CN105997881A - Tumor cell targeting mesoporous silicon nanometer assembly and preparation method for same - Google Patents
Tumor cell targeting mesoporous silicon nanometer assembly and preparation method for same Download PDFInfo
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Abstract
The invention discloses a tumor cell targeting mesoporous silicon nanometer assembly and a preparation method for the same. The preparation method specifically comprises the following steps: (1) performing synthesis to obtain a crude product at 75 to 85 DEG C under an alkaline condition by taking a surfactant cetyl trimethyl ammonium bromide as a template and taking tetraethyl orthosilicate as a silicon source, and performing post-treatment to remove the surfactant to obtain mesoporous silicon; (2) mixing the mesoporous silicon and a drug in ethanol to obtain drug-loaded mesoporous silicon; (3) dispersing the drug-loaded mesoporous silicon with a phosphate buffer solution PBS, adding the solution into a liposome membrane, and performing hydration and homogenization to obtain liposome-wrapped mesoporous silicon nanoparticles; (4) reacting the liposome-wrapped mesoporous silicon nanoparticles with HA to obtain a target material. The preparation method is simple; by the obtained mesoporous silicon nanometer assembly, the drug uptake of tumor cells can be enhanced from targeting and drug diffusion prevention to achieve the effect of treating tumors, and the mesoporous silicon nanometer assembly has obvious advantages in tumor treatment.
Description
Technical field
The invention belongs to technical field of medicine, be specifically related to a kind of nanometer with tumor cell targeting and assemble
Body and preparation method thereof.
Background technology
In the last few years, malignant tumor became the principal disease threatening human life healthy, and M & M is in recent years
In the trend risen year by year.Therefore, during the research and development of antitumor drug become the weight of national governments, research institution and drugmaker
Weight, also gives highest attention to antitumor drug research.At present, although the mode for the treatment of tumor and means are numerous, but
It is that chemotherapy is still that the Main Means treating tumor.But this method but also exists the problem of many, such as side effect is big,
Poor selectivity, drug resistance are strong, and the more important thing is in the embolic chemotherapy of routine, and chemotherapeutics is distributed in whole body, but swollen
Tumor position is but difficult to reach to effectively treat concentration, and then causes the generation of the toxic and side effects of many, carries to patient and family members thereof
Carry out many miseries.For seeking a kind of safe efficient, dosage form of targeting, researcher permeability based on tumor microenvironment is strong,
Lack the features such as lymphsystem, slightly acidic environment, some specific proteins of high expressed, utilize the nanotechnology maked rapid progress,
Want to develop more reliable and more stable nano-carrier to treat tumor.
A kind of nano-carrier of inorganic material mesoporous silicon oxide (mesoporous silica nanoparticles, MSNs) conduct,
Himself have excellent attribute, stable in physicochemical property, specific surface area are big, hole and granularity is controlled, modifiability strong and
Good biocompatibility, is a kind of excellent pharmaceutical carrier, is widely used in biomedicine field.But MSNs
Equally exist the uncontrollable release of medicine and arrive the leakage of target prodrug, and then the problem causing side effect.
Summary of the invention
In order to overcome the deficiencies in the prior art, it is an object of the invention to provide a kind of mesoporous silicon with tumor cell targeting
Nanoscale assemblies and preparation method thereof.The nanometer assembly of the present invention is hyaluronic acid decorated lipid-mesoporous silicon nucleocapsid
Nanoscale assemblies, it makes use of the architectural difference between tumor tissues and normal structure, makes nanoparticle arrive by EPR effect
And it is stranded in tumor tissues, and due to the CD44 receptor of tumor cell overexpression, so tumor cell can huge uptake
Hyaluronic acid decorated lipid-mesoporous silicon core-shell nano assembly, and then reach to strengthen drug level in tumor cell, enhancing is controlled
The ability for the treatment of effect.
