CN104784692A - Method for preparing core-shell structure drug carrier with near-infrared light remote response and application thereof - Google Patents
Method for preparing core-shell structure drug carrier with near-infrared light remote response and application thereof Download PDFInfo
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Abstract
The invention discloses a method for preparing a core-shell structure drug carrier with near-infrared light remote response and an application thereof, belongs to the field of biomedical materials, and particularly discloses a method for preparing a core-shell structure drug carrier with near-infrared light remote response and an application thereof. The invention aims at solving the problems of shallow light source penetration depth, high cost and big risk of the current atherosclerosis traditional photodynamics therapy. The method comprises the following steps: firstly synthesizing a core-shell structure nano-particle coated with a photosensitizer, wherein the nano-particle is swallowed by the cell in the cell co-culture process; and radiating the cell by near-infrared light, wherein under the stimulation of the near-infrared light, the nano-particle in the cell is acted with the tissue oxygen to generate a cytotoxic active oxygen molecule singlet oxygen (1O2) so as to kill the cell till apoptosis. The core-shell structure drug carrier with near-infrared light remote response prepared by the invention is taken as a medical carrier for inhibiting and killing the atherosclerosis plaque cell.
Description
Technical field
The invention belongs to biomedical materials field, be specifically related to a kind of preparation method and the application thereof with the nuclear shell structure drug carrier of near infrared light remote response.
Background technology
In recent years, along with the raising of people's living standard, the sickness rate of the cardiovascular and cerebrovascular diseases such as atherosclerosis remains high, and has become and has been only second to the second largest killer that cancer threatens human health.The main Pathologic changes of atherosclerosis is the formation of a large amount of speckle of Ink vessel transfusing, and wherein breaking suddenly of some speckle is the major reason causing the cardiovascular and cerebrovascular disease such as myocardial infarction and apoplexy.How suppressing the formation of speckle and found by early diagnosis and eliminate unstable spot, is the key of Prevention and Curation cardiovascular and cerebrovascular disease.
Main drug application treatment is treated with Ink vessel transfusing mechanical intervention clinically at present.Drug therapy belongs to expectant treatment, can only delay atherosclerotic process, and treatment lacks selectivity, can not carry out emphasis treatment to concrete position.Ink vessel transfusing mechanical intervention is treated, such as endarterectomy, balloon angioplasty and support etc., although really greatly reduce the mortality rate that atherosclerosis causes cardiovascular and cerebrovascular disease, but operation risk is large, costly, postoperative easy generation neointimal hyperplasia or compressibility reconstruct the vascular restenosis caused.For atherosclerosis compared with the treatment of mild case and prevention, still need other method to observe, suppress, eliminate potential pathological changes speckle.
The therapy that optical dynamic therapy destroys pathological tissues as a kind of optical excitation specificity has a wide range of applications in cancer and a lot of disease, and wherein the histoclastic ability of selectivity targeting is applicable to the treatment for atheromatous plaque very much.Its mechanism of action is the photosensitizer that the optical excitation of certain wavelength is Wavelength matched with it, under the existence of tissue oxygen, produces and has Cytotoxic active oxygen species (singlet oxygen) killer cell.In research work in early days, the hemoporphyrin compound as first generation photosensitizer is just used to the exploration carrying out optical dynamic therapy for atheromatous plaque cell.Along with going deep into of research, find that purity is higher successively, the better hemoporphyrin compound of selectivity and derivant thereof.In addition based on intravascular luminescent Manifold technology progress also for optical dynamic therapy unstable spot introduce vascular system provide prerequisite.
Although photodynamic therapy has good effect on treatment atheromatosis, but for traditional photodynamic therapy, due to the problem of light penetration depth in bio-tissue, its application is extremely restricted: on the one hand, the excitation wavelength of most of photosensitizer is all below 700 nanometers, when this wavelength, blood can make significantly to weaken according to the light intensity to targeting plaque cells with organizing existence, causes optical dynamic therapy efficiency significantly to reduce.On the other hand, the position of Mottling formation, probably in systemic comparatively deep location, so need strong penetration capacity light source (being greater than 800 nm near-infrared light) to implement optical dynamic therapy, just can reach satisfied therapeutic effect.
