CN103550162A - Preparation method of targeted ferroferric oxide-porphyrin containing composite nanoparticles - Google Patents
Preparation method of targeted ferroferric oxide-porphyrin containing composite nanoparticles Download PDFInfo
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Abstract
The invention discloses a preparation method of targeted ferroferric oxide-porphyrin containing composite nanoparticles, and relates to a preparation method of composite nanoparticles. The preparation method disclosed by the invention aims at solving the problems that a photosensitizer is high in accumulation effect within normal tissues and even performs a photochemical reaction under a dark light because a photosensitizer fluorescence signal is low in intensity and low in selective uptake for tumour tissues, existing in photodynamic diagnosis and therapy. The method comprises the following steps: 1, preparing magnetic ferroferric oxide nanoparticles coated by silicon dioxide; 2, preparing a porphyrin compound; 3, preparing a porphyrin compound bound by a silane reagent; 4, preparing a porphyrin-folic acid compound; and 5, preparing the targeted ferroferric oxide-porphyrin containing composite nanoparticles. The preparation method based on the magnetic ferroferric oxide-porphyrin composite nanoparticles and disclosed by the invention integrates magnetofluid thermal therapy, magnetic targeting and photodynamic therapy as a therapy means for tumours. The preparation method disclosed by the invention is used for preparing the targeted ferroferric oxide-porphyrin containing composite nanoparticles.
Description
Technical field
The present invention relates to the preparation method of composite nanoparticle.
Background technology
Tumor thermotherapy has become " green remedy " of a kind of brand-new treatment tumor after operation, radiotherapy, chemotherapy.Thermotherapy not only has direct cellulotoxic effect to tumor cell, can also use with chemotherapy, chemotherapy combined radiotherapy, can strengthen the curative effect of chemotherapy, radiotherapy, improves the immunity of body, suppresses the transfer of tumor.Yet conventional thermotherapy method is because of its targeting ability to tumor, easily cause the temperature for the treatment of region surrounding tissue raise and produce damage, in clinical practice, be restricted, development along with nanotechnology, German scholar Jordan proposes a kind of new heating therapy-nanometer magnetofluid thermotherapy (magnetic fluid hyperthermia, MFH) treatment tumor has obtained impressive progress, and the advantage of the method is exactly to heat up in targeting location, injury-free without organizing of magnetic particle; Another fermentation, the magnetic targeting of magnetic nano-particle can be accumulated in lesions position in surperficial Porphyrin-Based Sensitizer by binding, thereby improves Porphyrin-Based Sensitizer in the accumulative effect of lesions position.Photodynamics Clinics and Practices be utilize some photosensitive drugs can priority enrichment in tumor locus, by the rayed photosensitive drug of suitable wavelength, utilize the photodynamic reaction of photosensitive drug tumor is diagnosed and treated.By detecting the fluorescence of photosensitizer generation, can detect early cancer or the precancerous lesion that naked eyes cannot observe, have noinvasive, quick, objective, the feature such as can record, can repeat, and can be by the infiltration degree of characteristic fluorescence indication tumor, carry out the level diagnosis of tumor, make the treatment of tumor more thorough.Photodynamic therapy is a kind of tumor therapeuticing method of Wicresoft, have that antitumor spectra is wide, indication is wide, repeatedly repetitive therapy, can selective killing tumor cell, retain to large extent the function of normal organ and tissue; Combining with chemotherapy and radiation to use has certain synergism, photodynamic therapy to combine use with operation, the advantages such as energy Reduction surgery scope and minimizing postoperative recurrence.Yet also there are some shortcomings in photodynamics Clinics and Practices at present.Such as: (1) prominent question is exactly that photosensitizer fluorescence signal intensity is not strong; (2) picked-up of the selectivity of tumor tissues is not high, causes the existence of photosensitizer in other normal structures such as skin, and photochemical reaction even also occurs under half-light; (3) photosensitive drug is generally porphyrin derivant, and most of water solublity are bad, and after intravenous injection, the fluctuation of blood Chinese medicine concentration is usually inevitable.Therefore, can only administration within the time limiting, and dosage is limited, is difficult to the curative effect that reaches satisfied.