The present invention provides the preparation method of a kind of nanometer assembly with tumor cell targeting, and concrete steps are such as
Under:
(1) first using surfactant as template, tetraethyl orthosilicate is as silicon source, in the basic conditions, and 75-85 DEG C of temperature
Lower synthesis obtains crude product, then post processing removes surfactant, obtains mesoporous silicon；
(2) mesoporous silicon and medicine are mixed in ethanol, obtain medicine carrying mesoporous silicon；Wherein: described agent selected from doxorubicin,
In paclitaxel or 10-hydroxycamptothecine any one；
(3), after medicine carrying mesoporous silicon being disperseed by phosphate buffered solution PBS, join in liposome membrane, first aquation, more all
Matter, obtains the nanometer grain of liposome；Wherein: described liposome membrane by hydrogenated soy phosphatidyl choline, cholesterol and
DSPE reaction prepares；
(4) by nanometer grain and the hyaluronic acid HA reaction of liposome, obtain that there is tumor cell targeting
Nanometer assembly.
In above-mentioned steps (1), surfactant is cetyl trimethylammonium bromide.
In above-mentioned steps (1), crude product is refluxed in the mixed liquor of ethanol and hydrochloric acid, remove surfactant.
In above-mentioned steps (3), aquation at a temperature of 50-80 DEG C, homogenizing under the conditions of 500-1200Pa.
In above-mentioned steps (4), when preparation has the nanometer assembly of tumor cell targeting, first with EDC and
Hyaluronic acid HA is activated by NHSS.
In the present invention, the mass ratio of mesoporous silicon and medicine is 1:1-10:1；Hyaluronic acid with the mass ratio of liposome membrane is
1:2-1:50；The mass ratio of mesoporous silicon and liposome membrane is at 1:2-1:8.
The present invention also provides for the nanometer assembly with tumor cell targeting that a kind of above-mentioned preparation method obtains.
Preferably, its particle size range is between 80nm-450nm.
The beneficial effects of the present invention is:
The nanometer assembly of the present invention can strengthen tumor cell to medicine from targeting in terms of preventing drug diffusion two
Picked-up, thus reach treat tumor effect, the treatment for tumor has obvious advantage.
The present invention is coated on mesoporous silicon surface with lipid film, it is possible to resolve mesoporous silicon medicine carrying release poor controllability and asking of revealing in advance
Topic, indirectly enhances nanoparticle and arrives the ability of tumor locus；And again with hyaluronic acid as target spot, it is possible to effectively promote
Enter the tumor cell picked-up to drug-carrying nanometer particle, and then strengthen the drug level in tumor cell, advantageously controlling in tumor
Treat.The nanometer assembly of the above present invention combines the advantage of mesoporous silicon and liposome, is a kind of great potential
New type functional carrier.
Accompanying drawing explanation
The transmission electron microscope picture of Fig. 1: MSNs (A) and LB-MSNs (B).
Fig. 2: pharmaceutical carrier fluorescence imaging result under laser confocal microscope.
The difference that Fig. 3: flow cytometer measures contains drug carrier in HeLa intracellular release situation.
Fig. 4: MTT experiment result.
Detailed description of the invention
The nanoparticle of the tumor cell of the targeting overexpression CD44 receptor that the present invention constructs, its mesoporous silicon has good
Drug loading capacity, liposome can effectively prevent medicine from revealing in advance, and hyaluronic acid can efficient targeting tumor cell.
Embodiment 1
A kind of preparation method of hyaluronic acid decorated lipid mesoporous silicon core-shell nano assembly
(1) preparation of nanometer granule: take the 2mol/L NaOH solution of 3.6mL, joins in 800mL water,
It is heated to 80 DEG C, then the ethanol solution being dissolved with 2.4g cetyl trimethylammonium bromide CTAB is joined 80 DEG C of heat
In water, under conditions of rotating speed 700rpm, react 2h.It is then slowly added into tetraethyl orthosilicate TEOS 8mL, followed by
Continuous reaction 8h.In this reaction system, add isopyknic ethanol, after having flocculent deposit to separate out, filter, will precipitate molten
Solution is at ethanol: in the mixed liquor of hydrochloric acid=9:1,80 DEG C of backflow 8h, just can effectively remove surfactant, be then centrifuged for,
It is dried, obtains the mean diameter nanometer grain (MSNs) at about 85nm.