Summary of the invention
The present invention is to solve the problem that existing atherosclerosis tradition photodynamic therapy light source penetration depth is shallow, cost is high and have a big risk, and provides a kind of preparation method and the application thereof with the nuclear shell structure drug carrier of near infrared light remote response.
A kind of preparation method with the nuclear shell structure drug carrier of near infrared light remote response is specifically carried out according to the following steps:
One, by NaYF
4: Yb/Er up-conversion nanoparticles is scattered in cyclohexane extraction, obtains up-conversion nanoparticles core;
Two, in DMF solvent, add dicyclohexylcarbodiimide, chlorin e 6 and 3-aminopropyl triethoxysilane successively, obtain mixed solution, mixed solution is at room temperature left standstill 24h, obtains photosensitizer condensation solution; The quality of described dicyclohexylcarbodiimide and the volume ratio of DMF solvent are 1mg:(1.5 ~ 2) mL; The quality of described chlorin e 6 and the volume ratio of DMF solvent are 1mg:(0.5 ~ 0.8) mL; The volume ratio of described 3-aminopropyl triethoxysilane and DMF solvent is 1:(180 ~ 220);
Three, cetrimonium bromide is joined stirring and dissolving in solvent orange 2 A, then the up-conversion nanoparticles core that step one obtains is added wherein, ultrasonic 30min after stirring 30min, obtain ultrasonic solution, be heat 30min under the condition of 80 DEG C in ultrasonic solution, to add solvent B after ultrasonic solution is transparent in temperature, and be 9 with the pH of sodium hydroxide solution adjustment ultrasonic solution, adopting peristaltic pump in ultrasonic solution, add concentration is after the tetraethoxysilane alcoholic solution of 25%, add the photosensitizer condensation solution that step 2 obtains again, after at room temperature reacting 24h, solid is obtained by centrifugalize, solid is adopted ethanol purge 3 ~ 5 times, then vacuum drying 24h in vacuum drying oven, obtain core-shell nano, the quality of described cetrimonium bromide and the volume ratio of water A are 1mg:(0.03 ~ 0.05) mL, the volume ratio of the up-conversion nanoparticles core that the quality of described cetrimonium bromide and step one obtain is 1mg:(0.003 ~ 0.005) mL, the quality of described cetrimonium bromide and the volume ratio of water B are 1mg:(0.05 ~ 0.15) mL, the quality of described cetrimonium bromide and concentration are the volume ratio of the tetraethoxysilane alcoholic solution of 25% is 1mg:(0.03 ~ 0.07) mL, the volume ratio of the photosensitizer condensation solution that the quality of described cetrimonium bromide and step 2 obtain is 1mg:(0.03 ~ 0.07) mL.
A kind of application with the nuclear shell structure drug carrier of near infrared light remote response is used for suppressing and killing and wounding atheromatous plaque cell as pharmaceutical carrier by the nuclear shell structure drug carrier with near infrared light remote response, concrete using method is as follows: Xiang Shuizhong adds core-shell nano and obtains the core-shell nano that concentration is 12 μ g/mL ~ 16 μ g/mL, be after the core-shell nano of 12 μ g/mL ~ 16 μ g/mL and macrophage Dual culture 4h by concentration, the concentration of not engulfed by cell surface with buffer memory solution is that the core-shell nano of 12 μ g/mL ~ 16 μ g/mL washes away, laser power is adopted to be 0.9W cm
-2~ 1.8W cm
-2's
closelyiraser irradiates the macrophage in 96 orifice plates, and irradiation time is 1min.
