CN104840977B - A kind of preparation method of magnetic fluorescence composite Nano pharmaceutical carrier - Google Patents
A kind of preparation method of magnetic fluorescence composite Nano pharmaceutical carrier Download PDFInfo
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Abstract
The present invention relates to a kind of preparation method of magnetic fluorescence composite Nano pharmaceutical carrier, the present invention substantially improves encapsulating effect from the beta cyclodextrin derivative parcel hydrophobic drug with inner chamber molecular structure.The magnetic nano-particle that the carrier structure is modified using negatively charged carboxymethyl chitosan or carboxymethyl beta cyclodextrin is core, then in diallyl dimethyl ammoniumchloride（PDDA）, ion crosslinking agent and carrying medicament anionic macromolecule organic in the presence of, water-soluble quantum dot is connected by ionic cross-linking and obtains magnetic fluorescence composite nanometer particle.Fluorescence quantum of the present invention is evenly distributed on the surface of magnetic nanoparticle, and the wherein particle size of magnetic nanoparticle is in 10 200 nm, and the particle diameter of quantum dot is in 1.5 10 nm.Reaction condition of the present invention is gentle, operating method is simple, composite Nano pharmaceutical carrier has good biocompatibility and hydrophily, the controllable encapsulation to tumour medicine and release can be achieved, there is magnetic targeted and fluorescent tracing function simultaneously, there is important research and application value with the association area such as separating in the monitoring of pharmaceutical carrier, bio-imaging and biomolecule.
Description
Technical field
The present invention relates to a kind of preparation method of multi-functional, hydrophobic pharmaceutical carrier, and in particular to a kind of magnetic fluorescence is compound
The preparation method of nano-medicament carrier, the composite Nano pharmaceutical carrier have been provided simultaneously with the fluorescence property and magnetic Nano of quantum dot
The magnetic property of particle, it can be used as targeting positioning and bioluminescence imaging aspect in organism.
Background technology
Tumour is one of current major disease for threatening human health, treats the commonsense method radiotherapy of tumour, changes
Learning medicinal treatment, heat therapy and surgery excision etc. has certain limitation, as radiation and chemotherapy is killing the same of tumour cell
When, it can also damage normal human cell.Therefore, for a long time it is intended that chemotherapy and radiation medicine direction and location is transported to
Specific lesion tissue and organ, realize the purpose of local patholoic change local treatment.Carried in consideration of it, developing a kind of multifunctional drug
Body, by cleverly designing, multiple functional supports materials are integrated in single and stable system, to reach specific purpose,
Such as extend blood circulation time, targeting, drug controlled release while load therapeutic agent, developer or contrast agent.Pass through
The form of chemical bonding, physical absorption or parcel forms unique medicine control system with drug molecule, and the nanometer medicine of synthesis carries
Have both the characteristics such as drugloading rate high, targeting is good, toxicity is low, controlled release, being capable of timing, positioning, quantitative performance drug effect.
In many fields, especially biomedical fields go out obvious advantage for quantum dot and magnetics nanoparticle.
But they often only have single function, the fluorescence labeling of such as quantum dot, the Magnetic Isolation of magnetic particle, if by two kinds
Function-separation and mark function are dissolved in one, prepare new magnetic fluorescence nano by certain physical and chemical process and answer
Condensation material, while making it as fluorescence probe, also with good magnetic response characteristic.Therefore, magnetic fluorescence nano particle has
There are Magneto separate and fluorescent tracing dual-use function, its performance and application are all considerably beyond the nano-particle of simple function, no
The detection and separation on bio-molecular level can only be carried out；Also achieve various modes imaging, i.e., fluorescence imaging, magnetic resonance into
As (MRI) and Laser scanning confocal microscopy.Now with going deep into for composite nanometer particle research, this composite particles are in medicine
Had a clear superiority in targeting transportation, because composite nanometer particle can utilize fluorescence while targeting conveying is realized
Label imaging technique, course of conveying to medicine and is monitored in real time with the mechanism of cell, is discharged in drug targeting
While further study the antitumor machanism of drug molecule, therefore in biomedical sector, hence it is evident that improve bioanalysis and
The speed and accuracy rate of medical diagnosis.
There is a research surface, for beta-schardinger dextrin as a kind of supramolecular materials, it has the structure that outer rim is hydrophilic and inner chamber is hydrophobic,
Thus it can provide a hydrophobic binding site as enzyme, and various appropriate objects, such as organic point are included as main body
Son, inorganic ions and drug molecule etc..Meanwhile as pharmaceutical carrier, it can not only be formed and included with the material of poorly water-soluble
Thing, and the encapsulating of some water-soluble substanceses can be promoted.Carboxymethyl-beta-cyclodextrin and Sulfobutyl ether β _ cyclodextrin are pasted as ring
The derivative of essence, self-contained negative electrical charge can be with the diallyl dimethyl ammoniumchloride with positive charge（PDDA）By quiet
It is electrically coupled to form composite nanometer particle, its distinctive inner chamber hydrophobic structure can form inclusion compound with some hydrophobic drugs,
So that the encapsulating effect of such material significantly improves.Medicine is after cyclodextrin encapsulated, its chemical stability, solubility property, biology
Availability significantly improves.
