CN208814949U - A kind of up-conversion luminescence nano-carrier with Bone targeting - Google Patents
A kind of up-conversion luminescence nano-carrier with Bone targeting Download PDFInfo
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Abstract
The utility model provides a kind of up-conversion luminescence nano-carrier with Bone targeting, it is characterised in that: including the inner nuclear layer that shines, at least one layer of protective layer and at least one layer of drug-loaded layer；The outside for being set to inner nuclear layer of protective layer package；The outside for being set to protective layer of drug-loaded layer package；Wherein, a plurality of hydrophilic-structures are modified on the outer surface of drug-loaded layer；Plural channel is equipped in drug-loaded layer；Channel penetrates through drug-loaded layer；The one end in channel is in contact with protective layer；The outer surface of the other end perforation drug-loaded layer in channel, forms plurality of through holes on the outer surface of drug-loaded layer.Macromolecule carrier can be wrapped up UCNP and adsorb a certain amount of E2, to improve the hydrophily of drug, and can reach the controlled-release function of drug by the nano-carrier；Simultaneously also using the special imaging performance of UCNP as bioluminescence marker material, have the function that intracellular tracer.
Description
Technical field
The utility model relates to field of nanometer material technology, and in particular, to a kind of up-conversion luminescence with Bone targeting is received
Meter Zai Ti.
Background technique
Osteoporosis (osteoporosis, OP) is a kind of common bone metabolism venereal disease, because increasing senile fracture
Danger and to society, family causes great harm.In the forming process of bone, osteoblast and osteoclast are bon e formations
Two kinds of main cells of normal bone amount are maintained in the process, the bon e formation and Osteoclasts mediate that osteoblast mediates under normal circumstances
Bone resorption maintain certain quantity and mutually restrict, be in dynamic equilibrium.If this dynamic equilibrium gets muddled or simultaneously
Anomalous variation with endocrine system or vitamine concentration, may interfere with osteoblast and osteoclast, influence the shape of bone
At the absorption with bone, metabolic bone disease is eventually led to, and causes osteoporosis.
The relatively conventional essential osteoporosis of Postmenopausal Osteoporosis occurs after postmenopausal women in 5-10, with
Estrogen level reduces related.Estrogen can inhibit the bone resorption of osteoclast in vivo and in vitro, promote osteoblast
The formation of Proliferation, Differentiation and bone.Some researches show that, 17 beta estradiols (17 β-Estradiol, E2), a kind of estrogens chemical combination
Object can inhibit the femur of Bilateral oophorectomy rat and the bone resorption of shin bone；And promote the proliferation of osteoblast and break up into
And promoting bone growing.Therefore, controversies in hormone replacement in the elderly plays an important role in terms of preventing and treating osteoporosis.It can alleviate
Perimenopausal symptom, including hectic fever, flush, sweating prevent the quick loss of perimenopause bone amount, improve bone density and reduce bone
Roll over the risk occurred.However there are following clinical side effects for long-term use estrogen: endometrial bleeding and hyperplasia can be caused,
Even result in the canceration of inner membrance；Taking estrogen for a long time, there are also increase breast cancer and the slight risk for increasing thrombus.In addition, grinding
Study carefully and shows that the increase of cardiovascular disease and incidence rate of myocardial infarction is also related to hormone therapy is used for a long time.Oral estrogen class medicine
Object is the current most common administration mode, but most of by gastrointestinal tract and liver metabolism, and liver sausage clearance rate is high, absorptivity is low,
Drug plasma concentration fluctuation is larger, does not meet physiological law, and in order to reach therapeutic effect, pair is made while increasing hormone dosage
With can also correspondingly increase.Adverse reaction existing for estrogen prolonged application and bioavilability reduce, hinder its use it is wide
General property, therefore estrogen bioavilability how is improved, and reduce the target that its side effect is estrogen drugs research.
In recent years, nanometer medicine-carried system (nanoparticles, NP) has at bio-imaging, medical diagnosis on disease and treatment aspect
Be widely applied；The bio-diversity for how improving nanometer medicine-carried system simultaneously is also widely studied.Nanometer medicine-carried system
Not only there is drug targeting effect, the bioactivity of hydrophobic drug can also be maintained, reduce the toxic side effect of drug.Due to receiving
The hydrophobicity of rice grain itself, " surface modification is theoretical " are developed well, i.e., are repaired on its surface by further chemistry
It adorns to improve the bio distribution and pharmacokinetics of nano particle.Polyethylene glycol (polyethylene glycol, PEG) is ratio
More common surface ligand.Nano particle can extend its partly declining in blood circulation by polyethylene glycol after surface modification
Phase, what the steric repulsion that the performance of this effect mainly increases particle by improving the opsonic action of fibroin was realized.