Summary of the invention
The present invention will solve photodynamics Clinics and Practices and exist photosensitizer fluorescence signal intensity not strong, the selectivity picked-up of tumor tissues is not high, cause the accumulative effect of photosensitizer in other normal structures such as skin high, even under half-light, also there is the problem of photochemical reaction, and the preparation method with targeting ferroso-ferric oxide-porphyrin composite nanoparticle providing.
There is the preparation method of targeting ferroso-ferric oxide-porphyrin composite nanoparticle, specifically according to following steps, carry out:
One, adopt FeCl
36H
2o compound concentration is the FeCl of 0.1mol/L
3solution, adopts FeSO
44H
2o compound concentration is the FeSO of 0.1mol/L
4solution;
Under nitrogen protection and mechanical agitation condition, according to Fe
3+with Fe
2+mol ratio is 2:1, the FeCl that is 0.1mol/L by 100mL concentration
3the FeSO that solution and 50mL concentration are 0.1mol/L
4solution mixes, and obtains FeCl
3and FeSO
4mixed solution, then to adopt concentration be that the salt acid for adjusting pH value of 1mol/L is 5, then adding mass concentration is 25% ammonia spirit, until black precipitate appears in mixed solution, then continues to stir 1h, obtains solid-liquid mixed liquor;
Under additional the action of a magnetic field, the upper strata waste liquid of solid-liquid mixed liquor is inclined, then use deionized water rinsing precipitate, obtain Fe
3o
4magnetic nano-particle; By Fe
3o
4magnetic nano-particle is dispersed in the NaCl aqueous solution that concentration is 0.4mol/L to Fe
3o
4the concentration of magnetic nano-particle is 7.5mg/mL, obtain mixed liquid A, then getting the mixed liquid A of 10mL adds 30mL to be dissolved with in the alcoholic solution of 1.5mL tetraethoxysilane, then add successively the ammonia that 30mL deionized water, 30mL dehydrated alcohol and 2.5mL mass concentration are 28%, continue again to stir 90min, then by magnetic separation, remove the upper strata stillness of night, then wash magnetic nano-particle 3 times with redistilled water and alcohol mixeding liquid, obtain the magnetic ferroferric oxide nano-particles of coated with silica;
Two, by 150mg tetrahydroxy phenyl porphyrin compound, 2g Anhydrous potassium carbonate and 40mLN, dinethylformamide mixes, the magnetic stirrer 10 minutes of brine ice is equipped with in utilization, then the chloracetyl chloride that adds 1.5mL, under cryosel bath condition, continue reaction 4.5h, add again 90mL～110mL redistilled water, then with 100mL dichloromethane, extract, take off a layer solution;
By the solution anhydrous sodium sulfate drying 24h of gained lower floor, use again Rotary Evaporators solvent evaporated, obtain the different porphyrin compound mixture that chloracetyl chloride replaces, then adopt silica gel column chromatography to carry out separation, take pure dichloromethane as eluent, obtain the compound of the first chromatographic band, dichloromethane and the methanol mixed solution that dichloromethane and methanol volume ratio be 100:1 of take is again eluent, obtain the compound of the second chromatographic band, then dichloromethane and the methanol mixed eluent that dichloromethane and methanol volume ratio be 100:1.5 of take is eluant, obtain the compound of tertiary color bands of a spectrum, dichloromethane and the methanol mixed eluent that dichloromethane and methanol volume ratio be 100:1.8 of take is again eluant, obtain the compound of the 4th chromatographic band, . dichloromethane and the methanol mixed eluent that dichloromethane and methanol volume ratio be 100:2.5 of take is again eluant, obtain the compound 1 of multicolored bands of a spectrum, wherein, the structural formula of compound 1 is
Three, the compound 1 100mg step 2 being obtained, 2g Anhydrous potassium carbonate, 1.5mL chloropropyl triethoxysilane and 20mL oxolane mix, at lucifuge condition lower magnetic force, stir 20h～28h, refilter, then unreacted silane reagent and oxolane are removed in distilling under reduced pressure, obtain crude product siloxanes porphyrin; Then take silica gel as immobile phase, the dichloromethane that dichloromethane and methanol volume ratio are 1:5 and the mixed solution of methanol carry out drip washing as eluant, collect the compound of the first chromatographic band, obtain the porphyrin compound of silane reagent binding, the structural formula of this porphyrin compound is