The content of the invention
Prepared it is an object of the invention to provide a kind of ionic cross-linking and integrate the more of magnetic, fluorescence and drug loading
The method of the preparation of function nano pharmaceutical carrier, composite Nano pharmaceutical carrier prepared by this method have that magnetic responsiveness is strong, light is steady
It is qualitative it is high, the high preparation technology of drug loading is simple, good dispersion and the advantages that size uniform, have in field of nano biotechnology
There is wider application.
The present invention is achieved by the following measures：
A kind of preparation method of magnetic fluorescence composite Nano pharmaceutical carrier, using following steps：
（a）Negatively charged magnetic nanocomposites are prepared using blending investment：
1. weighing 50-500mg magnetic nanoparticles is dissolved in 30 mL pH=7.4, the PBS that concentration is 0.01mol/L is buffered
In solution, lead to nitrogen deoxidation, magnetic particle is uniformly dispersed using supersonic wave cleaning machine；2. weigh 10-800 mg carboxymethyl shells
Glycan or carboxymethyl-beta-cyclodextrin are dissolved in the cushioning liquid of 20 mL PBS=7.4, at the same add 0.1-0.5 g 1- ethyls-
（3- dimethylaminopropyls）Carbodiimide hydrochloride（EDAC）Activate carboxymethyl chitosan or carboxymethyl-beta-cyclodextrin surface
Group；1. and 2. 3. two solution will mix, 25 DEG C of vibration 2-6 h in thermostatic control oscillator vibration, then distilled water and PBS are used successively
(pH=7.4) cushioning liquid fully washs, that is, obtains negatively charged magnetic nanocomposites；
（b）Magnetic fluorescence composite Nano pharmaceutical carrier is prepared using ionic cross-linking：
Take the aqueous phase quantum point of the concentration of preparation to be dissolved in distilled water, add ion crosslinking agent, obtain reaction solution A；Will
The ethanol solution of hydrophobic drug mixes with anionic macromolecule organic, oscillating reactions 2-10 h under normal temperature, comprising
The inclusion compound B of medicine；Take 0.005-0.05g steps（a）The negatively charged magnetic nanocomposites of middle preparation are dissolved in distilled water
In, ultrasonic 20-60 min, magnetic nanometer particles is uniformly dispersed, and add diallyl dimethyl ammoniumchloride and reacted
Solution C；Reaction solution A and B are added dropwise in reaction solution C, oscillating reactions 2-10 h under normal temperature, centrifuged, distillation
Water washing, that is, obtain magnetic fluorescence composite Nano pharmaceutical carrier.
Prepared by magnetic fluorescence composite Nano pharmaceutical carrier of the present invention, the particle diameter of composite Nano pharmaceutical carrier is 10-
220 nm；Magnetic nanoparticle（MNPs）For superparamagnetic, paramagnetic or ferromagnetic metal and metal oxide, selected from Fe3O4、
Fe2O3、MeFe2O4(Me=Co, Mn, Ni), compound neodymium iron boron, SmCo etc., metal Fe, Co, Ni and alloy Fe2Co、Ni2Fe
Metal oxide nano particle in one kind；The preparation method of magnetic nanoparticle includes coprecipitation, hydro-thermal method；Magnetic
Nano grain surface contains at least one of hydroxyl, amino, carboxyl.
Quantum dot of the present invention is the water-soluble quantum dot that surface carries hydrophilic radical, and quantum dot is II-VI group half
Conductor material, or the composite formed for Group II-VI semiconductor material, the quantum point grain diameter is 1.5-10 nm；It is preferred that
Quantum dot be ZnSe, CdSe, CdTe, CdS, ZnSe/ZnS, CdS/ZnS, CdSe/ZnS, CdTe/ZnS, ZnXCd1-XSe、
CdSe1-XSX、CdSe1-XTeX、CdSe/ZnSe、CdS/ZnSe、CdTe/ZnSe、CdSe/CdS、CdTe/CdS、CdS/ZnXCd1- XS、ZnSe/ZnXCd1-XS、CdSe/ZnXCd1-XS or CdTe/ZnXCd1-XOne kind in S, wherein 0 ＜ X ＜ 1.