Operation principle:
The present invention is with rear-earth-doped upper conversion particles (NaYF
4: Yb, Er) be core, the near infrared light of incidence is converted to green glow and HONGGUANG in vivo by upper conversion core, wherein 540nm green glow can be used for cell imaging, and 660nm HONGGUANG excites photosensitizer to produce singlet oxygen, macrophage is killed and wounded, outer field mesoporous silicon oxide shell, be used to load photosensitizer (chlorin e 6, Ce6), photosensitizer is embedded in silicon dioxide by the mode of chemical bonding, the coated biocompatibility problem of poor not only solving up-conversion nanoparticles and photosensitizer of silica shell, silicon shell outer surface has the phagocytosis that polyhydroxy structure is more suitable for macrophage simultaneously, nanoparticle is more easily engulfed by atherosclerosis plaque cells, there is certain targeting.Nanoparticle, under the irradiation of near infrared light, produces active oxygen species thus kills and wounds atheromatous plaque cell, causing plaque apoptosis, thus suppresses the formation of atheromatous plaque, has prevention and treatment concurrently simultaneously.Here the optical dynamic therapy illustrated is needed to be wish atheromatous plaque apoptosis but not downright bad.Both difference are, no longer merisis after apoptosis, but organizational structure is preserved, and after necrocytosis, organizational structure is downright bad, can cause the other problemses such as inflammation.
Beneficial effect of the present invention:
The present invention is based on the feature that near infrared light organism penetration power is strong, utilize rear-earth-doped up-conversion nanoparticles as nanometer transducer, near infrared light is changed into the visible ray that can excite photosensitizer and ultraviolet light, original position excites photosensitizer to produce singlet oxygen, cause plaque apoptosis, thus suppress the formation of atheromatous plaque, auxiliary treatment and necessary complement can be treated as mechanical intervention, have prevention and treatment treatment concurrently applied widely: do not rely on intracellular environment, be applicable to cell and experiment made on the living.Its treatment precision is high, and error is little, reproducible.Light-operated response timing location produces singlet oxygen molecular, avoids Normocellularly killing and wounding other.
Core-shell nano prepared by the present invention has better selectivity for macrophage, avoids Normocellularly killing and wounding other.The preparation of this nuclear shell structure nano diagnosis and treatment platform is directly simple, easily operates, practical.
Accompanying drawing explanation
Fig. 1 is the transmission electron microscope shape appearance figure of the core-shell nano that embodiment one obtains;
Fig. 2 is the spectrogram of the chlorin e 6 ultravioletvisible absorption described in embodiment one step 2;
Fig. 3 is the fluorescence spectrum figure of core-shell nano under near infrared light excites that embodiment one obtains;
Fig. 4 is the detection curve of the core-shell nano singlet oxygen generation that under near infrared light, embodiment one obtains, and wherein each bar curve is in the direction of the arrow for the concentration of singlet oxygen probe arranges from low to high;
Fig. 5 is the transmission electron microscope picture without the macrophage of any process in embodiment three;
Fig. 6 is to be 1.8W cm without the macrophage of any process in laser power in embodiment three
-2's
closelythe postradiation transmission electron microscope picture of iraser;
Fig. 7 is embodiment three core-shell nano is 1.8W cm in laser power after macrophage phagocytic
-2's
closelythe postradiation transmission electron microscope picture of iraser.
