CN109718382A - A kind of preparation method of Nano medication, thus obtained Nano medication and its application - Google Patents
A kind of preparation method of Nano medication, thus obtained Nano medication and its application Download PDFInfo
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Abstract
The present invention relates to a kind of preparation methods of Nano medication, including the amphipathic nature block polymer that hydrophilic segment is contained carboxyl and dewatering medicament by being self-assembly of medicament-carried nano micelle；Medicament-carried nano micelle and silane coupling agent containing sulfydryl or disulfide bond react the first organic silicon nano hydridization micella of sulfydryl and carboxyl difunctionalization that obtain disulfide bond doping；First organic silicon nano hydridization micella obtains the second organic silicon nano hydridization micella of polyethylene glycol and carboxyl difunctionalization by oxidation reaction；Second organic silicon nano hydridization micella reacts to obtain the Nano medication of polyethylene glycol and polyethyleneimine difunctionalization by amide.The invention further relates to thus obtained Nano medication and its applications.The first order response of Nano medication according to the present invention can promote enrichment and delay of the Nano medication to tumour, and second level response can promote the responsiveness of anticancer drug to discharge, realize more efficient chemotherapy.
Description
Technical field
The present invention relates to nano biological field of medicaments, relate more specifically to a kind of preparation method of Nano medication, thus obtain
The Nano medication arrived and its application.
Background technique
In recent years, the self assembly behavior using amphipathic nature block polymer in water will have the hydrophobicity for the treatment of function
Chemotherapeutics support in its hydrophobic inner core realize chemotherapy of tumors increasingly cause researchers concern (Biomaterials,
2017,113,243-253；ACS Appl.Mater.Interfaces,2015,7,9211-9227；Adv.Mater.,2017,
29,1702342).Although these Nano medications improve tumour inhibiting rate by the infiltration of enhancing and retention effect (EPR) and reduce malicious pair
Effect, but due to the presence of multi-biological barrier especially bloodtumorbarrier, common Nano medication is still not enough to improve to swollen
The accumulation and drug-loading efficiency (Clin.Cancer.Res., 2016,22,5287) at tumor position.
It is reported that the properties such as the size of Nano medication, shape and surface charge, which transport efficiency to drug, plays crucial work
With, especially played in terms of blood circulation ability, tumor retention different abilities (Angew.Chem., 2018,
130,2641-2645；Adv.Mater.,2015,27,6450-6456；Biomacromolecules,2017,18,1449-
1459；Biomaterials,2018,161,292-305).And traditional nanometer medicine-carried system is difficult to take into account extension blood circulation
Time and raising tumour bioaccumulation efficiency.For example, neutral nanoparticle and electronegative nano particle and positively charged nano particle
It compares, the infiltration and retentivity with longer circulation time in blood circulation, but to tumor tissues then will be weaker than band just
The nano particle of electricity；And positively charged nano particle to cell membrane have very strong suction-operated, into cell after can flee from it is molten
The capture of enzyme body, but this behavior is easier to be removed in blood circulation to the no selectivity of cell so as to cause it
(Nat.Biotechnol.,2015,33,941-951).One kind is thus constructed to be able to extend blood circulation time while and mentioning swollen
The nanometer medicine-carried system of tumor accumulation is still faced with huge challenge.
In order to solve this problem, variable dimension based on pH, temperature and redox environment, charge is transformable receives
Rice medicine-carried system is devised.Wherein, due to redox potential between tumour cell, tumor microenvironment and normal tissue
The disulfide bond of greatest differences, redox response is widely used in nanometer medicine-carried system.Disulfide bond is opposite in extracellular environment
It is more stable, and be then easy that sulfydryl-two occurs with the glutathione (GSH) of overexpression in the stronger tumour cell of reproducibility
Sulfide linkage exchange reaction and be broken.For example, 2016, camptothecine and cyanine dye are prepared for one by the way that disulfide bond is bonded by Ye et al.
