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Tumor-targeted magnetic hydrogel nanoscale medicine delivery system and construction method and application thereof

A hydrogel nano, tumor-targeting technology, applied in the field of anti-cancer drug preparation, can solve the problems of low effective rate of doxorubicin

Inactive Publication Date: 2013-01-16
SOUTH CHINA NORMAL UNIVERSITY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Due to the emergence of drug resistance, the effective rate of doxorubicin is less than 20%. At the same time, due to its obvious toxicity to the blood system and gastrointestinal reactions, it can cause nausea, vomiting, hair loss, high fever and other adverse reactions

Method used

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  • Tumor-targeted magnetic hydrogel nanoscale medicine delivery system and construction method and application thereof
  • Tumor-targeted magnetic hydrogel nanoscale medicine delivery system and construction method and application thereof
  • Tumor-targeted magnetic hydrogel nanoscale medicine delivery system and construction method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0047] Example 1 Preparation and Characterization of Tumor Targeting Magnetic Nano Drug Delivery System

[0048] 1.1 Superparamagnetic Fe 3 O 4 Synthesis and Surface Modification of Nanoparticles

[0049] Ferric oxide (Fe3O4) was synthesized by chemical co-precipitation 3 o 4 )Nanoparticles. Weigh 0.1mol FeSO 4 ·7H 2 O, 0.16mol FeCl 3 ·6H2 O was placed in a three-necked flask, 140ml of ultrapure water was added to it, the three-necked flask was equipped with an electric stirrer, placed in an oil bath, protected by nitrogen, stirred at 60°C for 30min; weighed 0.84mol NaOH and placed Add 280ml of ultrapure water to the beaker, and stir with a glass rod at 60°C to fully dissolve it. Slowly add the NaOH solution into the iron salt solution (pH=12 of the mixed solution at this time), after reacting for 10 minutes, raise the temperature to 70°C, then add the HCl solution to it until the pH=3, and finally add 20ml of oleic acid (Oleic acid , OA), stirred for 3 hou...

Embodiment 2

[0078] Example 2 Fe 3 O 4 -OA / NIPA-AA / TNF-α / IFN- gamma Inhibition of / FA / DOX on HepG2 cells in vitro

[0079] 1 Research on the inhibitory effect of drugs on cells

[0080] Digest HepG2 cells with trypsin and collect, pipette evenly and press 1×10 per well 6 Cells were seeded in 24-well plates. The experiment was divided into four groups: A blank control group (pure cell culture); B free TNF-α (1.5ng / well) + IFN-γ (1.5ng / well) + FA (1.5ng / well) + DOX (20 ng / well); C free Fe 3 o 4 -OA / NIPA-AA(1.5ng / well)+TNF-α(1.5ng / well)+IFN-γ(1.5ng / well)+FA(1.5ng / well)+DOX(20ng / well); D total fixed drug group Fe 3 o 4 -OA / NIPA-AA / TNF-α / IFN-γ / FA / DOX (dosage is calculated as 20ng / well of doxorubicin). Under the same conditions (37℃, 5%CO 2 ) after culturing for 24 hours, compare the cell number of the experimental group with that of the blank group by cell counting, and calculate the cell survival rate.

[0081] Study on the Inhibitory Effect of Different Doses of Nan...

Embodiment 3

[0083] Example 3 Fe 3 O 4 Inhibition of -OA / NIPA-AA / TNF-α / IFN-γ / FA on HepG2 cells in vivo

[0084] 1 Culture of liver cancer cells (HepG2 cell line)

[0085] Use DMEM medium (containing 10% newborn calf serum, 0.03mg / ml penicillin, 0.05mg / ml streptomycin, pH=7.2~7.4), at 37°C, 5%CO 2 subculture in an incubator.

[0086] Establishment of Liver Cancer Animal Model

[0087] Animal experiments selected four-week-old BALB / c-nu / nu nude mice (nude mice), purchased a total of 20, all males, with a body weight of 14.5±3.2g, all purchased from the Production Department of Guangdong Medical Experimental Animal Center, SPF grade, License number: SCXK (Guangdong) 2008-0002; batch of nude mice is 0079266. The nude mice were purchased and fostered in the SPF-level nude mouse room of the Animal Experiment Center on the North Campus of Sun Yat-sen University (permit number SYXK (Guangdong) 2007-0081). 20 nude mice were randomly divided into 5 groups, 4 in each group, numbere...

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Abstract

The invention discloses a tumor-targeting magnetic hydrogel nano drug delivery system as well as its construction method and application. The tumor-targeted magnetic nano-drug delivery system of the present invention grafts temperature- and pH-sensitive hydrogels onto the surface of iron ferric oxide nanoparticles by photochemical immobilization to form a magnetic hydrogel carrier, and grafts branch tumor necrosis factor-α, interferon-γ and targeting molecule ligand folic acid, and then adsorb doxorubicin. The system of the present invention can use active targeting to transport anti-tumor drugs to the surrounding tumor cells. Tumor necrosis factor-α and interferon-γ bind to receptors on the surface of tumor cells and induce programmed death of tumor cells. Anti-tumor drug doxorubicin The hormone is released after entering the cell with the carrier. Experiments have proved that the drug delivery system of the present invention has negligible toxic and side effects, and can efficiently inhibit the growth of cancer cells through the joint action mechanism of tumor necrosis factor-α and interferon-γ in cooperation with anti-tumor drug doxorubicin inside and outside tumor cells.

Description

technical field [0001] The invention relates to the technical field of preparation of anticancer drugs, in particular to a tumor-targeting magnetic hydrogel nano drug delivery system and its construction method and application. Background technique [0002] According to a research report released by the International Cancer Research Center of the World Health Organization in April 2011, according to the current trend of cancer incidence, the incidence of cancer worldwide will increase by 50% in 2020, and the number of new cancer patients worldwide will reach 15 million people. Among these many types of cancers, liver cancer is one of the most common malignant tumors, which has the characteristics of high incidence, short course of disease, high degree of malignancy, and poor prognosis. Western medicine surgery, radiotherapy and chemotherapy, combined with traditional Chinese medicine are generally used clinically, but there are problems such as large toxic and side effect...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K9/00A61K47/32A61K47/02A61K47/22A61K47/48A61K38/21A61K38/19A61K31/704A61P35/00
Inventor 刘俊明关燕清黄峥
Owner SOUTH CHINA NORMAL UNIVERSITY
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