Detailed description of the invention
Detailed description of the invention one: a kind of preparation method with the nuclear shell structure drug carrier of near infrared light remote response of present embodiment is specifically carried out according to the following steps:
One, by NaYF
4: Yb/Er up-conversion nanoparticles is scattered in cyclohexane extraction, obtains up-conversion nanoparticles core;
Two, in DMF solvent, add dicyclohexylcarbodiimide, chlorin e 6 and 3-aminopropyl triethoxysilane successively, obtain mixed solution, mixed solution is at room temperature left standstill 24h, obtains photosensitizer condensation solution; The quality of described dicyclohexylcarbodiimide and the volume ratio of DMF solvent are 1mg:(1.5 ~ 2) mL; The quality of described chlorin e 6 and the volume ratio of DMF solvent are 1mg:(0.5 ~ 0.8) mL; The volume ratio of described 3-aminopropyl triethoxysilane and DMF solvent is 1:(180 ~ 220);
Three, cetrimonium bromide is joined stirring and dissolving in solvent orange 2 A, then the up-conversion nanoparticles core that step one obtains is added wherein, ultrasonic 30min after stirring 30min, obtain ultrasonic solution, be heat 30min under the condition of 80 DEG C in ultrasonic solution, to add solvent B after ultrasonic solution is transparent in temperature, and be 9 with the pH of sodium hydroxide solution adjustment ultrasonic solution, adopting peristaltic pump in ultrasonic solution, add concentration is after the tetraethoxysilane alcoholic solution of 25%, add the photosensitizer condensation solution that step 2 obtains again, after at room temperature reacting 24h, solid is obtained by centrifugalize, solid is adopted ethanol purge 3 ~ 5 times, then vacuum drying 24h in vacuum drying oven, obtain core-shell nano, the quality of described cetrimonium bromide and the volume ratio of water A are 1mg:(0.03 ~ 0.05) mL, the volume ratio of the up-conversion nanoparticles core that the quality of described cetrimonium bromide and step one obtain is 1mg:(0.003 ~ 0.005) mL, the quality of described cetrimonium bromide and the volume ratio of water B are 1mg:(0.05 ~ 0.15) mL, the quality of described cetrimonium bromide and concentration are the volume ratio of the tetraethoxysilane alcoholic solution of 25% is 1mg:(0.03 ~ 0.07) mL, the volume ratio of the photosensitizer condensation solution that the quality of described cetrimonium bromide and step 2 obtain is 1mg:(0.03 ~ 0.07) mL.
Described solvent orange 2 A and solvent B are water.
Present embodiment is based on the strong feature of near infrared light organism penetration power, utilize rear-earth-doped up-conversion nanoparticles as nanometer transducer, near infrared light is changed into the visible ray that can excite photosensitizer and ultraviolet light, original position excites photosensitizer to produce singlet oxygen, cause plaque apoptosis, thus suppress the formation of atheromatous plaque, auxiliary treatment and necessary complement can be treated as mechanical intervention, have prevention and treatment treatment concurrently applied widely: do not rely on intracellular environment, be applicable to cell and experiment made on the living.Its treatment precision is high, and error is little, reproducible.Light-operated response timing location produces singlet oxygen molecular, avoids Normocellularly killing and wounding other.
Core-shell nano prepared by present embodiment has better selectivity for macrophage, avoids Normocellularly killing and wounding other.The preparation of this nuclear shell structure nano diagnosis and treatment platform is directly simple, easily operates, practical.
Detailed description of the invention two: present embodiment and detailed description of the invention one unlike: the quality of dicyclohexylcarbodiimide described in step 2 and the volume ratio of dicyclohexylcarbodiimide solvent are 1mg:1.7mL.Other steps and parameter identical with detailed description of the invention one.
Detailed description of the invention three: present embodiment and detailed description of the invention one or two unlike: the quality of chlorin e 6 described in step 2 and the volume ratio of dicyclohexylcarbodiimide solvent are 1mg:0.625mL.Other steps and parameter identical with detailed description of the invention one or two.
Detailed description of the invention four: one of present embodiment and detailed description of the invention one to three unlike: the volume ratio of the aminopropyl triethoxysilane of 3-described in step 2 and dicyclohexylcarbodiimide solvent is 1:200.Other steps and parameter identical with one of detailed description of the invention one to three.
Detailed description of the invention five: one of present embodiment and detailed description of the invention one to four unlike: the quality of cetrimonium bromide described in step 3 and the volume ratio of water A are 1mg:0.04mL.Other steps and parameter identical with one of detailed description of the invention one to four.
Detailed description of the invention six: one of present embodiment and detailed description of the invention one to five unlike: the volume ratio of the up-conversion nanoparticles core that the quality of cetrimonium bromide described in step 3 and step one obtain is 1mg:0.004mL.Other steps and parameter identical with one of detailed description of the invention one to five.
Detailed description of the invention seven: one of present embodiment and detailed description of the invention one to six unlike: the quality of cetrimonium bromide described in step 3 and the volume ratio of water B are 1mg:0.1mL.Other steps and parameter identical with one of detailed description of the invention one to six.
