Preparation method of targeted ferroferric oxide-porphyrin containing composite nanoparticles

A technology of composite nanoparticles and ferric oxide, which is applied in medical preparations with non-active ingredients, medical preparations containing active ingredients, organic active ingredients, etc., can solve the problem of weak fluorescence signal intensity of photosensitizers and tumor tissue selection. The problem of low sexual uptake and high cumulative effect of photosensitizers can achieve the effect of inhibiting tumor metastasis, improving immunity and reducing diffusion

Inactive Publication Date: 2014-02-05

HARBIN INST OF TECH

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Problems solved by technology

[0003] The present invention aims to solve the problems of photodynamic diagnosis and treatment that the fluorescent signal intensity of the photosensitizer is not strong, and the selective uptake of tumor tissue is not high, resulting in a high ...

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.

Application Domain

Powder deliveryOrganic active ingredients +3

Technology Topic

Folic acidOxide +12

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Experimental program(6)

Example Embodiment

[0026] Specific embodiment 1: This embodiment has a method for preparing targeted ferroferric oxide-porphyrin composite nanoparticles, which is specifically carried out according to the following steps:

[0027] 1. Using FeCl 3 ·6H 2 O prepares FeCl with a concentration of 0.1 mol/L 3 Solution using FeSO 4 ·4H 2 O prepares FeSO with a concentration of 0.1 mol/L 4 Solution

[0028] Under nitrogen protection and mechanical stirring conditions, according to Fe 3+ With Fe 2+ The molar ratio is 2:1, and 100mL FeCl with a concentration of 0.1mol/L 3 Solution and 50mL FeSO with a concentration of 0.1mol/L 4 Mix the solution to get FeCl 3 And FeSO 4 Then, use hydrochloric acid with a concentration of 1mol/L to adjust the pH to 5, and then add an aqueous ammonia solution with a mass concentration of 25% until the mixed solution appears black precipitation, and then continue to stir for 1h to obtain a solid-liquid mixture;

[0029] Under the action of an external magnetic field, the upper waste liquid of the solid-liquid mixture is poured, and then the precipitate is washed with deionized water to obtain Fe 3 O 4 Magnetic nanoparticles; Fe 3 O 4 Magnetic nanoparticles are dispersed in NaCl aqueous solution with a concentration of 0.4mol/L to Fe 3 O 4 The concentration of the magnetic nanoparticles is 7.5mg/mL to obtain mixed solution A, then take 10mL of mixed solution A and add 30mL of ethanol solution with 1.5mL of tetraethoxysilane, and then add 30mL of deionized water, 30mL of absolute ethanol and 2.5 mL ammonia water with a mass concentration of 28%, continue stirring for 90 minutes, then remove the supernatant by magnetic separation, and then wash the magnetic nanoparticles with a mixture of twice distilled water and ethanol 3 times to obtain a silica-coated magnetic ferroferric oxide Nanoparticles;

[0030] 2. Mix 150mg of tetrahydroxyphenylporphyrin compound, 2g of anhydrous potassium carbonate and 40mL of N,N-dimethylformamide, stir with a magnetic stirrer filled with ice brine for 10 minutes, and then add 1.5mL of chloroacetyl chloride , Continue the reaction for 4.5h under the condition of ice-salt bath, add 90mL~110mL double distilled water, then extract with 100mL dichloromethane, and remove the lower layer solution;

[0031] The resulting lower layer solution was dried with anhydrous sodium sulfate for 24 hours, and the solvent was evaporated to dryness with a rotary evaporator to obtain a mixture of different porphyrin compounds substituted by chloroacetyl chloride, which was then separated by silica gel column chromatography, using pure dichloromethane as the eluent , The compound of the first chromatographic band is obtained, and the mixed solution of dichloromethane and methanol with a volume ratio of dichloromethane and methanol of 100:1 is used as the eluent to obtain the compound of the second chromatographic band. The mixed eluent of dichloromethane and methanol with a volume ratio of 100:1.5 is used as the eluent to obtain the compound of the third chromatographic band, and then a mixture of dichloromethane and methanol with a volume ratio of dichloromethane and methanol of 100:1.8 The lotion is used as the eluent to obtain the compound in the fourth chromatographic band, and the mixed eluent of dichloromethane and methanol with a volume ratio of dichloromethane to methanol of 100:2.5 is used as the eluent to obtain the fifth chromatographic band Compound 1, wherein the structural formula of Compound 1 is

[0032] 3. Mix 100mg of compound 1, 2g of anhydrous potassium carbonate obtained in step 2, 1.5mL of chloropropyltriethoxysilane and 20mL of tetrahydrofuran, stir magnetically for 20h-28h under dark conditions, filter again, and distill under reduced pressure Remove the unreacted silane reagent and tetrahydrofuran to obtain crude siloxane porphyrin; then use silica gel as a stationary phase and a mixed solution of dichloromethane and methanol with a volume ratio of dichloromethane and methanol of 1:5 as eluent for leaching Wash, collect the compounds in the first chromatographic band to obtain a porphyrin compound bonded with a silane reagent. The structural formula of the porphyrin compound is

[0033] 4. Combine 50 mg of the porphyrin compound obtained in step 3 and 4 g of anhydrous K at room temperature 2 CO 3 Dissolve in 30mL DMSO, then add 40mg of folic acid, stir magnetically for 10h at room temperature and avoid light, then add 300mL of frozen ether, and then suction filter at a temperature of -15℃~-22℃ to obtain a purple solid, and then use Washing with glacial ether at a temperature of -20°C to obtain a folate-linked porphyrin-folate compound, the structural formula of the porphyrin-folate compound is

[0034] 5. Disperse the silica-coated magnetic ferroferric oxide nanoparticles obtained in step 1 into a mixed solvent of 30 mL alcohol and 30 mL deionized water by ultrasound, control the temperature to 60°C, and add 20 mg under mechanical stirring. The obtained porphyrin-folate compound is then reacted at 60° C. for 2 hours and then subjected to magnetic separation to obtain targeted ferroferric oxide-porphyrin composite nanoparticles.

Example Embodiment

[0035] Specific embodiment two: This embodiment is different from specific embodiment one in that step one uses a mixture of twice distilled water and ethanol with a volume ratio of twice distilled water and ethanol of 1:1 for washing. Others are the same as the first embodiment.

Example Embodiment

[0036] Specific embodiment three: This embodiment is different from specific embodiment one in that 100 mL of double distilled water is added in step two. Others are the same as the first embodiment.

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Nanocomposite with low skin phototoxicity for sonodynamic therapy as well as preparation method and application of nanocomposite

PendingCN114796487AReduce phototoxicityreduce defense

Owner:TIANJIN UNIVERSITY OF SCIENCE AND TECHNOLOGY

Classification and recommendation of technical efficacy words

Reduce phototoxicity
reduce dispersion

Nanocomposite with low skin phototoxicity for sonodynamic therapy as well as preparation method and application of nanocomposite

PendingCN114796487AReduce phototoxicityreduce defense

Owner:TIANJIN UNIVERSITY OF SCIENCE AND TECHNOLOGY

Preparation method of targeted ferroferric oxide-porphyrin containing composite nanoparticles

AI-Extracted Technical Summary

Problems solved by technology

Abstract

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Examples

Example Embodiment

Example Embodiment

Example Embodiment

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Description & Claims & Application Information

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