Kind of novel prodrugs Cy-S-CPT, it can be activated by GSH raw in tumour achieve the effect that it is antitumor (Chem.Sci.,
2016,7,4958-4965)；2017, Zhao et al. synthesized a kind of novel redox responsiveness micella C16-SS-CS-
MPEG, it can be destroyed to realize the controlled release of drug under reducing condition by dithiothreitol (DTT) (DTT)
(Int.J.Nanomed.,2017,12,2489-2504).But the nano drug-carrying with redox response reported at present
System only realizes the controlled release of drug in tumour cell, but has ignored the objects such as GSH in tumor microenvironment and blood circulation
The concentration difference of matter, and this difference is to raising high-permeability and retention effect (enhanced permeability and
Retention effect, EPR effect) so oncotherapy effect play very important effect.
Summary of the invention
For the concentration difference of the substances such as tumor microenvironment and blood circulation GSH-PX activity, the present invention is intended to provide a kind of
The preparation method of Nano medication, thus obtained Nano medication and its application.
A kind of preparation method of Nano medication of the present invention, includes the following steps: S1, and hydrophilic segment is contained carboxyl
The amphipathic nature block polymer and dewatering medicament of (- COOH) are by being self-assembly of medicament-carried nano micelle, wherein dewatering medicament quilt
It is wrapped in the inside of micella；S2, medicament-carried nano micelle and the silane coupling agent containing sulfydryl or disulfide bond react to obtain disulfide bond
Doping, sulfydryl and carboxyl difunctionalization the first organic silicon nano hydridization micellaWherein, containing sulfydryl
Or the silane coupling agent of disulfide bond enters the inside of micella and polycondensation is hydrolyzed using micella as template to deposit disulfide bond doping
Organic oxidation silicon layer；S3, the first organic silicon nano hydridization micellaPolyethylene glycol is obtained by oxidation reaction
With the second organic silicon nano hydridization micella of carboxyl difunctionalizationWherein, the first organic silicon nano hydridization
MicellaThe sulfydryl (- SH) on surface is carried out with polyethylene glycol (PEG) by disulfide bond bonded；S4, second is organic
Silicon nano hybridization micellaReact to obtain receiving for polyethylene glycol and polyethyleneimine difunctionalization by amide
Rice drugWherein, the second organic silicon nano hydridization micellaSurface carboxyl (-
COOH it) is carried out with polyethyleneimine (PEI) by amido bond bonded.
Nano medication provided by the invention is with good stability in blood circulation, and the disulfide bond of bonded PEG can be with
It is opened by the low concentration GSH of tumor microenvironment, causes PEG chain segment to fall off, PEI segment is exposed to surface, to make Nano medication
Surface conversion is positive charge, promotes tumour cell endocytosis；After Nano medication enters tumour cell, tumour cell overexpression
GSH can destroy the disulfide bond of organic oxidation silicon layer, and organic oxidation silicon layer is promoted to degrade, and the dewatering medicament contained is caused to be sustained,
Achieve the effect that antitumor.That is, Nano medication provided by the invention is a kind of organosilicon and micella (organosilicon/micella)
Base nano hybridization particle has the ability of the response of redox step by step, can effectively improve Nano medication in tumor tissues
Enrichment and it is detained, in advance leakage of the drug in vivo in cyclic process is prevented, so that it is guaranteed that reduction of the drug in tumor tissues
Property response release, thus improve tumor accumulation ability, enhancing antitumous effect, for tumour highly effective and safe treat.
Preferably, in the step S1, block copolymer and dewatering medicament are carried by the method preparation that nanometer is co-precipitated
Medicine nano-micelle.Specifically, block copolymer and dewatering medicament are dissolved in organic solvent, and deionized water is added, and are formed load medicine and are received
The aqueous solution of rice glue beam.In a preferred embodiment, block copolymer is the polycaprolactone-block- polyacrylic acid of anionic
(PCL-b-PAA), medicament-carried nano micelle PCL-b-PAA micella is thus obtained.It is highly preferred that block copolymer is PCL90-b-
PAA17.In a preferred embodiment, dewatering medicament is hydroxycamptothecin or curcumin.In fact, being not involved in subsequent modified
Journey, i.e., do not include sulfydryl, disulfide bond, amino and carboxyl fat-soluble medicine all can serve as dewatering medicament for the present invention in.