Detailed description of the invention eight: one of present embodiment and detailed description of the invention one to seven unlike: the quality of cetrimonium bromide described in step 3 and concentration are the volume ratio of the tetraethoxysilane alcoholic solution of 25% is 1mg:0.05mL.Other steps and parameter identical with one of detailed description of the invention one to seven.
Detailed description of the invention nine: one of present embodiment and detailed description of the invention one to eight unlike: the volume ratio of the photosensitizer condensation solution that the quality of cetrimonium bromide described in step 3 and step 2 obtain is 1mg:0.05mL.Other steps and parameter identical with one of detailed description of the invention one to eight.
Detailed description of the invention ten: a kind of application with the nuclear shell structure drug carrier of near infrared light remote response of present embodiment is used for suppressing and killing and wounding atheromatous plaque cell as pharmaceutical carrier by the nuclear shell structure drug carrier with near infrared light remote response, concrete using method is as follows: Xiang Shuizhong adds core-shell nano and obtains the core-shell nano that concentration is 12 μ g/mL ~ 16 μ g/mL, be after the core-shell nano of 12 μ g/mL ~ 16 μ g/mL and macrophage Dual culture 4h by concentration, the concentration of not engulfed by cell surface with buffer memory solution is that the core-shell nano of 12 μ g/mL ~ 16 μ g/mL washes away, laser power is adopted to be 0.9W cm
-2~ 1.8W cm
-2's
closelyiraser irradiates the macrophage in 96 orifice plates, and irradiation time is 1min.
Beneficial effect of the present invention is verified by following examples
Embodiment one: a kind of preparation method with the nuclear shell structure drug carrier of near infrared light remote response of the present embodiment is specifically carried out according to the following steps:
One, by six chloride hydrate yttrium (0.237mg, 0.78mmol), six hydrous ytterbium chloride (0.0775mg, 0.2mmol) He six water Erbium trichloride (0.0077mg, 0.02mmol) together join in three mouthfuls of round-bottomed flasks of 250mL, then add oleic acid (6mL) and octadecylene (5mL); When logical argon, stirred by mixture and be heated to 160 degrees Celsius of maintenances 30 minutes, add 10mL octadecylene more subsequently, mixture naturally cools to 50 DEG C stir 1h under temperature is the condition of 160 DEG C after; Ammonium fluoride (the 148.16mg that methanol (10mL) dissolves is added in mixture, 4mmol) with sodium hydroxide (100mg, 2.5mmol) solution, 50 DEG C are kept to stir 30min nucleation, at 70 DEG C, methanol is boiled off afterwards, mixture be heated to rapidly 300 DEG C and keep 1h under magnetic stirring, after reaction terminates, mixture being down to room temperature naturally, add ethanol, product centrifuge is centrifugal under 10000 turns, uses ethanol purge solid, this process 3 times repeatedly.The yttrium fluoride natrium nanoparticle dispersion finally obtained, in 10mL cyclohexane extraction, obtains up-conversion nanoparticles core;
Two, to 10mLN, 5.6mg dicyclohexylcarbodiimide, 16mg chlorin e 6,50 μ L 3-aminopropyl triethoxysilanes are added successively in dinethylformamide solvent, obtain mixed solution, mixed solution is at room temperature left standstill 24h, obtains photosensitizer condensation solution;
Three, 200mg cetrimonium bromide is joined stirring and dissolving in 8mL water, then the up-conversion nanoparticles core that 800 μ L steps one obtain is added wherein, ultrasonic 30min after stirring 30min, obtain ultrasonic solution, be heat 30min under the condition of 80 DEG C in ultrasonic solution, to add 20mL water after ultrasonic solution is transparent in temperature, and be 9 with the pH of sodium hydroxide solution adjustment ultrasonic solution, adopting peristaltic pump in ultrasonic solution, add 1mL concentration is after the tetraethoxysilane alcoholic solution of 25%, add the photosensitizer condensation solution that 1mL step 2 obtains again, after at room temperature reacting 24h, solid is obtained by centrifugalize, solid is adopted ethanol purge 3 ~ 5 times, then vacuum drying 24h in vacuum drying oven, obtain core-shell nano.