Four, the porphyrin compound at ambient temperature 50mg step 3 being obtained and 4g anhydrous K
2cO
3be dissolved in 30mLDMSO, add again 40mg folic acid, at room temperature lucifuge condition lower magnetic force, stir 10h, the freezing ether that adds again 300mL, then in temperature, be sucking filtration under-15 ℃～-22 ℃ conditions, obtain aubergine solid, then to adopt temperature be the ice ether washing of-20 ℃, obtain the porphyrin-folic acid compound of folic acid binding, the structural formula of this porphyrin-folic acid compound is
In the mixed solvent of the magnetic ferroferric oxide nano-particles of the coated with silica five, step 1 being obtained by the ultrasonic 30mL of being distributed to alcohol and 30mL deionized water, controlling temperature is 60 ℃, under mechanical agitation condition, porphyrin-the folic acid compound that adds 20mg step 4 to obtain, then controlling temperature is 60 ℃ of reaction 2h, separated by magnetic again, obtain having targeting ferroso-ferric oxide-porphyrin composite nanoparticle.
The present invention utilizes silane coupler, makes the porphyrin compound with targeting firmly be bonded in magnetic nano particle sub-surface;
The present invention utilizes chloracetyl chloride as connecting base, can more accurately determine the number of binding targeted molecular folic acid;
The present invention is in view of first using coated with silica magnetic nano-particle, then at its surface bonded porphyrin photosensitive molecular, thereby can effectively avoid influencing each other between optomagnetic.
Targeting ferroso-ferric oxide composite nanoparticle prepared by the present invention has initiatively property and the two targeting character of physics magnetic targeting.
The invention has the beneficial effects as follows:
(1) based on magnetic ferroferric oxide porphyrin composite nanoparticle, have and integrate Magnetic Fluid Hyperthermia and photodynamic therapy as the treatment means of tumor, and on nanometer level, prepare the composite that fluorescent nano particles and magnetic Nano material connect by chemical bond;
(2) magnetic nano-particle not only can be used as Magnetic Fluid Hyperthermia " hot seed " material, can also pass through the finishing to magnetic nano-particle, it is connected, with photosensitizer by chemical bond in oncotherapy, by externally-applied magnetic field mediation, carry photosensitive drug and enter tumor tissues; The chemical sensitization effect of thermotherapy can promote the absorption of tumor cell to photosensitizer, thereby improves the photosensitizer concentration ratio of tumor tissues/normal structure;
(3) by the active targeting of surface bonded folic acid, and the magnetic targeting effect of ferriferrous oxide nano-particle, can greatly reduce the disperse of porphyrin compound in normal structure, thereby the phototoxicity of porphyrin compound will reduce greatly, make diagnosis and treatment not cause the photochemical damage of normal structure; There is strong, stable fluorescence output, the position of diagnosing tumour that can be sensitive; And Magnetic Fluid Hyperthermia can suppress the transfer of tumor, improve the immunocompetence of body, so the two combination, can play synergism, bring out one's strengths to make up for one's weaknesses.And there is ferromagnetic optomagnetic one nanoparticle, reach Magnetic Fluid Hyperthermia and photodynamics Clinics and Practices are organically combined.
The present invention is for the preparation of having targeting ferroso-ferric oxide-porphyrin composite nanoparticle.
Accompanying drawing explanation
Fig. 1 is the uv absorption spectra of the compound 1 that obtains of embodiment mono-step 2; Fig. 2 is mass spectrum;
Fig. 3 is the uv absorption spectra of the porphyrin-folic acid compound of the folic acid binding that obtains of embodiment mono-step 4; Fig. 4 is mass spectrum;
Fig. 5 is the fluorescence spectrum figure with targeting ferroso-ferric oxide-porphyrin composite nanoparticle that embodiment mono-step 5 obtains; Fig. 6 is scanning electron microscope (SEM) photograph.