Preferably, the mass ratio of block copolymer and dewatering medicament is 10:(3~9)；The quality of block copolymer in organic solvent is dense
Degree is 0.5-2mg/mL；The volume ratio of water and organic solvent is (4~8): 1.In a preferred embodiment, organic solvent is
N,N-dimethylformamide (DMF) and/or tetrahydrofuran (THF).
Preferably, in the step S2, medicament-carried nano micelle is under the conditions of weak base and silane coupling agent reacts to obtain
One organic silicon nano hydridization micellaPreferably, silane coupling agent is 3-mercaptopropyi trimethoxy silane
(MPTMS).Wherein, oxydrolysis polycondensation reaction obtains the organic oxidation silicon layer of disulfide bond doping to MPTMS at room temperature.Preferred
Embodiment in, ammonium hydroxide or triethylamine is added into the aqueous solution of medicament-carried nano micelle to provide weak base condition to obtainAqueous solution.Preferably, the adding proportion of ammonium hydroxide/triethylamine and MPTMS are (40~100 μ L): 10mg.Having
In the embodiment of body, the additional amount of ammonium hydroxide is 100-1000 μ L；The additional amount of MPTMS is 40-100 μ L.
Preferably, in the step S3, the first organic silicon nano hydridization micellaWith it is mercapto-functionalized
Polyethylene glycol (mPEG-SH) the second organic silicon nano hydridization micella is obtained by oxidation reactionTo logical
Cross disulfide bond key joint long chain PEG.In a preferred embodiment, toAqueous solution in mPEG-SH and simple substance is added
Iodine (I2) to obtainAqueous solution.Preferably, the mass ratio of mPEG-SH and block copolymer is not less than 6:1.
The molecular weight of mPEG-SH is 5000-20000.In the particular embodiment, the mole of mPEG-SH is 6 × 10-3Mmol, I2's
Mole is 6 × 10-3mmol。
Preferably, in the step S4, the second organic silicon nano hydridization micellaAnd polyethyleneimine
Amine (PEI) amide reacts to obtain Nano medicationTo pass through the bonded short chain PEI of amido bond.Preferred real
It applies in example, toAqueous solution in PEI, carbodiimides (EDCI) and N- hydroxy thiosuccinimide is added
(NHS-Sulfo), it reacts to obtain by amideAqueous solution.Preferably, toAqueous solution
It is middle 2-morpholine ethane sulfonic acid (MES) is added, sodium hydroxide (NaOH), sodium chloride (NaCl) be configured to pH5.2-5.4 MES buffering it is molten
Liquid sequentially adds PEI, EDCI, NHS-Sulfo and obtainsPreferably, PEI and carboxyl in block copolymer
Molar ratio is controlled in (0.25~3): 1.In the particular embodiment, the mole of PEI, EDCI, NHS-Sulfo are respectively 1.5-
18μmol.Wherein, the inventory of EDCI and NHS-Sulfo is not less than the mole of carboxyl.
The present invention also provides a kind of according to Nano medication obtained by the above method.
The present invention provides a kind of application according to above-mentioned Nano medication again, wherein the bonded poly- second two of the Nano medication
The disulfide bond of alcohol (PEG) is opened by the first concentration (low concentration) glutathione (GSH), the organic oxidation silicon layer of the Nano medication
Disulfide bond is opened by the second concentration (high concentration) glutathione (GSH), and the first concentration is less than the second concentration.Particularly, first is dense
Degree is 2~20 μM, and the second concentration is 10mM.Specifically, which can respond in redox step by step, effectively improve nanometer
Drug and can utilize the responsiveness controlled release in tumour reproducibility microenvironment hydrophobic in the enrichment and delay of tumor tissues
Drug.