(2) the mesoporous silicon ethanol dispersion that will prepare, by itself and amycin (DOX) solution therewith of 10mg/mL,
Lucifuge stirring 8h so that it is be fully contacted.It is centrifuged after 8h, rinses repeatedly with PBS, when liquid to be rinsed is without color
Obtain the mesoporous silicon DOX@MSNs of medicine carrying.Collect the buffer and the DOX solution of remnants rinsed, utilize ultraviolet to divide
Light photometer, under conditions of wavelength is 480nm, measures the DOX concentration of residual solution, and then tries to achieve the load of MSNs
Dose.After measured, the drug loading of final MSNs is 11.28mg, and i.e. every 100mg MSNs carries 11.28mg DOX.
(3) 25mg hydrogenated soy phosphatidyl choline, 6.25mg cholesterol and 1.64mg distearoylphosphatidyl second are weighed respectively
Hydramine, is dissolved in 20mL chloroform.30 DEG C of rotations are steamed into film.With the 40mL PBS having dissolved 10mg mesoporous silicon
Aquation lipid film, under the water bath condition of 60 DEG C, uses Rotary Evaporators aquation.Homogenizer is high under conditions of 1000Pa
Pressure homogenizing 5min, must wrap the liposome (LB-MSNs) being loaded with mesoporous silicon.
(4) weigh 26mg hyaluronic acid HA (200-400KDa) and be placed in 10mL distilled water (pH is adjusted to 4.0 in advance)
In, hydrated overnight is allowed to the most swelling and dissolves；Add 12mg 1-ethyl-(3-dimethylaminopropyl) carbodiimide salt
Hydrochlorate (EDC) and 6.8mg N-hydroxy-succinamide (NHSS), with 1mol/L salt acid for adjusting pH to 4.0, in 37
Activate 2h, the HA of activation under DEG C water bath condition and add in liposome turbid liquor with the mass ratio (HA/Lipid) of 10%,
By 0.1M borate buffer solution regulation system pH to 8.6,37 DEG C of reactions are overnight；After reaction terminates, it is centrifuged off reaction
By-product and free HA (12000rpm, 4 DEG C, 30min), deionized water wash 3 times, obtain nanometer and assemble
Body [email protected] the particle diameter of nanoparticle of embodiment 1, PDI and zeta current potential, concrete outcome is shown in Table
1。
Table 1
From upper table it can be seen that prepared nanometer grain MSNs particle diameter is little, size is uniform, with elecrtonegativity；And be somebody's turn to do
Nanoparticle is being wrapped up by lipid bilayer and by after hyaluronic acid decorated, particle diameter increases, and zeta current potential increases, and makes nanoparticle
The most stable.
By the microstructure of the nano-carrier in hom ology embodiment 1, such as Fig. 1 (MSNs (A) and LB-MSNs
(B) transmission electron microscope picture) shown in.MSNs is that class is spherical, has a pore passage structure clearly, uniform particle diameter, compound with regular structure,
The result that size is tested with SAXRD matches, and has bigger specific surface area.And LB-MSNs shape rounding,
It can clearly be seen that it is wrapped with one layer of lipid bilayer at mesoporous silicon, this direct proof has successfully prepared lipid
-mesoporous silicon core-shell nano carrier.