Ion crosslinking agent of the present invention include tripolyphosphate, four Quadrafos, hexametaphosphate, pyrophosphate,
One or more in molybdate, hyaluronic acid or gamma-polyglutamic acid；Anionic macromolecule organic carboxymethyl-β-ring paste
Essence or Sulfobutyl ether β _ cyclodextrin；O-CMC or N, O-CMC can be selected in carboxymethyl chitosan；Poly- two
The molecular weight and mass concentration of allyl dimethyl ammonium chloride are respectively 1 × 105-2×105With 0.51-5.1 mg/mL.
Hydrophobic drug of the present invention includes brufen, 5 FU 5 fluorouracil, Docetaxel, camptothecine or taxol
At least one of.
A kind of preparation of magnetic fluorescence composite Nano pharmaceutical carrier of the present invention, step（a）Middle carboxymethyl chitosan
Or thickness of the carboxymethyl-beta-cyclodextrin on magnetic nanoparticle surface is 3-10 nm；Step（b）Middle hydrophobic drug with it is cloudy from
The mol ratio of subtype macromolecule organic is 1:10-1:60, the mol ratio of negatively charged magnetic nanocomposites and quantum dot
For 1:1-1:20, diallyl dimethyl ammoniumchloride：Anionic macromolecule organic：The mass ratio of ion crosslinking agent is 1:
0.1-2:0.01-0.5。
Quantum dot surface of the present invention contains at least one of sulfydryl, carboxyl, amino；In semiconductor-quantum-point synthesis
Used hydrophilic radical part includes 3- mercaptopropionic acids, TGA, Cys, 2 mercaptopropionic acid, mercaptobutyric acid, mercapto
One kind or several in base valeric acid, mercaptohexanoic acid, dimercaptosuccinic acid, mercaptoethanol, glutathione, mercaprol or mercaptoethylmaine
Kind.
Beneficial effects of the present invention：
（1）The present invention is assembled into magnetic fluorescence by ionic cross-linking using the polyelectrolyte effect between opposite charges material
Composite Nano pharmaceutical carrier, without using organic solvent, reaction condition is gentle, can protect the activity of drug molecule to greatest extent；
（2）Present invention selection diallyl dimethyl ammoniumchloride（PDDA）As cationic polyelectrolyte, it has peace
The characteristics such as entirely, nontoxic, soluble in water and hydrolytic stability is good, cohesiveness is strong, avoid and use other organic polyelectrolytes
Caused by bio-toxicity；
（3）Carboxymethyl-beta-cyclodextrin or Sulfobutyl ether β _ cyclodextrin embedding of the present invention selection with inner chamber molecular structure are dredged
Aqueous pharmaceutical, there is preferable encapsulating to act on to hydrophobic active, improve the solubility of medicine, increase medicine stability, drop
The adverse reaction of low medicine；
（4）Multifunctional composite nanometer pharmaceutical carrier prepared by the present invention, it is possible to achieve while targeted drug delivery, utilize
Fluorescent labelling techniques, the mechanism of course of conveying and cell to medicine are monitored in real time, hence it is evident that improve bioanalysis
With the speed and accuracy rate of medical diagnosis.
Brief description of the drawings
The abosrption spectrogram of Fig. 1 magnetic fluorescence composite Nano pharmaceutical carrier insoluble drug releases
The TEM photos of Fig. 2 magnetic fluorescence composite Nano pharmaceutical carriers
The hysteresis curve of Fig. 3 magnetic fluorescence composite Nano pharmaceutical carriers
The Absorption and fluorescence spectrum of Fig. 4 magnetic fluorescence composite Nano pharmaceutical carriers
Digital photograph of Fig. 5 magnetic fluorescence composite Nano pharmaceutical carriers in uviol lamp and externally-applied magnetic field.
Embodiment
Illustrate technical scheme below by specific embodiment, but technical scheme is not with specific real
Example is applied to be limited.
Embodiment 1：
1.1 aqueous phases prepare CdTe quantum.Under nitrogen protection, by 0.0945g NaBH4It is dissolved in 0.0063g Te powder
In 5 mL distilled water, 40 DEG C are heated to, NaHTe solution is obtained after being completely dissolved；Take 0.293 g Cd (Ac)2Dissolve in 100 mL steamings
In distilled water, 2.0 mmol TGAs are added after it is completely dissolved, pH=11 is adjusted with 1mol/L NaOH solution, obtains Cd
Precursor solution；Cd presoma is transferred in there-necked flask, injects NaHTe solution, 100 DEG C of oil bath rapidly under nitrogen protection
Flow back, taking-up, which is put into refrigerator, after magnetic agitation 2h is quickly cooled to room temperature, obtains red, transparent solution, as prepares
CdTe QDs solution.