In addition, the modification of passivated surface can also reduce polymerizeing for nano particle and non-specific cell and tissue.When through polyethylene glycol
It can express good marrow distribution when the partial size of the nano particle of surface modification is less than 150 nanometers.The report of Moghimi etc. is aobvious
Show that the partial size of nano particle is smaller, is more easily accessible bone tissue；On the contrary, the partial size the big, can be swallowed by liver and spleen.Therefore, through poly-
The nano particle of ethylene glycol surface modification can be used as effective nanometer medicine-carried system and can be targeted in bone tissue.
But this kind of nanometer medicine-carried system mostly lacks signal label, causing can not be real in biological effect research process
When track nanometer medicine-carried system bio distribution, metabolic process etc..Therefore, it is necessary to research and develop at the same have the function of bio-imaging and
The nanometer medicine-carried system of new generation of medication effect, with the deep metabolism for understanding nanometer medicine-carried system in histocyte
Journey.
Utility model content
The utility model is intended to overcome drawbacks described above, provides one kind for hydrophobic drug, can be improved its load and control
Release action processed, and the nano-medicament carrier with Bone targeting.
The utility model provides a kind of up-conversion luminescence nano-carrier with Bone targeting, it is characterised in that: including
Shine inner nuclear layer, at least one layer of protective layer and at least one layer of drug-loaded layer；The multilayered structure can be manufactured by thermosoling and be obtained；
The outside for being set to inner nuclear layer of above-mentioned protective layer package；
The outside for being set to protective layer of above-mentioned drug-loaded layer package；
Wherein, a plurality of hydrophilic-structures are modified on the outer surface of above-mentioned drug-loaded layer；The quantity of the hydrophilic-structure is according to receiving
The partial size of rice material and what is used set.
Plural channel is equipped in above-mentioned drug-loaded layer；The quantity in the channel is according to the particle size of nano material and uses
It is set.
Above-mentioned channel penetrates through drug-loaded layer；
The one end in above-mentioned channel is in contact with protective layer；
The outer surface of the other end perforation drug-loaded layer in above-mentioned channel, forms plurality of through holes on the outer surface of drug-loaded layer.
Further, a kind of up-conversion luminescence nano-carrier with Bone targeting provided by the utility model, also has
Such design feature: i.e., the thickness ratio of above-mentioned inner nuclear layer, protective layer and drug-loaded layer be 1:0.1-1:0.5-2.5.
Further, a kind of up-conversion luminescence nano-carrier with Bone targeting provided by the utility model, also has
Such design feature: i.e., above-mentioned channel is uniformly distributed on drug-loaded layer in radial pattern.
Further, a kind of up-conversion luminescence nano-carrier with Bone targeting provided by the utility model, also has
Such design feature: i.e., in above-mentioned channel being equipped with, have the characteristics that porosity characteristic absorption, to drug have load and controlled release
The structure or material of function.Such as: estrogens compounds.
Further, a kind of up-conversion luminescence nano-carrier with Bone targeting provided by the utility model, also has
Such design feature: i.e., 17-β-estradiol molecule is equipped in above-mentioned channel.
Further, a kind of up-conversion luminescence nano-carrier with Bone targeting provided by the utility model, also has
Such design feature: i.e., the material of above-mentioned inner nuclear layer be the nano material containing rare earth.
Further, a kind of up-conversion luminescence nano-carrier with Bone targeting provided by the utility model, also has
Such design feature: i.e., the material of above-mentioned protective layer be fluorine-containing rare-earth salts.
Further, a kind of up-conversion luminescence nano-carrier with Bone targeting provided by the utility model, also has
Such design feature: i.e., above-mentioned inner nuclear layer be NaLuF4: Yb, Tm nano material；
Above-mentioned protective layer is NaLuF4。
Further, a kind of up-conversion luminescence nano-carrier with Bone targeting provided by the utility model, also has
Such design feature: i.e., above-mentioned drug-loaded layer be amphiphilic polymer Kong Jie's silica.