Embodiment 2
A kind of preparation method of hyaluronic acid decorated lipid mesoporous silicon core-shell nano assembly
(1) preparation of nanometer granule, the mesoporous silicon second that will prepare is prepared according to method described in embodiment 1
Alcohol disperses, by itself and amycin (DOX) solution therewith of 15mg/mL, lucifuge stirring 8h so that it is be fully contacted.8h
Rear centrifugal, rinse repeatedly with PBS, when liquid to be rinsed is without color, obtain the mesoporous silicon DOX@MSNs of medicine carrying.Receive
The buffer of collection flushing and the DOX solution of remnants, utilize ultraviolet spectrophotometer, be the condition of 480nm at wavelength
Under, measure the DOX concentration of residual solution, and then try to achieve the drug loading of MSNs.After measured, the medicine carrying of final MSNs
Amount is 12.68mg, and i.e. every 100mg MSNs carries 12.68mg DOX.
(2) 30mg hydrogenated soy phosphatidyl choline, 7.5mg cholesterol and 1.92mg distearoylphosphatidyl ethanol are weighed respectively
Amine, is dissolved in 20mL chloroform.30 DEG C of rotations are steamed into film.With the 40mL PBS water having dissolved 20mg mesoporous silicon
Change lipid film, under the water bath condition of 60 DEG C, use Rotary Evaporators aquation.Homogenizer is high pressure under conditions of 1000Pa
Homogenizing 5min, must wrap the liposome DOX@LB-MSNs being loaded with mesoporous silicon.
(3) weigh 26mg HA (200-400KDa) to be placed in 10mL distilled water (pH is adjusted to 4.0 in advance), water
Close and be overnight allowed to the most swelling and dissolve；Add 12mg EDC and 6.8mg NHSS, with 1mol/L salt acid for adjusting pH extremely
4.0, under 37 DEG C of water bath condition activate 2h, the HA of activation with the mass ratio (HA/Lipid) of 10% add to liposome mix
In suspension, by 0.1M borate buffer solution regulation system pH to 8.6,37 DEG C of reactions are overnight；After reaction terminates, centrifugal
Remove byproduct of reaction and free HA (12000rpm, 4 DEG C, 30min), deionized water wash 3 times, obtain mesoporous silicon
Nanoscale assemblies [email protected] the particle diameter of nanoparticle of embodiment 2, PDI and zeta current potential, specifically
The results are shown in Table 2.
Table 2
Embodiment 3
(1) according to embodiment 1, the mesoporous silicon ethanol dispersion that will prepare, by itself and 10-hydroxycamptothecine solution therewith,
Lucifuge stirring 24h so that it is be fully contacted.It is centrifuged after 8h, rinses with PBS, vacuum drying, load 10-must be wrapped
The MSNs of hydroxy camptothecin, lucifuge room temperature preservation.
(2) 25mg hydrogenated soy phosphatidyl choline, 6.25mg cholesterol and 1.64mg distearoylphosphatidyl second are weighed respectively
Hydramine, is dissolved in 20mL chloroform.30 DEG C of rotations are steamed into film.With the 40mL PBS having dissolved 10mg mesoporous silicon
Aquation lipid film, under the water bath condition of 60 DEG C, uses Rotary Evaporators aquation.Homogenizer is high under conditions of 1000Pa
Pressure homogenizing 5min, must wrap the liposome being loaded with mesoporous silicon.
(3) weigh 26mg HA (600-800KDa) to be placed in 10mL distilled water (pH is adjusted to 4.0 in advance), water
Close and be overnight allowed to the most swelling and dissolve；Add 12mg EDC and 6.8mg NHSS, with 1mol/L salt acid for adjusting pH extremely
4.0, under 37 DEG C of water bath condition activate 2h, the HA of activation with the mass ratio (HA/Lipid) of 10% add to liposome mix
In suspension, by 0.1M borate buffer solution regulation system pH to 8.6,37 DEG C of reactions are overnight；After reaction terminates, centrifugal
Remove byproduct of reaction and free HA (12000rpm, 4 DEG C, 30min), deionized water wash 3 times, obtain mesoporous silicon
Nanoscale assemblies [email protected] the particle diameter of nanoparticle of embodiment 3, PDI and zeta current potential, specifically
The results are shown in Table 3.