In short, experiment condition of the invention is mild, it is reproducible.Due to not being related in the required experiment condition of the present invention
High temperature and strong acid and strong base environment, reaction is mild, and identical result can be obtained in easy to operate, multiplicating experiment；What reaction obtained
Nano medication has redox responding ability step by step.Specifically, the first order response include: can be low outside tumor tissue cell
PEG is set to fall off under concentration GSH effect, positively charged PEI exposure promotes cell endocytic；Second level response includes: in tumour cell
The organic oxidation silicon layer degradation for adulterating disulfide bond under interior high concentration GSH effect, drug release.Finally realize the gradient of GSH
Redox responsiveness process.The first order response of Nano medication according to the present invention can promote Nano medication to the richness of tumour
Collection and delay, second level response can promote the responsiveness of anticancer drug to discharge, realize more efficient chemotherapy.
Detailed description of the invention
Fig. 1 is the process flow chart of the preparation method of Nano medication according to a preferred embodiment of the present invention；
Fig. 2 a- Fig. 2 d is the PCL-b-PAA of embodiment 1,Pass through
The particle diameter distribution statistical chart that dynamic light scattering (DLS) measures；
Fig. 3 shows the PCL-b-PAA of embodiment 1,Zeta
Current potential；
Fig. 4 is the PCL-b-PAA of embodiment 1,Fourier
Resonate infrared spectrum comparison diagram；
Fig. 5 is the PCL-b-PAA of embodiment 1,Raman light
Compose comparison diagram；
Fig. 6 shows embodiment 1Zeta potential value after being handled 2 hours with various concentration GSH；
Fig. 7 is the different length PEG modification of embodiment 2 The grain size distribution grain size distribution measured by dynamic light scattering (DLS)；
Fig. 8 a- Fig. 8 f is the different PEI modification amounts of embodiment 3 Images of transmissive electron microscope；
Fig. 9 shows the C6@of embodiment 4Cell incubation is different after 20 μM of GSH are pre-processed 2 hours
The cell fluorescence intensity of time changes；
Figure 10 is the HCPT@of embodiment 5To Hepatocellular carcinoma cell line and to l cell
The cytotoxicity figure of NIH-3T3.
Specific embodiment
With reference to the accompanying drawing, presently preferred embodiments of the present invention is provided, and is described in detail.
As shown in Figure 1, preparation method according to the present invention select block copolymer polycaprolactone-b- polyacrylic acid with it is hydrophobic
Drug obtains the nanometer of the block copolymer polycaprolactone-b- polyacrylic acid of load dewatering medicament by the method that nanometer is co-precipitated
Micella, then interact to obtain disulfide bond doping, sulfydryl/carboxylic with silane coupling agent mercaptopropyi trimethoxy silane by it
The organic silicon nano composite micelle of base difunctionalization obtains polyethylene glycol/carboxyl pair by oxidation reaction with mercapto-polyglycol
The nano combined micella of functionalization, with polyethyleneimine by amide react to obtain polyethylene glycol/polyethyleneimine difunctionalization,
Nano combined micella with graded oxidation reduction response, i.e. Nano medication.
Embodiment 1
By 10mg PCL90-b-PAA17It is dissolved in 5mL n,N-Dimethylformamide (DMF), is added until completely dissolved
40mL deionized water.0.1mL NH is added3·H2O and 0.04mL MPTMS, stirring at normal temperature is for 24 hours.The solution being stirred is transferred to
In the bag filter that molecular cut off is 14000, and a water-dialyzing is replaced every 4~6h, dialysed 48h or more the time, organic
Solvent, ammonium hydroxide, the drug of unentrapped and unreacted MPTMS are removed, and are obtainedTo gainedIn
60mg mPEG-SH (M.W.=10000) and 2mg I is added2, react and obtain for 24 hoursMES, NaCl configuration is added
At MES buffer solution, pH to 5.2 or so is adjusted with NaOH, 6 μm of ol EDCI, NHS-Sulfo, PEI (M.W.=600) are added,
It is stirred to react for 24 hours, dialyses for 24 hours to remove small molecule, obtain final
The average grain diameter that Fig. 2 a shows PCL-b-PAA micella is 113.4nm, and Fig. 2 b is shown It is flat
Equal partial size is 116.5nm, and Fig. 2 c is shownAverage grain diameter be 140.2nm, Fig. 2 d showsAverage grain diameter be 162.3nm.Obviously, as surface is gradually modified, partial size is gradually increased.