1.2 prepare Fe using hydro-thermal method3O4Nano particle.Weigh 3 g FeCl3It is dissolved in 80 mL ethylene glycol and stirs ultrasound
Dissolving, adds the g of polyethylene glycol 2, the g of sodium acetate 7 that molecular weight is 2000, and stirring ultrasound is allowed to dissolve, precursor solution is turned
Enter in hydrothermal reaction kettle, react 4 h at 200 DEG C, resulting solution water is replaced into washing with absolute ethyl alcohol after the completion of reaction, through true
Sky is dried, and obtains dry Fe3O4Magnetic nanoparticle.
1.3 prepare negatively charged magnetic nanocomposites using blending investment.Weigh 0.08 g Fe3O4Magnetic Nano
Particle is dissolved in 30 mL pH=7.4, and concentration is in 0.01mol/L PBS cushioning liquid, leads to nitrogen deoxidation, clear using ultrasonic wave
Magnetic particle is uniformly dispersed by washing machine, obtains finely dispersed Fe3O4Nanoparticles solution；It is molten to weigh 0.2 g carboxymethyl chitosans
In the PBS cushioning liquid of 20 mL pH=7.4, while 0.1 g 1- ethyls of addition-（3- dimethylaminopropyls）Carbodiimide
Hydrochloride（EDAC）Activate the group on carboxymethyl chitosan surface；Carboxymethyl chitosan solution is added into Fe afterwards3O4Nano particle
Solution, 25 DEG C of 2 h of vibration in thermostatic control oscillator vibration, reaction with magnet collect product after terminating, then successively with distilled water and
PBS (pH=7.4) cushioning liquid fully washs, that is, obtains carboxymethyl chitosan magnetic nanocomposites.
1.4 prepare magnetic fluorescence composite Nano pharmaceutical carrier using ionic cross-linking.Take the aqueous phase of the concentration of 1.1 preparations
CdTe quantum, be dissolved in 5mL distilled water after isopropanol separating-purifying, and add sodium polyphosphate, wherein sodium polyphosphate and
The concentration of CdTe quantum is respectively 1 mg/mL and 0.04 mol/L, obtains reaction solution A；By 20 mg hydrophobic drug 5- fluorine
The methanol solution of uracil mixes with 2g carboxymethyl-beta-cyclodextrins, the h of oscillating reactions 2 under normal temperature, obtains including 5 FU 5 fluorouracil
Inclusion compound B；The magnetic nanocomposites for taking the carboxymethyl chitosan prepared in 0.01g steps 1.3 sugar-modified are dissolved in 10 mL distillations
In water, 30 min of ultrasound, magnetic nanometer particles are made to be uniformly dispersed, and it is 1 mg/mL PDDA to add mass concentration, is reacted
Solution C；A and B solution are added dropwise in C solution, 4h is vibrated in 25 DEG C of thermostatic control oscillator vibration, magnet collects reaction production
Thing, reaction product is cleaned with distilled water, produce magnetic fluorescence composite Nano pharmaceutical carrier.Fig. 1 is that the magnetic fluorescence prepared is compound
The abosrption spectrogram of nano-medicament carrier insoluble drug release, Fig. 2 are that the TEM of the magnetic fluorescence composite Nano pharmaceutical carrier prepared shines
Piece.
Embodiment 2：
2.1 prepare CdTe/ZnS quantum dots using Aqueous phase prepares CdTe quantum using chemical coprecipitation first,
For preparation method as described in above-mentioned embodiment 1, it is 4h in the reaction time that difference, which is,.The CdTe quantum prepared is taken to be dissolved in 30
In mL distilled water, wherein the concentration of CdTe quantum is 1.67 × 10-3Mol/L, add 0.0329 g Zn (Ac)2、0.0921
G reductive glutathiones, it is that 1 mol/L NaOH solutions regulation pH value is 8 with the concentration configured, under magnetic stirring, oil bath
100 DEG C are flowed back, and being put into refrigerator after 2 h of magnetic agitation reaction is quickly cooled to room temperature, obtains the CdTe/ of water-soluble high-luminous-efficiency
ZnS quantum dot.
2.2 prepare Fe using hydro-thermal method3O4Nano particle.Take 2.78 g FeSO4·7H2O、4.32 g FeCl3·6H2O
It is dissolved in 30 mL distilled water, after magnetic agitation dissolving, adds 30 mL ethylene glycol, after stirring under nitrogen protection, add
Enter in there-necked flask, adjust pH to 9-11 with the NaOH solution that the concentration configured is 2 mol/L, add surfactant polyethylene
The g of pyrrolidones 0.15, reacts 30 min after being sufficiently stirred, Fe is made3O4The presoma of magnetic nanoparticle.By Fe3O4Magnetic
The presoma of nano particle is transferred in hydrothermal reaction kettle, reacts 6h at 160 DEG C.By resulting solution water and nothing after the completion of reaction
Water-ethanol alternately washs, vacuum dried, obtains dry Fe3O4Magnetic nanoparticle.