Table 3
Embodiment 4
(1) according to embodiment 1, the mesoporous silicon ethanol dispersion that will prepare, by itself and 10-hydroxycamptothecine solution therewith,
Lucifuge stirring 24h so that it is be fully contacted.It is centrifuged after 8h, rinses with PBS, vacuum drying, load 10-must be wrapped
The MSNs of hydroxy camptothecin, lucifuge room temperature preservation.
(2) 30mg hydrogenated soy phosphatidyl choline, 8.4mg cholesterol and 1.96mg distearoylphosphatidyl ethanol are weighed respectively
Amine, is dissolved in 20mL chloroform.30 DEG C of rotations are steamed into film.With the 40mL PBS water having dissolved 15mg mesoporous silicon
Change lipid film, under the water bath condition of 60 DEG C, use Rotary Evaporators aquation.Homogenizer is high pressure under conditions of 1000Pa
Homogenizing 5min, must wrap the liposome being loaded with mesoporous silicon.
(3) weigh 18mg HA (600-800KDa) to be placed in 10mL distilled water (pH is adjusted to 4.0 in advance), water
Close and be overnight allowed to the most swelling and dissolve；Add 12mg EDC and 6.8mg NHSS, with 1mol/L salt acid for adjusting pH extremely
4.0, under 37 DEG C of water bath condition activate 2h, the HA of activation with the mass ratio (HA/Lipid) of 12% add to liposome mix
In suspension, by 0.1M borate buffer solution regulation system pH to 8.6,37 DEG C of reactions are overnight；After reaction terminates, centrifugal
Remove byproduct of reaction and free HA (12000rpm, 4 DEG C, 30min), deionized water wash 3 times, obtain mesoporous silicon
Nanoscale assemblies [email protected] the particle diameter of nanoparticle of embodiment 4, PDI and zeta current potential, specifically
The results are shown in Table 4.
Table 4
Application Example
The application DOX@MSNs solution that medicine carrying concentration is 0.028mg/mL prepared by above-described embodiment 1,
DOX@LB-MSNs solution, DOX@HA-LB-MSNs solution, the DOX solution then preparing 0.028mg/mL is made
For comparison.
One, specificity intracellular picked-up
(1) cellular uptake of hyaluronic acid mediated
The DOX@HA-LB-MSNs and DOX@LB-MSNs of FITC labelling is compared with confocal laser scanning microscope
Picked-up situation when pH 7.4.
By HeLa cell with 5 × 104Individual/hole is inoculated on the glass cover-slip of 12 orifice plates, and every hole adds containing 10% hyclone
DMEM culture medium 1.5mL, be placed in 37 DEG C, 5%CO2Constant incubator is cultivated.Cultivate 8h, be separately added into and contain
Having the DMEM culture medium of MSNs, LB-MSNs and HA-LB-MSNs, the blank culture fluid without nanoparticle is as the moon
Property comparison, in incubator, hatch 5h altogether.Remove culture medium, rinse cell with 4 DEG C of aseptic PBS, with 90% glycerol envelope
Sheet, is placed under Laser Scanning Confocal Microscope observation.
(2) flow cytometer quantitative determination medicine intracellular intake
DOX@HA-LB-MSNs intake of HeLa cell in pH7.4 culture medium is quantitative determined with flow cytometer,
And using DOX solution, DOX@MSNs, DOX@LB-MSNs as comparison.
By HeLa cell with 2 × 104Individual/hole is inoculated in 12 orifice plates, and every hole adds cultivates containing 10% hyclone DMEM
Based 1.5 mL, is placed in 37 DEG C, 5%CO2Constant incubator is cultivated.After cultivating 8h, treat that cell density is 5 × 105Individual/
Kong Shi, is separately added into the DMEM culture medium acetone soln containing different nano-carriers, hatches 6h in culture medium altogether, move
Except culture medium, rinsing cell three times with 4 DEG C of aseptic PBS, trypsinization, 2000rmp is centrifuged 3min, and cell is resuspended in
In 0.5mL PBS, use flow cytomery red fluorescence intensity, draw intracellular fluorescence intensity-time graph.
