The grain size distribution for the MNPs@Au that Fig. 1 is MNPs@Au, MNPs@Au of CpG nucleic acid modification, CpG nucleic acid cell-penetrating peptide are modified.
Fig. 2 is the MNPs@Au and tumor necrosis factor α and interleukin-6 secretion level of various concentrations surface modification relation
Figure.Fig. 3 is the MNPs@Au of various concentrations surface modification and the graph of a relation of cell survival rate.
Embodiment
Embodiment 1
A kind of preparation method of the immunostimulation system based on MNPs@Au load C pG nucleic acid, comprises the following steps：
（1）MNPs@Au preparation
By anhydrous sodium acetate and FeCl3·6H2O is added in 100mL ethylene glycol so that and its final concentration is respectively 20mM and 5mM,
It is transferred to after ultrasonic disperse 10min in reactor, 8h is reacted under conditions of 200 DEG C, is taken out reactor and be allowed to naturally cool to room temperature,
Take out reaction product and alternately washed 5 times with ultra-pure water and ethylene glycol, the sediment for washing last time is divided with ultra-pure water
Dissipate, produce the magnetic nanometer that particle diameter is 10nm.
The magnetic nanometer powder 5mg newly synthesized is weighed, 100mL ultra-pure water ultrasonic disperses are added, then in the shape of stirring
The gold chloride that 5mL mass concentrations are 0.4% is added under state, it is 1% to add 2mL mass concentrations in the state of ultrasound after stirring
Sodium citrate solution, continue ultrasound until solution colour by it is light yellow gradually become black reaction terminate, adsorbed by magnetic field
Supernatant is removed, and is cleaned sediment 3 times using Magneto separate with ultra-pure water, so as to obtain MNPs@Au, the thickness of golden shell is 5nm.
（2）MNPs@Au surface modification
By 10mL steps（1）The MNPs Au solution of preparation causes particle to be separated with solution in the presence of externally-applied magnetic field, discards
Clearly, nano-particle is resuspended with 10mL pH7.2 0.01M PBSs, the concentration with ultraviolet determination nano-particle is
20nM, the CpG nucleic acid molecules of sulfydryl modification are then added, be placed in 4 ~ 6h of reaction under room temperature condition so that nano-particle and nucleic acid
Molecule is with 1:30 mol ratio is coupled, and centrifuges reactant under conditions of 8000 ~ 12000 r/min after being coupled
10min, supernatant is discarded, nano-particle is resuspended with 10mL pH7.2 0.01M PBSs；Modified then to CpG nucleic acid
Nano-particle in add TAT cell-penetrating peptide molecules, by nano-particle and cell-penetrating peptide with 1:80 mol ratio is mixed, in room temperature
After lower oscillating reactions 18h, liquid is isolated in the presence of externally-applied magnetic field, supernatant is removed and uses 2mL ultra-pure waters by gold nano
Particle carries out resuspension concentration, obtains surface modification MNPs@Au, as CpG nucleic acid carrier systems.
CpG nucleotide sequences：5’-TCCATGACGTTCCTGACGTT-AAAAA-SH-3’.
Cell-penetrating peptide sequence：GRKKRRQRRRPPQQ.
（3）CpG nucleic acid carrier systems prepare the identification of result
With the particle diameter and surface charge of several nano-particles below nanometer particle size analysis-e/or determining：MNPs@Au, the modification of CpG nucleic acid
MNPs@Au and CpG nucleic acid cell-penetrating peptide modification nano-particle, particle size determination result from figure as shown in figure 1, draw, MNPs@
After CpG nucleic acid and cell-penetrating peptide are progressively modified, the average grain diameter of particle gradually increases Au, so as to indicate CpG nucleic acid and wear film
Successfully the surface of nano-particle has been arrived in modification to peptide.MNPs@Au, MNPs@Au and CpG the nucleic acid cell-penetrating peptides of CpG nucleic acid modification are repaiied
The Zeta potential of the nano-particle of decorations is respectively -1.853, -1.526 ,+1.469, the results showed that MNPs@Au repair by cell-penetrating peptide
Positive charge is changed into from negative electrical charge after decorations, is more favorable for the combination of particle and cell membrane surface.
