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Preparation method of extra small copper sulphide loaded hollow meso-porous silicon targeted nanometer medicine carrying compound

A nano-drug-loading, mesoporous silicon technology, which is applied in drug combinations, pharmaceutical formulations, and medical preparations with inactive ingredients, etc. problem, to achieve excellent biocompatibility and specific targeting function, good potential practical value, and easy operation.

Active Publication Date: 2018-07-27
DONGHUA UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, chemotherapeutic drugs lack specificity, and while killing cancer cells, damage to normal cells cannot be ignored, thus causing serious toxic and side effects to patients during treatment, seriously affecting the quality of life of patients; in addition, long-term use Chemotherapy drugs often produce severe multi-drug resistance to chemotherapy drugs, which eventually leads to treatment failure

Method used

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  • Preparation method of extra small copper sulphide loaded hollow meso-porous silicon targeted nanometer medicine carrying compound
  • Preparation method of extra small copper sulphide loaded hollow meso-porous silicon targeted nanometer medicine carrying compound
  • Preparation method of extra small copper sulphide loaded hollow meso-porous silicon targeted nanometer medicine carrying compound

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0051] (1) Mix 71.4ml of absolute ethanol, 10ml of ultrapure water and 1.9ml of ammonia water and adjust the pH to 9.0, stir the mixed solvent in a water bath at 30°C for 40min, then add 6ml of TEOS, and continue stirring for 1h to obtain solid silica Microsphere sSiO 2 ; then add pre-mixed C containing 5ml TEOS and 2ml octadecyltrimethylsilane 18 The mixture of TMS was stirred for 2 hours, washed with water, and centrifuged to obtain solid silicon particles sSiO coated with mesoporous silicon. 2 @mSiO 2 .

[0052] (2) the sSiO obtained above 2 @mSiO 2 After being evenly divided into 8 parts, it was dispersed in 0.6M sodium carbonate solution, stirred and etched at 80°C for 30min, cooled, centrifuged, washed once with water and twice with ethanol, then dried in vacuum, and then calcined at 550°C for 6h to obtain Hollow Mesoporous Silica Particles HMSs.

[0053] (3) Disperse 0.3 g of the above-obtained HMSs in 60 ml of anhydrous toluene, add 0.4 ml of MPTMS, reflux at 80 ...

Embodiment 2

[0065] Determination of the photothermal conversion performance of the CuS@HMSs-cRGD drug-loaded system in Example 1:

[0066] (1) Prepare CuS@HMSs-cRGD solutions with different concentrations (0.02-0.2mg / ml) and place them in centrifuge tubes, put pure water in the centrifuge tubes as a blank control, assemble the laser and temperature measuring device, and use a power of 1.0W / cm 2 The 808nm near-infrared light irradiates for 5 minutes, and the temperature change of the solution is monitored by a thermocouple to draw the temperature rise curve of the solution with different concentrations, such as Figure 5 As shown in A.

[0067](2) Prepare a series of CuS@HMSs-cRGD aqueous solutions with a concentration of 0.1mg / ml and place them in centrifuge tubes, assemble the laser and temperature measuring device, and use different powers (0.25-1.5W / cm 2 ) of 808nm near-infrared light irradiation for 5 minutes, monitor the temperature change of the solution by a thermocouple and draw...

Embodiment 3

[0070] The CuS@HMSs(DOX)-cRGD drug-loading system obtained in Example 1 was subjected to a triple stimulus-responsive drug release experiment:

[0071] (1) Prepare PBS buffer solution (0.0025~0.08mg / ml) containing DOX with a pH value of 7.4 and acetate buffer solution (0.0025~0.08mg / ml) containing DOX with a pH value of 5.0. The maximum absorption value was detected in the meter, and the DOX standard curve in two pH environments was fitted.

[0072] (2) Take four parts of 5mg CuS@HMSs(DOX)-cRGD and dissolve them in 10ml of PBS buffer solution and 10ml of acetate buffer solution respectively, and place them in four dialysis bags, and add 10mM GSH to two dialysis bags, and then Place the dialysis bag in 30ml of PBS buffer solution with a pH value of 7.4 and acetate buffer solution with a pH value of 5.0 for shaking, take samples at different time points, add fresh buffer solution, and obtain pH response and GSH response drug release curves, Such as Figure 6 As shown in A.

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Abstract

The invention relates to a preparation method of an extra small copper sulphide loaded hollow meso-porous silicon targeted nanometer medicine carrying compound. The method comprises the following steps of using solid SiO2 as a hard template and TEOS and C18TMS mixed solution as a silicon source; coating a layer of mesoporous SiO2 layer to obtain sSiO2@mSiO2; performing sodium carbonate etching toobtain HMSs; performing sulfhydrylation modification; further performing in-situ growth of CuS; then, modifying targeted polypeptide cRGD to obtain CuS@HMSs-cRGD; performing mixing with DOX to obtainCuS@HMSs(DOX)-cRGD. The method is simple; the operation is easy; the reaction conditions are mild; the industrialized implementation prospects are realized; the final products have higher stability, biocompatibility and higher medicine carrying quantity, realizes long-effect slow release, has the triple effect stimulation medicine release performance, and is suitable for tumor tissue micro environment; too high heat is generated under the low-power laser irradiation; the photothermal therapy can be performed.

Description

technical field [0001] The invention belongs to the technical field of nanocarriers, in particular to a method for preparing ultrasmall copper sulfide-loaded hollow mesoporous silicon-targeted nanometer drug-loaded complexes. Background technique [0002] At present, the methods commonly used in clinical treatment of tumors mainly include surgical treatment, radiotherapy, photothermal therapy, photodynamic therapy, immunotherapy, traditional Chinese medicine treatment and chemotherapy. Among them, chemotherapy plays a dominant role in the comprehensive treatment of tumors, effectively inhibiting the invasion of various cancers to life. However, chemotherapeutic drugs lack specificity, and while killing cancer cells, the damage to normal cells cannot be ignored, so they will cause serious toxic and side effects to patients during treatment, seriously affecting the quality of life of patients; in addition, long-term use Chemotherapy drugs often produce severe multi-drug resis...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K47/69A61K31/704A61K41/00A61K47/62A61P35/00
CPCA61K31/704A61K41/0052A61K47/62A61K47/6949A61P35/00A61K2300/00
Inventor 朱利民吴建荣史梦晗牛世伟李得见
Owner DONGHUA UNIV
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