Pharmaceutical carrier fluorescence imaging result under laser confocal microscope is as in figure 2 it is shown, contained drug adriamycin is red
Fluorescence represents, the fluorescent material FITC green fluorescence that connecting has mesoporous silicon carrier surface to connect represents.Result shows, respectively
Vehicle group fluorescence intensity is followed successively by HA-LB-MSNs, LB-MSNs, MSNs.Can find out clearly from figure, with
MSNs, LB-MSNs group is compared, and HA-LB-MSNs group redness in HeLa cell and green fluorescence intensity are maximum.
This absolutely proved HeLa born of the same parents can effective targeting picked-up HA-LB-MSNs, namely prove that HA-LB-MSNs can be by
Tumor cell absorbs, and is discharged in tumor cell by medicine.
From Fig. 3 (flow cytometer measure difference containing drug carrier in Hela intracellular release situation) it can be seen that from
Turning left in the right side, each drug concentration is followed successively by DOX@HA-LB-MSNs, DOX@LB-MSNs, DOX solution,
DOX@MSNs and blank.It is obvious that DOX@HA-LB-MSNs is maximum in HeLa intracellular release amount
, about 3 times of about DOX solution group, about the twice of [email protected] result and the result of Fig. 2
Confirm mutually, prove HA-LB-MSNs further
Tumor cell intracellular is actively delivered there is obvious facilitation, it is possible to efficient targeting tumor cell transporting drugs enter
Enter tumor cell.
Two, extracorporeal anti-tumor effect
With mtt assay detect DOX@HA-LB-MSNs vitro cytotoxicity, and with DOX solution, DOX@MSNs,
DOX@LB-MSNs is as comparison.
By HeLa cell with 2 × 104Individual/hole or 1 × 104Individual/hole is inoculated in 96 orifice plates, and every hole adds containing 10% tire cattle
Serum DMEM culture medium 0.1mL, is placed in 37 DEG C, 5%CO2Constant incubator is cultivated.After cultivating 24 hours, with
Culture medium dilution medicine, drug level set 6 gradients (with contained DOX as standard, 0,0.25,0.5,1,2,4,
8 μ g/mL), often group sets 3 multiple holes, after cultivating 4h, sucking-off culture fluid, changes to fresh culture, cultivate cell 12,
24、48h.After hatching end, every hole adds freshly prepared MTT solution (5mg/mL) 10 μ L, continues to hatch 4h；
Abandoning supernatant, every hole adds DMSO 100 μ L, puts concussion in 37 DEG C of shaking tables and dissolves purple crystal product, in 490nm
Place's detection absorbs angle value.
From Fig. 4 (MTT experiment result) it can be seen that the suppression of cell viability is imitated by DOX solution with DOX@MSNs
Fruit is the most weak, and the survival rate of cell is always more than 70%, and LB-MSNs takes second place, and tumor cell is pressed down by HA-LB-MSNs
Making of the most obvious, the inhibitory action of cell is reduced to about 30%, and this result and above-mentioned Fig. 2, with the result of Fig. 3
Mutually confirmation, shows that HA-LB-MSNs can be effectively by HeLa cellular uptake, and by drug release in tumor cell,
And then the growth of suppression cell, thus reach antineoplastic target.
In sum, this kind of drug-loading system can be from targeting with strengthen tumor cell in terms of preventing drug diffusion two and take the photograph medicine
Taking, thus reach to treat the effect of tumor, the treatment for tumor has obvious advantage.