As shown in figure 3, the zeta current potential of PCL-b-PAA micella is -20.8mV,Zeta current potential be-
46.6mV,Zeta current potential be -29.9mV,Zeta current potential be 12.7mV.Obviously, with
Surface only has the PCL-b-PAA micellar phase ratio of-COOH,Show more negative current potential, it was demonstrated that its surface-SH with-
COOH coexists；WithCompared to more leveling off to 0, it was demonstrated that PEG is keyed to behind surface to surface charge
Play certain shielding action；It is positively charged, illustrate amino positively charged after PEI is reacted with carboxyl instead of
Electronegative carboxyl.
Fig. 4 and Fig. 5 shows PCL-b-PAA micella,Fu in
Leaf resonance infrared spectroscopy (FTIR spectrum) and Raman spectrum (Raman spectrum).The results show that compared to PCL-b-PAA micella,There is Si-O (1130cm in FTIR spectrum in sample-1) ,-SH (2569cm in FTIR, Raman spectrum-1)、-
SS- (the 509cm in Raman spectrum-1) characteristic peak, it was demonstrated that the oxydrolysis polycondensation of MPTMS forms the organic of disulfide bond doping
Silica skeleton, and there are mercapto functional groups；Sample 2569cm in FTIR spectrum and Raman spectrum-1Place
Sulfydryl characteristic peak disappear, and in FTIR spectrum 1105cm-1There is the peak of C-O key in position, it was demonstrated that mercapto-functionalized poly- second
Glycol withSulfydryl oxidation reaction has occurred, polyethylene glycol is keyed to material surface by disulfide bond；1637cm in the FTIR spectrum of sample-1There is the characteristic peak of amido bond in place, it was demonstrated that PEI is reacted by amide
It is bonded with carboxyl.
Fig. 6 is finalZeta potential after various concentration GSH is handled 2 hours.As a result it indicates, joins
It is pretreated according to the GSH concentration (2~20 μM) in tumor extracellular matrixCurrent potential increases, it was demonstrated that PEG falls off,
Shielding action weakens, PEI exposes；And handled referring to GSH concentration (10mM) in tumour cellCurrent potential drops instead
It is low, it may be possible to since a large amount of GSH is adsorbed onto nano grain surface by PEI, to show negative electrical charge.
Embodiment 2
Implementation method and basic recipe are same as Example 1, only change feed intake mPEG-SH molecular weight (5k, 10k,
20k), the mole that feeds intake is maintained at 6 μm of ol, finally obtains different length PEG modification
Fig. 7 is different length PEG modificationGrain
Diameter distribution map.Obviously, as PEG molecular weight increases, the partial size of gained nano material is increased with it.
Embodiment 3
Implementation method and basic recipe are same as Example 1, only change the PEI reacted with carboxyl inventory (1.5,
3,6,9,12,18 μm of ol), finally obtain different PEI modification amounts
Fig. 8 a- Fig. 8 f is different PEI modification amounts Images of transmissive electron microscope.Obviously, nano material is being modified not
Too big variation will not both topographically occur when same amount PEI.