Fig. 1 is the transmission electron microscope shape appearance figure of the core-shell nano that embodiment one obtains; As can be seen from the figure the core-shell nano that obtains of embodiment one, rear-earth-doped upper conversion particles (NaYF
4: Yb, Er) core is of a size of 30nm, and the shell structure of coated mesoporous silicon oxide is of a size of 50nm.
Fig. 2 is the spectrogram of the chlorin e 6 ultravioletvisible absorption described in embodiment one step 2; Fig. 3 is the fluorescence spectrum figure of core-shell nano under near infrared light excites that embodiment one obtains; As can be seen from Figure 2 the absorption maximum of photosensitizer chlorin e 6 in red light region is at 660 ran, and the core-shell nano that can obtain with embodiment in Fig. 3 one is in the emission spectra Perfect Matchings of red light region.This phenomenon proves that the light that the core-shell nano that embodiment one obtains is launched well can be absorbed by photosensitizer, and then produces singlet oxygen by the mode of FRET (fluorescence resonance energy transfer), killer macrophage.
Fig. 4 is the detection curve of the core-shell nano singlet oxygen generation that under near infrared light, embodiment one obtains, and wherein each bar curve is in the direction of the arrow for the concentration of singlet oxygen probe arranges from low to high; Because singlet oxygen can generate another material with probe reaction, the ultravioletvisible absorption of probe is obviously reduced as can be seen from Figure 4, so measure in singlet oxygen responsive probe 9,10-anthryl-bis-(methylene) two malonic acid (ABDA) is deposited in case, nanoparticle excites through near infrared light, the ultravioletvisible absorption of Timing measurement solution middle probe, the obvious of concentration and probe concentration reduces the lasting generation proving singlet oxygen molecular.
Embodiment two: a kind of application with the nuclear shell structure drug carrier of near infrared light remote response of the present embodiment: Xiang Shuizhong adds core-shell nano and obtains the core-shell nano that concentration is 16 μ g/mL, by concentration be 16 μ g/mL core-shell nano with without after the macrophage Dual culture 4h of any process, the concentration of not engulfed by cell surface with buffer memory solution is that the core-shell nano of 16 μ g/mL washes away, and adopts laser power to be 0.9W cm
-2's
closelyiraser irradiates the macrophage in 96 orifice plates, and irradiation time is 1min.Then mtt assay sign is carried out to cell survival rate and apoptosis rate.
Embodiment three: a kind of application with the nuclear shell structure drug carrier of near infrared light remote response of the present embodiment: Xiang Shuizhong adds core-shell nano and obtains the core-shell nano that concentration is 16 μ g/mL, by concentration be 16 μ g/mL core-shell nano with without after the macrophage Dual culture 4h of any process, the concentration of not engulfed by cell surface with buffer memory solution is that the core-shell nano of 16 μ g/mL washes away, and adopts laser power to be 1.8W cm
-2's
closelyiraser irradiates the macrophage in 96 orifice plates, and irradiation time is 1min.Then mtt assay sign is carried out to cell survival rate and apoptosis rate.
Fig. 5 is the transmission electron microscope picture without the macrophage of any process in embodiment three; Fig. 6 is to be 1.8W cm without the macrophage of any process in laser power in embodiment three
-2's
closelythe postradiation transmission electron microscope picture of iraser; Fig. 7 is embodiment three core-shell nano is 1.8W cm in laser power after macrophage phagocytic
-2's
closelythe postradiation transmission electron microscope picture of iraser; Can find out that from Fig. 5 ~ 7 cell of independent illumination undressed macrophage and firm power all maintains the normal sign of cell, remain complete cell membrane form, there is abundant cell fine hair, fine and close Cytoplasm and complete nuclear structures.This result shows that laser irradiation power is at 1.8W cm
-2time macrophage be perfectly safe.And the laser of the macrophage having engulfed nanoparticle under similarity condition is when irradiating, cellular morphology obviously there occurs change, such as the disappearance of cell fine hair, the reduction of nucleus volume and the chromatinic atrophy of nuclear membrane coker.This result show test synthesis nanoparticle within the scope of safe concentration after macrophage selectivity is engulfed, use safety laser power is irradiated can cause macrophage apoptosis (non-necrosis), thus delays further developing of atheromatosis.