Claims (8)
1. the preparation method of a nanometer assembly with tumor cell targeting, it is characterised in that specifically comprise the following steps that
(1) first using surfactant as template, tetraethyl orthosilicate is as silicon source, in the basic conditions, and 75-85 DEG C of temperature
Lower synthesis obtains crude product, then post processing removes surfactant, obtains mesoporous silicon；
(2) mesoporous silicon and medicine are mixed in ethanol, obtain medicine carrying mesoporous silicon；Wherein: described agent selected from doxorubicin,
In paclitaxel or 10-hydroxycamptothecine any one；
(3), after medicine carrying mesoporous silicon being disperseed by phosphate buffered solution PBS, join in liposome membrane, first aquation, more all
Matter, obtains the nanometer grain of liposome；Wherein: described liposome membrane by hydrogenated soy phosphatidyl choline, cholesterol and
DSPE reaction prepares；
(4) by nanometer grain and the hyaluronic acid HA reaction of liposome, obtain that there is tumor cell targeting
Nanometer assembly.
Preparation method the most according to claim 1, it is characterised in that in step (1), surfactant is cetyl
Trimethylammonium bromide.
Preparation method the most according to claim 1, it is characterised in that in step (1), by crude product at ethanol and hydrochloric acid
Mixed liquor refluxes, removes surfactant.
Preparation method the most according to claim 1, it is characterised in that in step (3), aquation at a temperature of 50-80 DEG C,
Homogenizing under the conditions of 500-1200Pa.
Preparation method the most according to claim 1, it is characterised in that in step (4), preparation has tumor cell targeting
During the nanometer assembly of property, first with EDC and NHSS, hyaluronic acid HA is activated.
Preparation method the most according to claim 1, it is characterised in that the mass ratio of mesoporous silicon and medicine is 1:1-10:1；Thoroughly
The acid of bright matter is 1:2-1:50 with the mass ratio of liposome membrane；The mass ratio of mesoporous silicon and liposome membrane is at 1:2-1:8.
7. the nanometer group with tumor cell targeting obtained according to the preparation method one of claim 1-6 Suo Shu
Dress body.
The nanometer assembly with tumor cell targeting the most according to claim 7, it is characterised in that its particle diameter
Scope is between 80nm-450nm.
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| CN107625966A (en) * | 2017-09-10 | 2018-01-26 | 河南工业大学 | A kind of self assembling type lipid mesoporous silicon core shell composite nano pharmaceutical carrier and preparation method thereof |
| CN108186573A (en) * | 2018-02-26 | 2018-06-22 | 广东药科大学 | It is a kind of using lipid encapsulation mesoporous silicon oxide as hydroxycamptothecin Liver targeting preparation of carrier and preparation method thereof |
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| CN107213476A (en) * | 2017-07-12 | 2017-09-29 | 重庆医科大学 | A kind of hyaluronic acid decorated silicon parcel carries medicine phosphatide liquid fluorocarbon nanosphere acoustic contrast agent and preparation method thereof |
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| CN108186573A (en) * | 2018-02-26 | 2018-06-22 | 广东药科大学 | It is a kind of using lipid encapsulation mesoporous silicon oxide as hydroxycamptothecin Liver targeting preparation of carrier and preparation method thereof |
| CN111084759A (en) * | 2020-01-17 | 2020-05-01 | 福建师范大学 | Medicine carrying system for loading anticancer medicine and preparation and application thereof |
| CN111084759B (en) * | 2020-01-17 | 2021-10-08 | 福建师范大学 | Medicine carrying system for loading anticancer medicine and preparation and application thereof |
| CN113546058A (en) * | 2021-07-06 | 2021-10-26 | 吕梁学院 | Nanoparticles for inhibiting TERT (TERT-terminal electron transfer) nucleation, preparation method and application |
| CN115212318A (en) * | 2022-07-04 | 2022-10-21 | 河南工业大学 | Microenvironment response type lipid mesoporous silicon core-shell nano delivery carrier and preparation method and application thereof |
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