（4）The identification of immunostimulation system biological activity
By step（2）The MNPs@Au of the surface modification of preparation mix with the RPMI-1640 cell culture mediums of 10% hyclone, make
The concentration for obtaining nano-particle is respectively 5nM, 10nM, 20nM, 50nM, as cell culture fluid and macrophage RAW264.7
It is incubated jointly, the tumor necrosis factor α secreted by each time point immunocyte is determined after 24h is incubated and leucocyte is situated between
The secretion level of element -6, testing result is as shown in Fig. 2 as seen from the figure, immunostimulation of the immunostimulation system to RAW264.7
Positive effect, and stimulus intensity is larger, with the increase of nanoparticle concentration, tumor necrosis factor α and interleukin-6
Secretion level gradually increase, mainly increase with CpG content with the increase of nanoparticle concentration relevant.
（5）Cytotoxicity analysis
With MTT colorimetric methods to step（4）In cytotoxicity under four kinds of nanoparticle concentrations analyzed.Analysis result such as Fig. 3
It is shown, it is as seen from the figure, thin with the increase of nanoparticle concentration under 5nM, 10nM, 20nM, 50nM nanoparticle concentration
Downward trend is presented in born of the same parents' survival rate, but survival rate is still more than 65%, so as to illustrate this MNPs@Au load C pG nucleic acid
Immunostimulation system is smaller to the toxicity of cell, mainly due to nano-particle by reducing particle surface pair after surface modification
The toxic action of cell.
Claims (8)
1. a kind of preparation method of the immunostimulation system based on MNPs@Au load C pG nucleic acid, it is characterised in that including following step
Suddenly：
（1）MNPs@Au preparation
Magnetic nanometer core is synthesized by chemical coprecipitation, and is synthesized by the method for reduction of sodium citrate gold chloride
Gold is deposited on the surface of magnetic nanometer by golden simple substance, using magnetic nanometer is core using gold as shell so as to prepare
MNPs@Au；
（2）MNPs@Au surface modification
By 10mL steps（1）The MNPs Au solution of preparation causes particle to be separated with solution in the presence of externally-applied magnetic field, discards
Clearly, nano-particle is resuspended with 10mL pH7.2 0.01M PBSs, the concentration with ultraviolet determination nano-particle is
20nM, the CpG nucleic acid molecules of sulfydryl modification are then added, is placed under room temperature condition and reacts so that nano-particle and nucleic acid molecules
With 1:10~1:50 mol ratio is coupled, and centrifuges reactant under conditions of 8000 ~ 12000 r/min after being coupled
10min, supernatant is discarded, nano-particle is resuspended with 10mL pH7.2 0.01M PBSs；Modified then to CpG nucleic acid
Nano-particle in add TAT cell-penetrating peptide molecules, by nano-particle and cell-penetrating peptide with 1:50~1:100 mol ratio is mixed,
At room temperature after 12 ~ 24h of oscillating reactions, liquid is isolated in the presence of externally-applied magnetic field, supernatant is removed and uses 2mL ultra-pure waters
Golden nanometer particle is subjected to resuspension concentration, obtains surface modification MNPs@Au, as CpG nucleic acid carrier systems；
CpG nucleotide sequences：5’-TCCATGACGTTCCTGACGTT-AAAAA-SH-3’；
Cell-penetrating peptide sequence：GRKKRRQRRRPPQQ；
（3）CpG nucleic acid carrier systems prepare the identification of result
With the particle diameter and surface charge of several nano-particles below nanometer particle size analysis-e/or determining：MNPs@Au, the modification of CpG nucleic acid
MNPs@Au and CpG nucleic acid cell-penetrating peptide modification nano-particle；
（4）The identification of immunostimulation system biological activity
By step（2）The MNPs@Au of the surface modification of preparation mix with the RPMI-1640 cell culture mediums of 10% hyclone, make
The concentration for obtaining nano-particle is respectively 5nM, 10nM, 20nM, 50nM, is carried out as cell culture fluid and immunocyte common
It is incubated, the tumour secreted by each time point immunocyte is determined respectively at the time point for being incubated 2h, 5h, 8h, 12h, 24h, 36h
The secretion level of necrosin ＆ and interleukin-6；
（5）Cytotoxicity analysis
With MTT colorimetric methods to step（4）In cytotoxicity under four kinds of nanoparticle concentrations analyzed.