Further, a kind of up-conversion luminescence nano-carrier with Bone targeting provided by the utility model, also has
Such design feature: i.e., that the material of above-mentioned hydrophilic-structure is selected from EDTA, ionic surfactant, non-ionic surface is living
One or more of property agent.
The effect and effect of the utility model
The utility model provides a kind of nano-carrier, which is made of inner nuclear layer, protective layer and drug-loaded layer, should
Inner nuclear layer has bioluminescence performance, after patient's use, can realize the effect tracked with medicine by medical imaging means.Together
When, the carrier structure of the utility model is special, there is multilayered structure, and the channel of multiple radial patterns is additionally provided on drug-loaded layer,
The effect of medicament slow release and controlled release can be preferably realized by the configuration of this structure.In addition, passing through the hydrophilic modification on surface
The hydrophilicity of hydrophobic drug can also be improved.
In the preferred embodiment of the utility model, applies solvent-thermal method and successively prepare NaLuF4: Yb, Tm and NaLuF4:Yb,
Tm@NaLuF4(UCNP) nano material.Later, amphiphilic polymer Kong Jie silica (MSN) wraps up rare earth upconversion nano
Brilliant (UCNP), and the rare earth up-conversion luminescence nanomaterial for obtaining to be well dispersed in water modified with EDTA, EDTA-
UCNP@MSN.Finally, adsorbing 17 beta estradiol molecules using its porosity characteristic, released with reaching load and the control of hydrophobic drug
The effect of putting.The nano-carrier, using the design feature of above-mentioned each material, the nano material constructed can be by macromolecule carrier
Package UCNP simultaneously adsorbs a certain amount of E2, to improve the hydrophily of drug, and can reach the controlled-release function of drug；Simultaneously also
Using the special imaging performance of UCNP as bioluminescence marker material, have the function that intracellular tracer.
Detailed description of the invention
The schematic diagram of the section structure of attached drawing 1, the up-conversion luminescence nano-carrier provided in this embodiment with Bone targeting；
The manufacturing process schematic diagram of attached drawing 2, the up-conversion luminescence nano-carrier provided in this embodiment with Bone targeting；
The application schematic diagram of attached drawing 3, the up-conversion luminescence nano-carrier provided in this embodiment with Bone targeting.
Attached drawing 4, using mtt assay detection EDTA-UCNP@MSN-E2 load various concentration estrogen when, it is thin to MC3T3-E1
The toxicity and proliferative conditions figure of born of the same parents.
Attached drawing 5, ALP quantitative result figure.
Specific embodiment
As shown in Figure 1, a kind of up-conversion luminescence nano-carrier with Bone targeting is present embodiments provided, in shining
Stratum nucleare 100, protective layer 200 and drug-loaded layer 300 form；
Wherein, the material of inner nuclear layer NaLuF4:Yb, Tm are set to the center of nano-carrier；
Protective layer 200 is NaLuF4Material, the outside for being set to inner nuclear layer 100 of package；
Drug-loaded layer 300 is MSN material, the outside for being set to protective layer 200 of package；
Several EDTA water wetted materials 320 are modified on the outer surface of the drug-loaded layer 300；
Several are equipped in the drug-loaded layer 300, the channel 310 being radially arranged；
The channel 310 penetrates through the thickness of entire drug-loaded layer 300, and one end is in contact with protective layer 200, and other end perforation is straight
Up to the outer surface of drug-loaded layer 300, several through-holes are formed on the outer surface of drug-loaded layer 300.
Be equipped in every channel 310, have the characteristics that porosity characteristic absorption, there is load and control-release function to drug
Estrogens particle 330 is several, and in the present embodiment, which is 17- beta estradiol molecule.
As shown in Fig. 2, present embodiments providing a kind of preparation of up-conversion luminescence nano-carrier with Bone targeting
Journey is as follows.
One, the reagent mainly selected are as follows:
Rare earth oxide (Lu2O3,Yb2O3,Tm2O3) it is purchased from Beijing Lan Su Co., Ltd；DSPE-PEG-NH2It is purchased from
The large biological Co., Ltd of Shang Hai Peng；17-β-estradiol, oleic acid (90%), octadecylene (90%), tetraethoxysilane, (3- amino
Propyl) triethoxysilane, ethylenediamine tetra-acetic acid dianhydride be purchased from Sigma-Aldrich company；Ammonium fluoride, concentrated hydrochloric acid, hydrogen-oxygen
Change sodium, cetyl trimethylammonium bromide, triethylamine, hexamethylene, dehydrated alcohol, chloroform, anhydrous dimethyl base formyl, diformazan
Base sulfoxide is purchased from Chinese medicines group chemical reagents corporation.Rare earth-iron-boron (LuCl3,YbCl3,TmCl3) by rare earth oxide
Middle addition dissolving with hydrochloric acid is simultaneously evaporated obtained.