The specific embodiment
Technical solution of the present invention is not limited to the following cited specific embodiment, also comprises the combination in any between each specific embodiment.
The specific embodiment one: present embodiment has the preparation method of targeting ferroso-ferric oxide-porphyrin composite nanoparticle, specifically carries out according to following steps:
One, adopt FeCl
36H
2o compound concentration is the FeCl of 0.1mol/L
3solution, adopts FeSO
44H
2o compound concentration is the FeSO of 0.1mol/L
4solution;
Under nitrogen protection and mechanical agitation condition, according to Fe
3+with Fe
2+mol ratio is 2:1, the FeCl that is 0.1mol/L by 100mL concentration
3the FeSO that solution and 50mL concentration are 0.1mol/L
4solution mixes, and obtains FeCl
3and FeSO
4mixed solution, then to adopt concentration be that the salt acid for adjusting pH value of 1mol/L is 5, then adding mass concentration is 25% ammonia spirit, until black precipitate appears in mixed solution, then continues to stir 1h, obtains solid-liquid mixed liquor;
Under additional the action of a magnetic field, the upper strata waste liquid of solid-liquid mixed liquor is inclined, then use deionized water rinsing precipitate, obtain Fe
3o
4magnetic nano-particle; By Fe
3o
4magnetic nano-particle is dispersed in the NaCl aqueous solution that concentration is 0.4mol/L to Fe
3o
4the concentration of magnetic nano-particle is 7.5mg/mL, obtain mixed liquid A, then getting the mixed liquid A of 10mL adds 30mL to be dissolved with in the alcoholic solution of 1.5mL tetraethoxysilane, then add successively the ammonia that 30mL deionized water, 30mL dehydrated alcohol and 2.5mL mass concentration are 28%, continue again to stir 90min, then by magnetic separation, remove the upper strata stillness of night, then wash magnetic nano-particle 3 times with redistilled water and alcohol mixeding liquid, obtain the magnetic ferroferric oxide nano-particles of coated with silica;
Two, by 150mg tetrahydroxy phenyl porphyrin compound, 2g Anhydrous potassium carbonate and 40mLN, dinethylformamide mixes, the magnetic stirrer 10 minutes of brine ice is equipped with in utilization, then the chloracetyl chloride that adds 1.5mL, under cryosel bath condition, continue reaction 4.5h, add again 90mL～110mL redistilled water, then with 100mL dichloromethane, extract, take off a layer solution;
By the solution anhydrous sodium sulfate drying 24h of gained lower floor, use again Rotary Evaporators solvent evaporated, obtain the different porphyrin compound mixture that chloracetyl chloride replaces, then adopt silica gel column chromatography to carry out separation, take pure dichloromethane as eluent, obtain the compound of the first chromatographic band, dichloromethane and the methanol mixed solution that dichloromethane and methanol volume ratio be 100:1 of take is again eluent, obtain the compound of the second chromatographic band, then dichloromethane and the methanol mixed eluent that dichloromethane and methanol volume ratio be 100:1.5 of take is eluant, obtain the compound of tertiary color bands of a spectrum, dichloromethane and the methanol mixed eluent that dichloromethane and methanol volume ratio be 100:1.8 of take is again eluant, obtain the compound of the 4th chromatographic band, . dichloromethane and the methanol mixed eluent that dichloromethane and methanol volume ratio be 100:2.5 of take is again eluant, obtain the compound 1 of multicolored bands of a spectrum, wherein, the structural formula of compound 1 is
Three, the compound 1 100mg step 2 being obtained, 2g Anhydrous potassium carbonate, 1.5mL chloropropyl triethoxysilane and 20mL oxolane mix, at lucifuge condition lower magnetic force, stir 20h～28h, refilter, then unreacted silane reagent and oxolane are removed in distilling under reduced pressure, obtain crude product siloxanes porphyrin; Then take silica gel as immobile phase, the dichloromethane that dichloromethane and methanol volume ratio are 1:5 and the mixed solution of methanol carry out drip washing as eluant, collect the compound of the first chromatographic band, obtain the porphyrin compound of silane reagent binding, the structural formula of this porphyrin compound is