Under equal-wattage after variable concentrations nanoparticle and macrophage Dual culture certain hour, to apply in two kinds of safety rangies near infrared light power density irradiating cell 1 minute, cell is subject to killing and wounding in various degree, under valid density, relatively large near-infrared power has better effect, reason is that laser power is larger, and the efficiency producing singlet oxygen is higher, thus apoptosis rate is higher.
Claims (10)
1. there is a preparation method for the nuclear shell structure drug carrier of near infrared light remote response, it is characterized in that what the preparation method of the nuclear shell structure drug carrier with near infrared light remote response was specifically carried out according to the following steps:
One, by NaYF
4: Yb/Er up-conversion nanoparticles is scattered in cyclohexane extraction, obtains up-conversion nanoparticles core;
Two, in DMF solvent, add dicyclohexylcarbodiimide, chlorin e 6 and 3-aminopropyl triethoxysilane successively, obtain mixed solution, mixed solution is at room temperature left standstill 24h, obtains photosensitizer condensation solution; The quality of described dicyclohexylcarbodiimide and the volume ratio of DMF solvent are 1mg:(1.5 ~ 2) mL; The quality of described chlorin e 6 and the volume ratio of DMF solvent are 1mg:(0.5 ~ 0.8) mL; The volume ratio of described 3-aminopropyl triethoxysilane and DMF solvent is 1:(180 ~ 220);
Three, cetrimonium bromide is joined stirring and dissolving in solvent orange 2 A, then the up-conversion nanoparticles core that step one obtains is added wherein, ultrasonic 30min after stirring 30min, obtain ultrasonic solution, be heat 30min under the condition of 80 DEG C in ultrasonic solution, to add solvent B after ultrasonic solution is transparent in temperature, and be 9 with the pH of sodium hydroxide solution adjustment ultrasonic solution, adopting peristaltic pump in ultrasonic solution, add concentration is after the tetraethoxysilane alcoholic solution of 25%, add the photosensitizer condensation solution that step 2 obtains again, after at room temperature reacting 24h, solid is obtained by centrifugalize, solid is adopted ethanol purge 3 ~ 5 times, then vacuum drying 24h in vacuum drying oven, obtain core-shell nano, the quality of described cetrimonium bromide and the volume ratio of water A are 1mg:(0.03 ~ 0.05) mL, the volume ratio of the up-conversion nanoparticles core that the quality of described cetrimonium bromide and step one obtain is 1mg:(0.003 ~ 0.005) mL, the quality of described cetrimonium bromide and the volume ratio of water B are 1mg:(0.05 ~ 0.15) mL, the quality of described cetrimonium bromide and concentration are the volume ratio of the tetraethoxysilane alcoholic solution of 25% is 1mg:(0.03 ~ 0.07) mL, the volume ratio of the photosensitizer condensation solution that the quality of described cetrimonium bromide and step 2 obtain is 1mg:(0.03 ~ 0.07) mL.
2. a kind of preparation method with the nuclear shell structure drug carrier of near infrared light remote response according to claim 1, it is characterized in that the quality of dicyclohexylcarbodiimide described in step 2 and the volume ratio of DMF solvent are 1mg:1.7mL.
3. a kind of preparation method with the nuclear shell structure drug carrier of near infrared light remote response according to claim 1, is characterized in that the quality of chlorin e 6 described in step 2 and the volume ratio of DMF solvent are 1mg:0.625mL.
4. a kind of preparation method with the nuclear shell structure drug carrier of near infrared light remote response according to claim 1, is characterized in that the volume ratio of the aminopropyl triethoxysilane of 3-described in step 2 and DMF solvent is 1:200.
5. a kind of preparation method with the nuclear shell structure drug carrier of near infrared light remote response according to claim 1, is characterized in that the quality of cetrimonium bromide described in step 3 and the volume ratio of solvent orange 2 A are 1mg:0.04mL.