Embodiment 4
By 10mg PCL90-b-PAA175mL N, N- dimethyl formyl are dissolved in fluorescent marker 0.2mg coumarin 6 (C6)
In amine (DMF), 40mL deionized water is added until completely dissolved.0.1mL NH is added3·H2O and 0.1mL MPTMS, stirring at normal temperature
24h.The solution being stirred is transferred in the bag filter that molecular cut off is 14000, and replaces primary dialysis every 4~6h
Water dialyses 48h or more the time, obtains C6@To gained C6@Middle addition 60mg mPEG-SH
(M.W.=10000) and 2mg I2, react and obtain C6@for 24 hoursIt is molten that addition MES, NaCl are configured to MES buffering
Liquid adjusts pH to 5.4 or so with NaOH, is added 0.01mmol EDCI/NHS-Sulfo and 10mg PEI (M.W.=600), stirs
Mix reaction for 24 hours, dialysis for 24 hours, obtains final C6@It loads fluorescent dye coumarin 6 (C6) and is used as fluorescence
Marker.
Fig. 9 shows the C6@of synthesisThe cell incubation different time after 20 μM of GSH are pre-processed 2 hours
Cell fluorescence intensity variation.With it is pretreated without GSHIt compares, the pretreated cells show of GSH goes out more
Strong fluorescence illustrates the more nano particles of cell endocytic, it was demonstrated that the interior of cell can be improved in first order redox response
Gulp down effect.
Embodiment 5
By 10mg PCL90-b-PAA175mL N,N-dimethylformamide (DMF) is dissolved in 6mg hydroxycamptothecin (HCPT)
In, 40mL deionized water is added until completely dissolved.0.1mL NH is added3·H2O and 0.1mL MPTMS, stirring at normal temperature is for 24 hours.It will
The solution being stirred is transferred in the bag filter that molecular cut off is 14000, and replaces a water-dialyzing, dialysis every 4~6h
48h or more the time obtains HCPT@To gained HCPT@Middle addition 60mg mPEG-SH (M.W.
=10000) and 2mg I2, react and obtain HCPT@for 24 hoursMES, NaCl is added and is configured to MES buffer solution, uses
NaOH adjusts pH to 5.4 or so, is added 0.01mmol EDCI/NHS-Sulfo and 10mg PEI (M.W.=600), is stirred to react
For 24 hours, dialysis for 24 hours, obtains final HCPT@Its load has hydroxycamptothecin (HCPT).
Figure 10 is final HCPT@To Hepatocellular carcinoma cell line and to l cell NIH-
The cytotoxicity figure of 3T3.The result shows that gained nano material is apparently higher than the cell to normal cell to the toxicity of tumour cell
Toxicity shows the selective killing to tumour cell (this is second level redox response).
Above-described, only presently preferred embodiments of the present invention, the range being not intended to limit the invention, of the invention is upper
Stating embodiment can also make a variety of changes.Made by i.e. all claims applied according to the present invention and description
Simply, equivalent changes and modifications fall within the claims of the invention patent.The not detailed description of the present invention is
Routine techniques content.
Claims (10)
1. a kind of preparation method of Nano medication, which comprises the steps of:
S1, by amphipathic nature block polymer and dewatering medicament that hydrophilic segment contains carboxyl by being self-assembly of medicament-carried nano glue
Beam, wherein dewatering medicament is wrapped in the inside of micella；
S2, medicament-carried nano micelle and the silane coupling agent containing sulfydryl or disulfide bond react to obtain disulfide bond doping, sulfydryl and
First organic silicon nano hydridization micella of carboxyl difunctionalization, wherein the silane coupling agent containing sulfydryl or disulfide bond enters glue
Simultaneously polycondensation is hydrolyzed using micella as template to deposit the organic oxidation silicon layer of disulfide bond doping in the inside of beam；
S3, the first organic silicon nano hydridization micella by oxidation reaction obtain polyethylene glycol and carboxyl difunctionalization it is second organic
Silicon nano hybridization micella, wherein the sulfydryl and polyethylene glycol of the first organic silicon nano hydridization micellar surface are carried out by disulfide bond
It is bonded；
S4, the second organic silicon nano hydridization micella react to obtain receiving for polyethylene glycol and polyethyleneimine difunctionalization by amide
Rice drug, wherein the carboxyl of the second organic silicon nano hydridization micellar surface is carried out with polyethyleneimine by amido bond bonded.