Two, the up-conversion luminescence nano-carrier with Bone targeting, E2-UCNP@MSN-EDTA materials synthesis route are as follows
It is shown:
Step 1: NaLuF4: the synthesis of Yb, Tm nano material: by the LuCl of 0.79mmol3, the YbCl of 0.20mmol3With
The TmCl of 0.01mmol3It is mixed with the octadecylene of 6ml oleic acid and 15ml, mixed system is heated to 150 under continuous stirring
Degree Celsius and maintain 30 minutes, until system transition be transparent solution.Solution is cooled to 60 degrees Celsius later, it is lasting to stir
Lower addition 10ml contains the methanol solution of 0.1g sodium hydroxide and 0.148 g ammonium fluoride, is heated to 100 degrees Celsius of open volatilization first
After alcohol 30 minutes, system is heated to 300 degrees Celsius and is reacted one hour.After system is cooled to room temperature, 10ml ethyl alcohol pair is added
The NaLuF of synthesis4: Yb, Tm nano particle are precipitated, centrifuge separation retain precipitating solid, and using 10ml hexamethylene with
The mixed solution washing nano material of 10ml ethyl alcohol is three times.Last nano material will be dispersed in stand-by in 5ml hexamethylene.
Step 2: NaLuF4:Yb,Tm@NaLuF4(UCNP) synthesis of nano material: by 1mmol LuCl3With 6ml oleic acid
And the octadecylene mixing of 15ml, mixed system is heated to 150 degrees Celsius under continuous stirring and is maintained 30 minutes, Zhi Daoti
System is changed into transparent solution.Solution is cooled to 60 degrees Celsius later, adds NaLuF4: the cyclohexane solution of Yb, Tm are held
Continuous stirring is lower to carry out 20 minutes removing hexamethylenes of vacuumize process.Persistently be added with stirring 10ml contain 0.1g sodium hydroxide and
System is heated to 300 and taken the photograph by the methanol solution of 0.148g ammonium fluoride after being heated to 100 degrees Celsius of open volatilizations methanol 30 minutes
Family name's degree reacts one hour.After system is cooled to room temperature, 10ml ethyl alcohol is added to the NaLuF of synthesis4:Yb,Tm@NaLuF4Nanometer
Particle is precipitated, and centrifuge separation retains the solid of precipitating, and is washed using the mixed solution of 10 ml hexamethylenes and 10ml ethyl alcohol
Nano material is three times.Last nano material will be dispersed in stand-by in 10ml hexamethylene.
Step 3: UCNP@MSN-NH2Synthesis: weigh 0.1g cetyl trimethylammonium bromide (CTAB) and be dissolved in
In 20mL water, the NaLuF of above-mentioned synthesis is taken4:Yb,Er@NaLuF4The cyclohexane solution 0.5ml of material is diluted to 2ml, then will
It is added dropwise in the solution of CTAB, forms the lotion of white under stiring, is stirred overnight at room temperature later.Solution becomes within second day
For clarification, by the clear solution of 20ml and 50ml water, the sodium hydroxide solution (2mol/L) of 10ml ethyl alcohol and 150ul are mixed,
After being kept for 30 minutes after being heated to 70 degrees Celsius in oil bath, 180ul tetraethoxysilane (TEOS) and 20ul is added dropwise
(3- aminopropyl) triethoxysilane (APTES) mixed solution.After being stirred to react 2 hours, solution is cooled to room temperature, is gone forward side by side
Row centrifuge separation.The solid that centrifugation is obtained three times, obtains UCNP@MSN-NH using 20ml ethanol washing2Nano material.It takes
0.6g ammonium nitrate is dissolved in 50ml ethyl alcohol, and addition synthesizes obtained UCNP@MSN-NH before2Material, in 60 degrees Celsius of oil
Bath lower heating reaction 2 hours, removes remaining CTAB template in mesopore orbit.