6. a kind of preparation method with the nuclear shell structure drug carrier of near infrared light remote response according to claim 1, is characterized in that the volume ratio of the up-conversion nanoparticles core that the quality of cetrimonium bromide described in step 3 and step one obtain is 1mg:0.004mL.
7. a kind of preparation method with the nuclear shell structure drug carrier of near infrared light remote response according to claim 1, is characterized in that the quality of cetrimonium bromide described in step 3 and the volume ratio of solvent B are 1mg:0.1mL.
8. a kind of preparation method with the nuclear shell structure drug carrier of near infrared light remote response according to claim 1, is characterized in that the quality of cetrimonium bromide described in step 3 and concentration be the volume ratio of the tetraethoxysilane alcoholic solution of 25% are 1mg:0.05mL.
9. a kind of preparation method with the nuclear shell structure drug carrier of near infrared light remote response according to claim 1, is characterized in that the volume ratio of the photosensitizer condensation solution that the quality of cetrimonium bromide described in step 3 and step 2 obtain is 1mg:0.05mL.
10. a kind of application with the nuclear shell structure drug carrier of near infrared light remote response as claimed in claim 1, it is characterized in that the application of the nuclear shell structure drug carrier with near infrared light remote response is used for suppressing and killing and wounding atheromatous plaque cell as pharmaceutical carrier by the nuclear shell structure drug carrier with near infrared light remote response, concrete using method is as follows: Xiang Shuizhong adds core-shell nano and obtains the core-shell nano that concentration is 12 μ g/mL ~ 16 μ g/mL, be after the core-shell nano of 12 μ g/mL ~ 16 μ g/mL and macrophage Dual culture 4h by concentration, the concentration of not engulfed by cell surface with buffer memory solution is that the core-shell nano of 12 μ g/mL ~ 16 μ g/mL washes away, laser power is adopted to be 0.9W cm
-2~ 1.8W cm
-2's
closelyiraser irradiates the macrophage in 96 orifice plates, and irradiation time is 1min.
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| CN109337356A (en) * | 2018-10-24 | 2019-02-15 | 杨定吉甫 | It is a kind of can laser color label the composition for optical fiber laser |
| CN111632072A (en) * | 2020-06-10 | 2020-09-08 | 华中科技大学同济医学院附属协和医院 | Therapeutic liquid for treating ischemic stroke and preparation method and application thereof |
| CN113827721A (en) * | 2020-06-23 | 2021-12-24 | 中国科学院宁波工业技术研究院慈溪生物医学工程研究所 | Application of nano material in preparation of medicine for treating atherosclerosis |
| CN115364239A (en) * | 2022-06-02 | 2022-11-22 | 徐州医科大学 | Nano particles with function of realizing imaging of targeted vulnerable atherosclerotic plaque as well as preparation method and application of nano particles |
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| CN109337356A (en) * | 2018-10-24 | 2019-02-15 | 杨定吉甫 | It is a kind of can laser color label the composition for optical fiber laser |
| CN109337356B (en) * | 2018-10-24 | 2020-10-20 | 浙江优可丽新材料有限公司 | Composition capable of being subjected to laser color marking and used for fiber laser |
| CN111632072A (en) * | 2020-06-10 | 2020-09-08 | 华中科技大学同济医学院附属协和医院 | Therapeutic liquid for treating ischemic stroke and preparation method and application thereof |
| CN113827721A (en) * | 2020-06-23 | 2021-12-24 | 中国科学院宁波工业技术研究院慈溪生物医学工程研究所 | Application of nano material in preparation of medicine for treating atherosclerosis |
| CN115364239A (en) * | 2022-06-02 | 2022-11-22 | 徐州医科大学 | Nano particles with function of realizing imaging of targeted vulnerable atherosclerotic plaque as well as preparation method and application of nano particles |
| CN115364239B (en) * | 2022-06-02 | 2024-01-30 | 徐州医科大学 | Nanoparticle capable of achieving imaging by targeting vulnerable atherosclerosis plaque and preparation method and application thereof |
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