Four, the porphyrin compound at ambient temperature 50mg step 3 being obtained and 4g anhydrous K
2cO
3be dissolved in 30mLDMSO, add again 40mg folic acid, at room temperature lucifuge condition lower magnetic force, stir 10h, the freezing ether that adds again 300mL, then in temperature, be sucking filtration under-15 ℃～-22 ℃ conditions, obtain aubergine solid, then to adopt temperature be the ice ether washing of-20 ℃, obtain the porphyrin-folic acid compound of folic acid binding, the structural formula of this porphyrin-folic acid compound is
In the mixed solvent of the magnetic ferroferric oxide nano-particles of the coated with silica five, step 1 being obtained by the ultrasonic 30mL of being distributed to alcohol and 30mL deionized water, controlling temperature is 60 ℃, under mechanical agitation condition, porphyrin-the folic acid compound that adds 20mg step 4 to obtain, then controlling temperature is 60 ℃ of reaction 2h, separated by magnetic again, obtain having targeting ferroso-ferric oxide-porphyrin composite nanoparticle.
The specific embodiment two: present embodiment is different from the specific embodiment one: the redistilled water that the volume ratio that adopts redistilled water and ethanol in step 1 is 1:1 and alcohol mixeding liquid washing.Other is identical with the specific embodiment one.
The specific embodiment three: present embodiment is different from the specific embodiment one: add 100mL redistilled water in step 2.Other is identical with the specific embodiment one.
The specific embodiment four: present embodiment is different from the specific embodiment one: stir 24h at lucifuge condition lower magnetic force in step 3.Other is identical with the specific embodiment one.
The specific embodiment five: present embodiment is different from the specific embodiment one: be sucking filtration under-20 ℃ of conditions in temperature in step 4.Other is identical with the specific embodiment one.
Adopt following examples to verify beneficial effect of the present invention:
Embodiment mono-:
The present embodiment has the preparation method of targeting ferroso-ferric oxide-porphyrin composite nanoparticle, it is characterized in that having the preparation method of targeting ferroso-ferric oxide-porphyrin composite nanoparticle, specifically according to following steps, carries out:
One, adopt analytical pure FeCl
36H
2o compound concentration is the FeCl of 0.1mol/L
3solution, adopts analytical pure FeSO
44H
2o compound concentration is the FeSO of 0.1mol/L
4solution;
Under nitrogen protection and mechanical agitation condition, according to Fe
3+with Fe
2+mol ratio is 2:1, the FeCl that is 0.1mol/L by 100mL concentration
3the FeSO that solution and 50mL concentration are 0.1mol/L
4solution mixes, and obtains FeCl
3and FeSO
4mixed solution, then to adopt concentration be that the salt acid for adjusting pH value of 1mol/L is 5, then adding mass concentration is 25% ammonia spirit, until black precipitate appears in mixed solution, then continues to stir 1h, obtains solid-liquid mixed liquor;
Under additional the action of a magnetic field, the upper strata waste liquid of solid-liquid mixed liquor is inclined, then use deionized water rinsing precipitate, obtain Fe
3o
4magnetic nano-particle; By Fe
3o
4magnetic nano-particle is dispersed in the NaCl aqueous solution that concentration is 0.4mol/L to Fe
3o
4the concentration of magnetic nano-particle is 7.5mg/mL, obtain mixed liquid A, then getting the mixed liquid A of 10mL adds 30mL to be dissolved with in the alcoholic solution of 1.5mL tetraethoxysilane, then add successively the ammonia that 30mL deionized water, 30mL dehydrated alcohol and 2.5mL mass concentration are 28%, continue again to stir 90min, then by magnetic separation, remove the upper strata stillness of night, then wash magnetic nano-particle 3 times with redistilled water and alcohol mixeding liquid, obtain the magnetic ferroferric oxide nano-particles of coated with silica;