2.3 prepare carboxymethyl-beta-cyclodextrin magnetic nanocomposites using blending investment.Weigh 0.2 g Fe3O4Magnetic
Nano particle is dissolved in 30 mL pH=7.4, and concentration is in 0.01mol/L PBS cushioning liquid, leads to nitrogen deoxidation, utilizes ultrasound
Magnetic particle is uniformly dispersed by ripple cleaning machine, obtains finely dispersed Fe3O4Nanoparticles solution；Weigh 0.5 g carboxymethyls-β-
Cyclodextrin is dissolved in the PBS cushioning liquid of 20 mL pH=7.4, while 0.3 g 1- ethyls of addition-（3- dimethylaminos third
Base）Carbodiimide hydrochloride（EDAC）Activate the group on carboxymethyl-beta-cyclodextrin surface；It is afterwards that carboxymethyl-beta-cyclodextrin is molten
Liquid adds Fe3O4Nanoparticles solution, 25 DEG C of 4 h of vibration in thermostatic control oscillator vibration, reaction are collected with magnet after terminating and produced
Thing, then fully washed with distilled water and PBS (pH=7.4) cushioning liquid successively, that is, obtain carboxymethyl-beta-cyclodextrin magnetic Nano
Compound.
2.4 prepare magnetic fluorescence composite Nano pharmaceutical carrier using ionic cross-linking.Take the aqueous phase of the concentration of 2.1 preparations
CdTe/ZnS quantum dots, it is dissolved in 5mL distilled water after isopropanol separating-purifying, and adds sodium tetrapolyphosphate, wherein four polyphosphoric acid
The concentration of sodium and CdTe/ZnS quantum dots is respectively 1.5 mg/mL and 0.05 mol/L, obtains reaction solution A；60mg is hydrophobic
The ethanol solution of property medicine Docetaxel mixes with 4g carboxymethyl-beta-cyclodextrins, the h of oscillating reactions 4 under normal temperature, comprising
The inclusion compound B of Docetaxel；The magnetic Nano for taking the carboxymethyl-beta-cyclodextrin prepared in 0.02 g steps 2.3 to modify is compound
Thing is dissolved in 10 mL distilled water, 30 min of ultrasound, magnetic nanometer particles is uniformly dispersed, and it is 2 mg/mL to add mass concentration
Diallyl dimethyl ammoniumchloride, obtain reaction solution C；A and B solution are added dropwise in C solution, in 25 DEG C of thermostatted water
6h is vibrated in bath oscillator, magnet collecting reaction product, reaction product is cleaned with distilled water, produces magnetic fluorescence composite Nano medicine
Thing carrier.Fig. 3 is the hysteresis curve of the magnetic fluorescence composite Nano pharmaceutical carrier prepared.
Embodiment 3：
The preparation of 3.1 ZnSe/ZnS quantum dot solutions.ZnSe quantum dots are prepared using chemical coprecipitation first, in nitrogen
Under gas shielded, by 0.01g NaBH4It is dissolved in 0.0061g Se powder in 2 mL distilled water, is heated to 40 DEG C, after being completely dissolved
To NaHSe solution；Take 0.0439 g Zn (Ac)2Dissolve in 20 mL distilled water, reduced form paddy Guang is added after it is completely dissolved
Sweet peptide 0.0737g, pH=11.5 are adjusted with 1mol/L NaOH solution, obtain Zn precursor solution；Zn presoma is transferred to
In there-necked flask, injection NaHSe solution, 100 DEG C of oil bath flow back rapidly under nitrogen protection, are taken out after magnetic agitation 1h and are put into refrigerator
In be quickly cooled to room temperature, obtain colourless transparent solution, the ZnSe QDs solution as prepared.Take the ZnSe quantum prepared
15 mL of point, the wherein concentration of ZnSe quantum dots are 2.7 × 10-3Mol/L, add 0.0138 g Zn (Ac)2, 0.0277 g also
Originality glutathione and 0.01 g thiocarbamides, it is that 1 mol/L NaOH solutions regulation pH value is 10.5 with the concentration configured, in magnetic
Under power stirring, 100 DEG C of oil bath flows back, and being put into refrigerator after 2 h of magnetic agitation reaction is quickly cooled to room temperature, obtains faint yellow water-soluble
The ZnSe/ZnS quantum dots of property high-luminous-efficiency.
The preparation of 3.2 magnetic nanoparticles.Patent publication No. is used to prepare Fe for CN101597495A method3O4/CoO
Core-shell structure magnetic nano particle.