Step 4: the synthesis of UCNP@MSN-EDTA: by the UCNP@MSN-NH of 20mg2Material is scattered in the anhydrous of 10ml
In dimethylformamide, 80 degrees Celsius are heated to after the ethylenediamine tetra-acetic acid dianhydride of 100mg and the triethylamine of 50ul are added later
It is kept for 30 minutes, then cool to room temperature and continues stirring 48 hours.System is centrifugated later, the solid of precipitating is used
Ethanol washing is three times.Obtain UCNP@MSN-EDTA material.
Step 5: the synthesis of E2-UCNP@MSN-EDTA: taking UCNP@MSN-EDTA material synthesized by 20mg that 20ml is added
In acetone, it is added 5.6mg 17-β-estradiol (E2), dissolution is uniformly mixed.Acetone is removed using rotary evaporation, is obtained
E2-UCNP@MSN-EDTA material.
The effect and effect of the present embodiment:
The application method and effect for present embodiments providing a kind of up-conversion luminescence nano-carrier with Bone targeting are such as
Shown in Fig. 3.
As shown in figure 4, to MC3T3- when loading various concentration estrogen using mtt assay detection EDTA-UCNP@MSN-E2
The toxicity and proliferative conditions of E1 cell, as the result is shown after dosing for 24 hours, 72h and 7d, load the EDTA- of various concentration estrogen
UCNP@MSN-E2 stablizes proliferation, and significant difference is had no between each group, prompts EDTA-UCNP@MSN-E2 to cytotoxic, also without
The effect of stimulating proliferation.
Alkaline phosphatase (ALP) is a kind of protein closely related with the formation of minerals, and the matrix of osteoblast is small
Bubble release alkaline phosphatase is deposited on collagen under the action of intracellular calcium ion, promotes the calcification of osteoblast to intracellular, because
This, the height of alkaline phosphatase activities is the important indicator for determining cell function and differentiation in osteoblast, and measure at
The whether successful important indicator of self-bone grafting.As shown in figure 5, ALP quantitative result shows EDTA-UCNP@MSN-E2 in 7d, 14d 2
ALP activity can be improved in a time point, shows the effect similar with independent E2, ALP chemical staining result and qualitative detection
As a result consistent, it was demonstrated that EDTA-UCNP@MSN-E2 has the function of promoting osteoblast differentiation.
Calcium scoring is generated in extracellular matrix in conjunction with calcium salt by the collagen of osteoblast secretion, is that identification is thin
Born of the same parents' bone is to the important symbol of differentiation, the results show that cultivating 21d, EDTA-UCNP@MSN-E2 is remarkably improved Mineral nodules
The Mineral nodules number of MC3T3-E1 cell.
In addition, further inquiring into EDTA-UCNP@MSN-E2 nanometer medicine-carried system in life on the basis tested in vitro
Whether there is Bone targeting in object, therefore the biological safety of EDTA-UCNP@MSN-E2 nanometer medicine-carried system is ground
Study carefully.
A. the bone affinity of EDTA-UCNP@MSN-E2 is studied, is imaged using mouse living body and external UCL, utilized
The UCNP exclusive characteristics of luminescence puts to death mouse after 6 hours after a material is injected, isolates important bone and observes its letter that shines
Number intensity, we can be clearly observed that upper limbs on double-side, leg bone, breastbone, vertebral bone and rib cage of mouse etc. have very
Strong upconverted signal illustrates that EDTA-UCNP@MSN-E2 has close bone effect in vivo；Inductively coupled plasma body is former
It is had detected to sub- emission spectrum (ICP-AES) standard measure in the distribution percentage of bone, as a result also demonstrates that material has bone
Targeting.The luminous signals such as uterus, ovary are not strong simultaneously, show EDTA-UCNP MSN-E2 to internal organs such as uterus, ovaries
Affinity is not high.