Two, by 150mg tetrahydroxy phenyl porphyrin compound, 2g Anhydrous potassium carbonate and 40mLN, dinethylformamide mixes, be equipped with on the magnetic stirring apparatus of brine ice, stir 10 minutes, then the chloracetyl chloride that adds 1.5mL continues reaction 4.5 hours, then adds 100mL redistilled water under cryosel bath condition, then with 100mL dichloromethane, extract, take off a layer solution;
By the solution anhydrous sodium sulfate drying 24h of gained lower floor, use again Rotary Evaporators solvent evaporated, obtain the different porphyrin compound mixture that chloracetyl chloride replaces, then adopt silica gel column chromatography to carry out separation, take pure dichloromethane as eluent, obtain the compound of the first chromatographic band, dichloromethane and the methanol mixed solution that dichloromethane and methanol volume ratio be 100:1 of take is again eluent, obtain the compound of the second chromatographic band, then dichloromethane and the methanol mixed eluent that dichloromethane and methanol volume ratio be 100:1.5 of take is eluant, dichloromethane and the methanol mixed eluent that dichloromethane and methanol volume ratio be 100:1.8 of take is again eluant, obtain the compound of tertiary color bands of a spectrum, . dichloromethane and the methanol mixed eluent that dichloromethane and methanol volume ratio be 100:2.5 of take is again eluant, obtain the compound of multicolored bands of a spectrum, the structural formula of compound 1 is
Three, the compound 1 100mg step 2 being obtained, 2g Anhydrous potassium carbonate, 1.5mL chloropropyl triethoxysilane and 20mL oxolane mix, at lucifuge condition lower magnetic force, stir 24 hours, refilter, then unreacted silane reagent and oxolane are removed in distilling under reduced pressure, obtain crude product siloxanes porphyrin; Then take silica gel as immobile phase, the dichloromethane that dichloromethane and methanol volume ratio are 1:5 and the mixed solution of methanol carry out drip washing as eluant, collect the compound of the first chromatographic band, obtain the porphyrin compound of silane reagent binding, the structural formula of this porphyrin compound is
Four, the porphyrin compound at ambient temperature 50mg step 3 being obtained and 4g anhydrous K
2cO
3be dissolved in 30mLDMSO, add again 40mg folic acid, at room temperature lucifuge condition lower magnetic force, stir 10h, the freezing ether that adds again 300mL, then sucking filtration under cryogenic conditions, obtains aubergine solid, then to adopt temperature be the ice ether washing of-20 ℃, obtain the porphyrin-folic acid compound of folic acid binding, the structural formula of this porphyrin-folic acid compound is
In the mixed solvent of the magnetic ferroferric oxide nano-particles of the coated with silica five, step 1 being obtained by the ultrasonic 30mL of being distributed to alcohol and 30mL deionized water, controlling temperature is 60 ℃, under mechanical agitation condition, porphyrin-the folic acid compound that adds 20mg step 4 to obtain, then controlling temperature is 60 ℃ of reaction 2h, separated by magnetic again, obtain having targeting ferroso-ferric oxide-porphyrin composite nanoparticle.
The uv absorption spectra of the compound 1 that the present embodiment step 2 obtains as shown in Figure 1; Mass spectrum as shown in Figure 2;
The uv absorption spectra of the porphyrin-folic acid compound of the folic acid binding that step 4 obtains as shown in Figure 3; Mass spectrum as shown in Figure 4;
The fluorescence spectrum figure with targeting ferroso-ferric oxide-porphyrin composite nanoparticle that step 5 obtains as shown in Figure 5; Scanning electron microscope (SEM) photograph as shown in Figure 6.
