Functional dendritic polymer gene vector system of targeted malignant cerebroma

A technology of dendrimers and gene carriers, which is applied in the field of biomedicine, can solve the problems of lower transfection efficiency than adenovirus and limited use, and achieve good therapeutic effect, efficient transfection, and the effect of inhibiting tumor growth

Inactive Publication Date: 2009-01-07
GENERAL HOSPITAL OF TIANJIN MEDICAL UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

However, the transfection efficiency of these reagents is usually not as good as that of adenovirus-like recombinant vectors, thus significantly limiting their use

Method used

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  • Functional dendritic polymer gene vector system of targeted malignant cerebroma
  • Functional dendritic polymer gene vector system of targeted malignant cerebroma
  • Functional dendritic polymer gene vector system of targeted malignant cerebroma

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0034] (1) Dissolve 1 mg of folic acid in 1 mL of dimethyl sulfoxide to obtain solution A. (2) 10 mg of polyamide-amine 5th generation dendrimer was dissolved in 1 mL of deionized water to obtain solution B. (3) 3 mg of EDC was dissolved in 1 mL of sodium carbonate-sodium bicarbonate buffer solution to obtain solution C. Mix solution A and solution B uniformly at room temperature, gradually add solution C dropwise, and react for 4 hours. The above reaction product is dialyzed against water and then freeze-dried to obtain folic acid-modified polyamide-amine gene carrier. Its transmission electron microscope pictures are as figure 1 a. (4) The folic acid-modified polyamidoamine and 1.25 mg oligonucleotide were vortexed for 10 minutes to obtain a solution D containing a functionalized dendrimer gene carrier system targeting malignant brain tumors. (5) Pass the solution D through a 0.22 membrane, and inject it into the C6 tumor-bearing mice through the tail vein. After 24 hour...

Embodiment 2

[0036] The polyamide used-amine is 3 generation dendrimers, other is with embodiment 1

Embodiment 3

[0038] The polyamido-amine used is 7 generations of dendrimers, and others are the same as in Example 1

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Abstract

The invention relates to a functionalized arborescent macro radical carrier system for targeting malignant cerebroma. The functionalized arborescent macro radical carrier system is obtained by taking one or more of the following combinations as the targeting functional factor: transferrin and transferrin monoclonal antibody, or polyclonal antibody, folic acid (FA) and epidermal growth factor receptor monoclonal antibody, or polyclonal antibody and RGD cyclic peptide, chemically connecting the combinations to arborescent macro radical polyamide-amine (PAMAM) carrier system, and then compounding the combinations with treatment factor oligonucleotide, siRNA molecule or plasmid DNA. Through intra-tumor stereotactic injection, carotid injection or tail vein, the distribution of genes in the malignant cerebroma can be improved, high expression can be realized, and the effective cerebroma inhibition can be realized. Compared with the commercialized gene carrier Oligofectamin and unmodified PAMAM, the FA-PAMAM can remarkably improve the targeting delivery ability of the in vitro and in vivo genes.

Description

【Technical field】: [0001] The invention belongs to the technical field of biomedicine, and in particular relates to a functional dendrimer gene carrier system for targeted malignant brain tumor gene delivery and treatment of malignant brain tumors. 【Background technique】: [0002] Malignant brain tumors are extremely harmful intracranial tumors. From the principles and perspectives of molecular biology and cell biology, it is a type of disease characterized by malignant proliferation of cells. It often shows infiltrative growth without obvious boundaries. Surgery Difficult to remove completely. Compared with tumors in various systems of the body, the average period from the onset of symptoms to death of patients with malignant brain tumors is less than half a year, and the average survival period of surgery plus radiotherapy is less than one year. With comprehensive treatment of surgery, radiotherapy and chemotherapy, the survival rate of malignant glial brain is 45% in 1 y...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K47/48A61K47/34A61K48/00A61P35/00A61K47/59
Inventor 康春生浦佩玉原续波李菲钟跃
Owner GENERAL HOSPITAL OF TIANJIN MEDICAL UNIV
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