B. nano material is studied to the prevention effect of rats with osteoporosis: grouping, sham-operation group (SHAM), bilateral ovaries
Cut off (OVX) group, OVX+ estrogen group, OVX+EDTA-UCNP@MSN-E2 group.It is subcutaneous that SHAM group and OVX group give physiological saline
Injection, remaining each group gives the drug of corresponding dosage or Nano medication subcutaneous injection, successive administration put to death animal after 12 weeks, take blood
Clearly, bone and viscera tissue carry out following detection.(1) estrogen and Bone markers in chemiluminescence determination serum, it is female
Hormonal readiness is in normal or higher level, OVX group and OVX+EDTA-UCNP@MSN- in SHAM group and OVX+ estrogen group
E2 group is in low-level, it was demonstrated that the success of osteoporosis model.OCN is in OVX+ estrogen group, OVX+ EDTA-UCNP@MSN-E2
Group is in high level, and then content is lower in serum by CTX.(2) Micro-CT rebuilds lumbar vertebra tissue three-dimensional, OVX+ estrogen
Group, OVX+EDTA-UCNP@MSN-E2 group bone density ratio OVX group are high.(3) shin bone row H&E dyeing, Masson-Goldner
Compared with OVX group, OVX+ estrogen group, OVX+EDTA-UCNP@MSN-E2 group bone trabecula are thick for display after Trichrome dyeing
Strong, gap reduces, structure is more complete.(4) it draws materials to viscera tissues such as heart, liver, spleen, lung, kidney and uterus, row H&E dyeing, group
It is unobvious to knit pathologic structure variation, to illustrate the low bio-toxicity and high-biocompatibility of nanometer medicine-carried system.
Claims (8)
1. a kind of up-conversion luminescence nano-carrier with Bone targeting, including the inner nuclear layer that shines, at least one layer of protective layer and extremely
Few one layer of drug-loaded layer, the drug-loaded layer are amphiphilic polymer Kong Jie's silica, are modified with a plurality of EDTA on outer surface,
It is characterized by:
The outside for being set to inner nuclear layer of the protective layer package；
The outside for being set to protective layer of the drug-loaded layer package；
Wherein, plural channel is equipped in the drug-loaded layer；
The channel penetrates through drug-loaded layer；
The one end in the channel is in contact with protective layer；
The outer surface of the other end perforation drug-loaded layer in the channel, forms plurality of through holes on the outer surface of drug-loaded layer.
2. a kind of up-conversion luminescence nano-carrier with Bone targeting as described in claim 1, it is characterised in that: in described
The thickness ratio of stratum nucleare, protective layer and drug-loaded layer is 1:0.1-1:0.5-2.5.
3. a kind of up-conversion luminescence nano-carrier with Bone targeting as described in claim 1, it is characterised in that: described logical
Road is uniformly distributed on drug-loaded layer in radial pattern.
4. a kind of up-conversion luminescence nano-carrier with Bone targeting as described in claim 1, it is characterised in that: described logical
It is equipped in road, has the characteristics that structure or material that porosity characteristic is adsorbed, that there is load and control-release function to drug.
5. a kind of up-conversion luminescence nano-carrier with Bone targeting as claimed in claim 4, it is characterised in that: described logical
17-β-estradiol molecule is equipped in road.
6. a kind of up-conversion luminescence nano-carrier with Bone targeting as described in claim 1, it is characterised in that: in described
The material of stratum nucleare is the nano material containing rare earth.
7. a kind of up-conversion luminescence nano-carrier with Bone targeting as described in claim 1, it is characterised in that: the guarantor
The material of sheath is fluorine-containing rare-earth salts.
8. a kind of up-conversion luminescence nano-carrier with Bone targeting as described in claim 1, it is characterised in that: in described
Stratum nucleare is NaLuF4: Yb, Tm nano material；
The protective layer is NaLuF4。
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112220777A (en) * | 2020-10-16 | 2021-01-15 | 北京大学口腔医学院 | Microenvironment response type osteoblast targeted drug-loaded nanoparticle and preparation method and application thereof |
| CN116019932A (en) * | 2023-02-03 | 2023-04-28 | 山东大学 | Preparation and application of near-infrared photosensitive miR-21 up-conversion nano delivery particles |
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2017
- 2017-12-20 CN CN201721794446.1U patent/CN208814949U/en active Active
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112220777A (en) * | 2020-10-16 | 2021-01-15 | 北京大学口腔医学院 | Microenvironment response type osteoblast targeted drug-loaded nanoparticle and preparation method and application thereof |
| CN112220777B (en) * | 2020-10-16 | 2022-04-12 | 北京大学口腔医学院 | Microenvironment response type osteoblast targeted drug-loaded nanoparticle and preparation method and application thereof |
| CN116019932A (en) * | 2023-02-03 | 2023-04-28 | 山东大学 | Preparation and application of near-infrared photosensitive miR-21 up-conversion nano delivery particles |
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