Claims (5)
1. the preparation method with targeting ferroso-ferric oxide-porphyrin composite nanoparticle, is characterized in that having the preparation method of targeting ferroso-ferric oxide-porphyrin composite nanoparticle, specifically according to following steps, carries out:
One, adopt FeCl
36H
2o compound concentration is the FeCl of 0.1mol/L
3solution, adopts FeSO
44H
2o compound concentration is the FeSO of 0.1mol/L
4solution;
Under nitrogen protection and mechanical agitation condition, according to Fe
3+with Fe
2+mol ratio is 2:1, the FeCl that is 0.1mol/L by 100mL concentration
3the FeSO that solution and 50mL concentration are 0.1mol/L
4solution mixes, and obtains FeCl
3and FeSO
4mixed solution, then to adopt concentration be that the salt acid for adjusting pH value of 1mol/L is 5, then adding mass concentration is 25% ammonia spirit, until black precipitate appears in mixed solution, then continues to stir 1h, obtains solid-liquid mixed liquor;
Under additional the action of a magnetic field, the upper strata waste liquid of solid-liquid mixed liquor is inclined, then use deionized water rinsing precipitate, obtain Fe
3o
4magnetic nano-particle; By Fe
3o
4magnetic nano-particle is dispersed in the NaCl aqueous solution that concentration is 0.4mol/L to Fe
3o
4the concentration of magnetic nano-particle is 7.5mg/mL, obtain mixed liquid A, then getting the mixed liquid A of 10mL adds 30mL to be dissolved with in the alcoholic solution of 1.5mL tetraethoxysilane, then add successively the ammonia that 30mL deionized water, 30mL dehydrated alcohol and 2.5mL mass concentration are 28%, continue again to stir 90min, then by magnetic separation, remove the upper strata stillness of night, then wash magnetic nano-particle 3 times with redistilled water and alcohol mixeding liquid, obtain the magnetic ferroferric oxide nano-particles of coated with silica;
Two, by 150mg tetrahydroxy phenyl porphyrin compound, 2g Anhydrous potassium carbonate and 40mLN, dinethylformamide mixes, the magnetic stirrer 10 minutes of brine ice is equipped with in utilization, then the chloracetyl chloride that adds 1.5mL, under cryosel bath condition, continue reaction 4.5h, add again 90mL～110mL redistilled water, then with 100mL dichloromethane, extract, take off a layer solution;
By the solution anhydrous sodium sulfate drying 24h of gained lower floor, use again Rotary Evaporators solvent evaporated, obtain the different porphyrin compound mixture that chloracetyl chloride replaces, then adopt silica gel column chromatography to carry out separation, take pure dichloromethane as eluent, obtain the compound of the first chromatographic band, dichloromethane and the methanol mixed solution that dichloromethane and methanol volume ratio be 100:1 of take is again eluent, obtain the compound of the second chromatographic band, then dichloromethane and the methanol mixed eluent that dichloromethane and methanol volume ratio be 100:1.5 of take is eluant, obtain the compound of tertiary color bands of a spectrum, dichloromethane and the methanol mixed eluent that dichloromethane and methanol volume ratio be 100:1.8 of take is again eluant, obtain the compound of the 4th chromatographic band, . dichloromethane and the methanol mixed eluent that dichloromethane and methanol volume ratio be 100:2.5 of take is again eluant, obtain the compound 1 of multicolored bands of a spectrum, wherein, the structural formula of compound 1 is
Three, the compound 1 100mg step 2 being obtained, 2g Anhydrous potassium carbonate, 1.5mL chloropropyl triethoxysilane and 20mL oxolane mix, at lucifuge condition lower magnetic force, stir 20h～28h, refilter, then unreacted silane reagent and oxolane are removed in distilling under reduced pressure, obtain crude product siloxanes porphyrin; Then take silica gel as immobile phase, the dichloromethane that dichloromethane and methanol volume ratio are 1:5 and the mixed solution of methanol carry out drip washing as eluant, collect the compound of the first chromatographic band, obtain the porphyrin compound of silane reagent binding, the structural formula of this porphyrin compound is
Four, the porphyrin compound at ambient temperature 50mg step 3 being obtained and 4g anhydrous K
2cO
3be dissolved in 30mLDMSO, add again 40mg folic acid, at room temperature lucifuge condition lower magnetic force, stir 10h, the freezing ether that adds again 300mL, then in temperature, be sucking filtration under-15 ℃～-22 ℃ conditions, obtain aubergine solid, then to adopt temperature be the ice ether washing of-20 ℃, obtain the porphyrin-folic acid compound of folic acid binding, the structural formula of this porphyrin-folic acid compound is
In the mixed solvent of the magnetic ferroferric oxide nano-particles of the coated with silica five, step 1 being obtained by the ultrasonic 30mL of being distributed to alcohol and 30mL deionized water, controlling temperature is 60 ℃, under mechanical agitation condition, porphyrin-the folic acid compound that adds 20mg step 4 to obtain, then controlling temperature is 60 ℃ of reaction 2h, separated by magnetic again, obtain having targeting ferroso-ferric oxide-porphyrin composite nanoparticle.