2. preparation method according to claim 1, which is characterized in that in the step S1, block copolymer with it is hydrophobic
Drug is dissolved in organic solvent, and deionized water is added, forms the aqueous solution of medicament-carried nano micelle.
3. preparation method according to claim 2, which is characterized in that block copolymer is polycaprolactone-block- poly- third
Olefin(e) acid.
4. preparation method according to claim 1, which is characterized in that in the step S2, medicament-carried nano micelle is weak
Under the conditions of alkali and silane coupling agent reacts to obtain the first organic silicon nano hydridization micella.
5. the preparation method according to claim 4, which is characterized in that silane coupling agent is 3- mercaptopropyi trimethoxy silicon
Alkane.
6. preparation method according to claim 1, which is characterized in that in the step S3, the first organic silicon nano is miscellaneous
Change micella and mercapto-functionalized polyethylene glycol and the second organic silicon nano hydridization micella is obtained by oxidation reaction.
7. preparation method according to claim 1, which is characterized in that in the step S4, the second organic silicon nano is miscellaneous
Change micella and polyethyleneimine amine amide reacts to obtain Nano medication.
8. preparation method according to claim 7, which is characterized in that the aqueous solution of the second organic silicon nano hydridization micella
Middle addition polyethyleneimine, carbodiimides and N- hydroxy thiosuccinimide, react to obtain Nano medication by amide
Aqueous solution.
9. a kind of Nano medication that the preparation method according to any one of the claims 1-8 obtains.
10. a kind of application of Nano medication according to claim 9, which is characterized in that the bonded poly- second of the Nano medication
The disulfide bond of glycol is opened by the glutathione of the first concentration, and the disulfide bond of the organic oxidation silicon layer of the Nano medication is dense by second
The glutathione of degree is opened, and the first concentration is less than the second concentration.
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN115227673A (en) * | 2022-07-29 | 2022-10-25 | 淮阴工学院 | Nano-carrier with size regulation and control function and preparation method and application thereof |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103735533A (en) * | 2013-12-20 | 2014-04-23 | 中国科学院上海硅酸盐研究所 | Organic and inorganic compound nano-capsule agent and preparation method thereof |
| CN108126211A (en) * | 2017-12-19 | 2018-06-08 | 华东理工大学 | A kind of preparation method of nano hybridization particle and thus obtained nano hybridization particle and Nano medication |
| CN108309937A (en) * | 2018-04-12 | 2018-07-24 | 河南师范大学 | A kind of preparation method for containing the reduction response type nano material of antitumor drug |
-
2019
- 2019-03-14 CN CN201910194169.8A patent/CN109718382A/en active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103735533A (en) * | 2013-12-20 | 2014-04-23 | 中国科学院上海硅酸盐研究所 | Organic and inorganic compound nano-capsule agent and preparation method thereof |
| CN108126211A (en) * | 2017-12-19 | 2018-06-08 | 华东理工大学 | A kind of preparation method of nano hybridization particle and thus obtained nano hybridization particle and Nano medication |
| CN108309937A (en) * | 2018-04-12 | 2018-07-24 | 河南师范大学 | A kind of preparation method for containing the reduction response type nano material of antitumor drug |
Non-Patent Citations (1)
| Title |
|---|
| JIA, XIAOBO ET AL.: "Gradient Redox-Responsive and Two-Stage Rocket-Mimetic Drug", 《NANO LETTERS》 * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN115227673A (en) * | 2022-07-29 | 2022-10-25 | 淮阴工学院 | Nano-carrier with size regulation and control function and preparation method and application thereof |
| CN115227673B (en) * | 2022-07-29 | 2023-07-21 | 淮阴工学院 | Nano-carrier with size regulation and control function and preparation method and application thereof |
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