3.3 prepare carboxymethyl chitosan magnetic nanocomposites using blending investment.Weigh 0.35 g Fe3O4/ CoO magnetic
Property nano particle be dissolved in 30 mL pH=7.4, concentration is in 0.01mol/L PBS cushioning liquid, leads to nitrogen deoxidation, using super
Magnetic particle is uniformly dispersed by sound wave cleaning machine, obtains finely dispersed Fe3O4/ CoO nanoparticles solutions；Weigh 0.65 g carboxylics
Methyl chitosan is dissolved in the PBS cushioning liquid of 20 mL pH=7.4, while 0.3 g 1- ethyls of addition-（3- dimethylaminos
Propyl group）Carbodiimide hydrochloride（EDAC）Activate the group on carboxymethyl chitosan surface；Carboxymethyl chitosan solution is added afterwards
Enter Fe3O4/ CoO nanoparticles solutions, 25 DEG C of 5 h of vibration in thermostatic control oscillator vibration, reaction are collected with magnet after terminating and produced
Thing, then fully washed with distilled water and PBS (pH=7.4) cushioning liquid successively, that is, obtain carboxymethyl chitosan magnetic Nano and answer
Compound.
3.4 prepare magnetic fluorescence composite nanometer particle using ionic cross-linking.Take the aqueous phase ZnSe/ of the concentration of 3.1 preparations
ZnS quantum dot, it is dissolved in 5mL distilled water after isopropanol separating-purifying, and adds sodium pyrophosphate, wherein sodium pyrophosphate and ZnSe/
The concentration of ZnS quantum dot is respectively 2 mg/mL and 0.1 mol/L, obtains reaction solution A；By 30 mg hydrophobic drug taxols
Ethanol solution mixed with 1.42g Sulfobutyl ether β _ cyclodextrins, obtain including the inclusion compound B of taxol；Take 0.035 g steps 3.3
The magnetic nanocomposites that the carboxymethyl chitosan of middle preparation is sugar-modified are dissolved in 10 mL distilled water, 30 min of ultrasound, magnetic is received
Rice particulate is uniformly dispersed, and it is 2 mg/mL diallyl dimethyl ammoniumchlorides to add mass concentration, obtains reaction solution C；Will
A and B solution are added dropwise in C solution, and 6h, magnet collecting reaction product, with steaming are vibrated in 25 DEG C of thermostatic control oscillator vibration
Distilled water cleans reaction product, produces magnetic fluorescence composite Nano pharmaceutical carrier.Fig. 4 is the magnetic fluorescence composite Nano medicine prepared
The Absorption and fluorescence spectrum of carrier.
Embodiment 4：
4.1 prepare CdSe quantum dot under nitrogen protection using Aqueous phase, by 0.0106 g NaBH4With 0.0063 g
Se powder is dissolved in 2 mL distilled water, is heated to 40 DEG C, and NaHSe solution is obtained after being completely dissolved；Take 0.0533 g Cd (Ac)2It is molten
Enter in 20 mL distilled water, 1.0 mmol mercaptopropionic acids added after it is completely dissolved, with 1mol/L NaOH solution adjust pH=
11.5, obtain Cd precursor solution；Cd presoma is transferred in there-necked flask, injection NaHSe is molten rapidly under nitrogen protection
Liquid, 100 DEG C of oil bath flow back, and are taken out after magnetic agitation 1h and are put into refrigerator the CdSe for being quickly cooled to room temperature, as preparing
QDs solution.
The preparation of 4.2 magnetic nanoparticles.Patent publication No. is used to prepare α-Fe for the A of CN 101928043 method2O3
Magnetic nanoparticle.
4.3 prepare carboxymethyl-beta-cyclodextrin magnetic nanocomposites using blending investment.Weigh 0.5 g α-Fe2O3Magnetic
Property nano particle be dissolved in 30 mL pH=7.4, concentration is in 0.01mol/L PBS cushioning liquid, leads to nitrogen deoxidation, using super
Magnetic particle is uniformly dispersed by sound wave cleaning machine, obtains finely dispersed α-Fe2O3Nanoparticles solution；Weigh 0.8 g carboxylic first
Group-beta-cyclodextrin is dissolved in the cushioning liquid of 20 mL PBS=7.4, while 0.5 g 1- ethyls of addition-（3- dimethylaminos third
Base）Carbodiimide hydrochloride（EDAC）Activate the group on carboxymethyl-beta-cyclodextrin surface；It is afterwards that carboxymethyl-beta-cyclodextrin is molten
Liquid adds α-Fe2O3Nanoparticles solution, 25 DEG C of 6 h of vibration in thermostatic control oscillator vibration, reaction are collected with magnet after terminating and produced
Thing, then fully washed with distilled water and PBS (pH=7.4) cushioning liquid successively, that is, obtain carboxymethyl-beta-cyclodextrin magnetic Nano
Compound.