2. the preparation method with targeting ferroso-ferric oxide-porphyrin composite nanoparticle according to claim 1, redistilled water and alcohol mixeding liquid washing that the volume ratio that it is characterized in that adopting in step 1 redistilled water and ethanol is 1:1.
3. the preparation method with targeting ferroso-ferric oxide-porphyrin composite nanoparticle according to claim 1, is characterized in that adding in step 2 100mL redistilled water.
4. the preparation method with targeting ferroso-ferric oxide-porphyrin composite nanoparticle according to claim 1, is characterized in that at lucifuge condition lower magnetic force, stirring 24h in step 3.
5. the preparation method with targeting ferroso-ferric oxide-porphyrin composite nanoparticle according to claim 1, is characterized in that in step 4 being sucking filtration under-20 ℃ of conditions in temperature.
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| CN108295258A (en) * | 2018-03-22 | 2018-07-20 | 哈尔滨工业大学 | A kind of preparation method and applications of 10-hydroxycamptothecine/Porphyrin-Based Sensitizer compound formulation |
| CN113384533A (en) * | 2021-06-15 | 2021-09-14 | 西南大学 | Preparation of tirapazamine-loaded silk fibroin ferriporphyrin nano material |
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| CN102961337A (en) * | 2012-12-14 | 2013-03-13 | 哈尔滨工业大学 | Preparation method of target compound nano particle |
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| US8075664B1 (en) * | 2007-06-11 | 2011-12-13 | Sandia Corporation | Synthesis of metallic nanoshells on porphyrin-stabilized emulsions |
| CN103157118A (en) * | 2011-12-09 | 2013-06-19 | 沈阳工业大学 | Composite nano-grade novel material based on cancer early-stage integrated detection, diagnoses, and treatment, and preparation method thereof |
| CN102961337A (en) * | 2012-12-14 | 2013-03-13 | 哈尔滨工业大学 | Preparation method of target compound nano particle |
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| CN104524575A (en) * | 2014-12-10 | 2015-04-22 | 哈尔滨师范大学 | Magnetic chlorophyll fluorescent photosensitizer and preparation method thereof |
| CN104531119A (en) * | 2015-01-09 | 2015-04-22 | 哈尔滨工业大学 | Method for preparing supported metallic catalyst based on Fe3O4 |
| CN107952081A (en) * | 2017-11-15 | 2018-04-24 | 广东药科大学 | PH controlled-release target medicament nano transport agents and its preparation method and application |
| CN108295258A (en) * | 2018-03-22 | 2018-07-20 | 哈尔滨工业大学 | A kind of preparation method and applications of 10-hydroxycamptothecine/Porphyrin-Based Sensitizer compound formulation |
| CN108295258B (en) * | 2018-03-22 | 2020-09-01 | 哈尔滨工业大学 | Preparation method of 10-hydroxycamptothecin/porphyrin photosensitizer composite preparation |
| CN113384533A (en) * | 2021-06-15 | 2021-09-14 | 西南大学 | Preparation of tirapazamine-loaded silk fibroin ferriporphyrin nano material |
| CN113384533B (en) * | 2021-06-15 | 2022-02-22 | 西南大学 | Preparation of tirapazamine-loaded silk fibroin ferriporphyrin nano material |
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