2. a kind of preparation method of immunostimulation system based on MNPs@Au load C pG nucleic acid according to claim 1,
It is characterized in that the particle diameter of described magnetic nanometer is 10 ~ 30nm.
3. a kind of preparation method of immunostimulation system based on MNPs@Au load C pG nucleic acid according to claim 1,
It is characterized in that the thickness of described golden shell is 5 ~ 10nm.
4. a kind of preparation method of immunostimulation system based on MNPs@Au load C pG nucleic acid according to claim 1,
It is characterized in that described step（2）The CpG nucleic acid molecules of middle sulfydryl modification and MNPs@Au reaction time are 4 ~ 6h, nanometer
Particle and the mol ratio of nucleic acid molecules coupling are 1:30.
5. a kind of preparation method of immunostimulation system based on MNPs@Au load C pG nucleic acid according to claim 1,
It is characterized in that described step（2）The mol ratio that middle nano-particle reacts with cell-penetrating peptide is with 1:80.
6. a kind of preparation method of immunostimulation system based on MNPs@Au load C pG nucleic acid according to claim 1,
It is characterized in that described step（2）The oscillating reactions time of middle nano-particle and cell-penetrating peptide is 18h.
7. a kind of preparation method of immunostimulation system based on MNPs@Au load C pG nucleic acid according to claim 1,
It is characterized in that described step（4）In immunocyte be macrophage RAW264.7.
A kind of 8. immunostimulation system based on MNPs@Au load C pG nucleic acid.
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108578694A (en) * | 2018-04-24 | 2018-09-28 | 武汉科技大学 | The hollow gold nanometer ball of CpG oligodeoxynucleotides modification and preparation method, application |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2011036191A2 (en) * | 2009-09-25 | 2011-03-31 | ASOCIACIÓN CENTRO DE INVESTIGACIÓN COOPERATIVA EN BIOMATERIALES - CIC biomaGUNE | Gold –coated magnetic glyconanoparticles functionalised with proteins for use as diagnostic and therapeutic agents |
| CN103952444A (en) * | 2014-05-14 | 2014-07-30 | 江南大学 | Method for using plasma nanogold dipolymer to regulate and control genetic expression in cells |
-
2017
- 2017-08-29 CN CN201710753507.8A patent/CN107670053A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2011036191A2 (en) * | 2009-09-25 | 2011-03-31 | ASOCIACIÓN CENTRO DE INVESTIGACIÓN COOPERATIVA EN BIOMATERIALES - CIC biomaGUNE | Gold –coated magnetic glyconanoparticles functionalised with proteins for use as diagnostic and therapeutic agents |
| CN103952444A (en) * | 2014-05-14 | 2014-07-30 | 江南大学 | Method for using plasma nanogold dipolymer to regulate and control genetic expression in cells |
Non-Patent Citations (4)
| Title |
|---|
| CARLOS TARIN等: "Targeted gold-coated iron oxide nanoparticles for CD163 detection in atherosclerosis by MRI", 《SCIENTIFIC REPORTS》 * |
| RUI-HUI WANG等: "TAT-Modified Gold Nanoparticle Carrier with Enhanced Anticancer Activity and Size Effect on Overcoming Multidrug Resistance", 《ACS APPLIED MATERIALS & INTERFACES》 * |
| 许海燕、王琛: "《纳米生物医学技术》", 30 June 2009, 北京：中国协和医科大学出版社 * |
| 魏敏: "基于自组装的CpG ODN-金纳米粒子多价免疫激活纳米制剂的生物学效应", 《中国科学院研究生院》 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108578694A (en) * | 2018-04-24 | 2018-09-28 | 武汉科技大学 | The hollow gold nanometer ball of CpG oligodeoxynucleotides modification and preparation method, application |
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