4.4 prepare magnetic fluorescence composite Nano pharmaceutical carrier using ionic cross-linking.Take the aqueous phase of the concentration of 4.1 preparations
CdSe quantum dot, it is dissolved in 5 mL distilled water after isopropanol separating-purifying, and adds sodium molybdate, wherein sodium molybdate and CdSe quantum
The concentration of point is respectively 2.5 mg/mL and 0.25 mol/L, obtains reaction solution A；By the first of 50mg hydrophobic drug camptothecines
Alcoholic solution mixes with 3.9g Sulfobutyl ether β _ cyclodextrins, obtains including the inclusion compound B of camptothecine；Take in 0.05 g steps 4.3 and prepare
Carboxymethyl-beta-cyclodextrin modification magnetic nanocomposites be dissolved in 10 mL distilled water, 30 min of ultrasound, make magnetic Nano
Particulate is uniformly dispersed, and it is 5 mg/mL diallyl dimethyl ammoniumchlorides to add mass concentration, obtains reaction solution C；By A
It is added dropwise with B solution in C solution, 10 h, magnet collecting reaction product, with steaming is vibrated in 25 DEG C of thermostatic control oscillator vibration
Distilled water cleans reaction product, produces magnetic fluorescence composite Nano pharmaceutical carrier.Fig. 5 is the magnetic fluorescence composite Nano medicine prepared
Digital photograph of the carrier in uviol lamp and externally-applied magnetic field.
Claims (6)
- A kind of 1. preparation method of magnetic fluorescence composite Nano pharmaceutical carrier, it is characterised in that：With negatively charged carboxymethyl shell Glycan or magnetic nanoparticle, diallyl dimethyl ammoniumchloride (PDDA), the ionomer of carboxymethyl-beta-cyclodextrin modification Agent connects water-soluble quantum dot by ionic cross-linking with the anionic macromolecule organic of carrying medicament and obtained, described water-soluble Property quantum dot is evenly distributed on the surface of magnetic nanoparticle in the form of single dispersing, and the particle size of wherein magnetic nanoparticle exists 10-200nm, the particle diameter of quantum dot is in 1.5-10nm；Described preparation method comprises the following steps that：(a) negatively charged magnetic nanocomposites are prepared using blending investment：1. weigh 50-500mg magnetic nanoparticles 30mL pH=7.4 are dissolved in, concentration is in 0.01mol/L PBS cushioning liquid, leads to nitrogen deoxidation, will using supersonic wave cleaning machine Magnetic nanoparticle is uniformly dispersed；2. weigh 10-800mg carboxymethyl chitosans or carboxymethyl-beta-cyclodextrin is dissolved in 20mL pH= In 7.4 PBS cushioning liquid, while add 0.1-0.5g 1- ethyls-(3- dimethylaminopropyls) carbodiimide hydrochloride (EDAC) carboxymethyl chitosan or the group on carboxymethyl-beta-cyclodextrin surface are activated；1. and 2. 3. two solution will mix, in constant temperature 25 DEG C of vibration 2-6h in water bath chader, then fully washed with distilled water and pH=7.4 PBS cushioning liquid successively, that is, obtain Negatively charged magnetic nanocomposites；(b) magnetic fluorescence composite Nano pharmaceutical carrier is prepared using ionic cross-linking：Take the aqueous phase quantum point of the concentration of preparation to be dissolved in distilled water, and add ion crosslinking agent, obtain reaction solution A；It will dredge The methanol or ethanol solution of aqueous pharmaceutical mix with anionic macromolecule organic, oscillating reactions 2-10h under normal temperature, are wrapped The inclusion compound B of drug containing；The negatively charged magnetic nanocomposites prepared in 0.005-0.05g steps (a) are taken to be dissolved in distillation In water, ultrasonic 20-60min, magnetic nanocomposites is uniformly dispersed, and add diallyl dimethyl ammoniumchloride and obtain instead Answer solution C；Reaction solution A and B are added dropwise in reaction solution C, oscillating reactions 2-10h under normal temperature, centrifuged, distillation Water washing, that is, obtain magnetic fluorescence composite Nano pharmaceutical carrier；Described ion crosslinking agent is selected from tripolyphosphate, four Quadrafos, hexametaphosphate, pyrophosphate, molybdate, transparent One or more in matter acid or gamma-polyglutamic acid；Anionic macromolecule organic is selected from carboxymethyl-beta-cyclodextrin or sulphur fourth Group-beta-cyclodextrin；Described carboxymethyl chitosan selects O-CMC or N, O-CMC；Polydiene propyl group The molecular weight and mass concentration of alkyl dimethyl ammonium chloride are respectively 1 × 105-2×105And 0.51-5.1mg/mL；The thickness of carboxymethyl chitosan or carboxymethyl-beta-cyclodextrin on magnetic nanoparticle surface is 3-10nm in step (a)；Step Suddenly the mol ratio of hydrophobic drug and anionic macromolecule organic is 1 in (b):10-1:60, negatively charged magnetic Nano The mol ratio of compound and quantum dot is 1:1-1:20, diallyl dimethyl ammoniumchloride：Anionic macromolecule organic： The mass ratio of ion crosslinking agent is 1:0.1-2:0.01-0.5.
- A kind of 2. preparation method of magnetic fluorescence composite Nano pharmaceutical carrier according to claim 1, it is characterised in that institute The particle diameter for the magnetic fluorescence composite Nano pharmaceutical carrier stated is 10-220nm；Described magnetic nanoparticle (MNPs) is selected from Fe3O4、Fe2O3、MeFe2O4, compound neodymium iron boron, SmCo, wherein Me=Co, Mn, Ni；The preparation method of magnetic nanoparticle is Coprecipitation or hydro-thermal method；Contain at least one of hydroxyl, amino, carboxyl in magnetic nanoparticle surface.
- A kind of 3. preparation method of magnetic fluorescence composite Nano pharmaceutical carrier according to claim 1, it is characterised in that institute The quantum dot stated is the water-soluble quantum dot that surface carries hydrophilic radical, and quantum dot is Group II-VI semiconductor material, Huo Zhewei The composite that II-VI semiconductor material is formed.
- A kind of 4. preparation method of magnetic fluorescence composite Nano pharmaceutical carrier according to claim 1, it is characterised in that institute The hydrophobic drug stated is selected from least one of brufen, 5 FU 5 fluorouracil, Docetaxel, camptothecine or taxol.
- 5. the preparation method of magnetic fluorescence composite Nano pharmaceutical carrier according to claim 3, it is characterized in that：The quantum Contain at least one of sulfydryl, carboxyl, amino in point surface；Hydrophilic radical part used in quantum dot synthesis is selected from 3- mercaptos Base propionic acid, TGA, Cys, 2 mercaptopropionic acid, mercaptobutyric acid, mercaptopentanoic acid, mercaptohexanoic acid, dimercaptosuccinic acid, One or more in mercaptoethanol, glutathione, mercaprol or mercaptoethylmaine.
- A kind of 6. preparation method of magnetic fluorescence composite Nano pharmaceutical carrier according to claim 3, it is characterised in that institute It is 1.5-10nm to state quantum point grain diameter；Quantum dot be ZnSe, CdSe, CdTe, CdS, ZnSe/ZnS, CdS/ZnS, CdSe/ZnS, CdTe/ZnS、ZnXCd1-XSe、CdSe1-XSX、CdSe1-XTeX、CdSe/ZnSe、CdS/ZnSe、CdTe/ZnSe、CdSe/CdS、 CdTe/CdS、CdS/ZnXCd1-XS、ZnSe/ZnXCd1-XS、CdSe/ZnXCd1-XS or CdTe/ZnXCd1-XOne kind in S, wherein 0 ＜ X ＜ 1.
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| CN106565024B (en) * | 2016-11-04 | 2020-04-07 | 长江大学 | Scale inhibitor for oil-gas field produced water and preparation method thereof |
| TWI753119B (en) * | 2017-03-17 | 2022-01-21 | 南韓商東友精細化工有限公司 | Quantum dot having organic ligand and use thereof |
| CN107224753B (en) * | 2017-07-17 | 2019-07-23 | 江苏理工学院 | A method of utilizing Magnetic solid phases extraction adsorbent material enrichment detection camptothecine |
| CN107551275B (en) * | 2017-09-12 | 2020-06-12 | 山西大学 | Preparation of magnetic nano-drug carrier and method for loading doxorubicin hydrochloride by using magnetic nano-drug carrier |
| CN109091678B (en) * | 2018-08-21 | 2022-01-28 | 南开大学 | Preparation method and application of double-regulation supermolecule assembly for inhibiting tumor invasion and diffusion |
| CN110101871B (en) * | 2019-05-30 | 2022-03-25 | 广东工业大学 | Preparation method of embedded resveratrol |
| CN111468050A (en) * | 2020-04-29 | 2020-07-31 | 福州大学 | Method for preparing composite essential oil particles based on microfluidic technology |
| CN112779000B (en) * | 2021-01-20 | 2023-09-15 | 南京邮电大学 | Quantum dot modified by quaternized polydentate ligand, and preparation method and application thereof |
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Non-Patent Citations (2)
| Title |
|---|
| Multi-Shell Structured Fluorescent-Magnetic Nanoprobe for Target Cell Imaging and On-Chip Sorting;Peng-Hui Zhang et al.;《ACS Appl. Mater. Interfaces》;20130703;第1-27页 * |
| 磁性荧光复合纳米材料的研究进展;闫君等;《现代陶瓷技术》;20150228(第1期);第18-25页 * |
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