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Liver targeting cationic polymer as well as preparation method and application thereof

A cationic polymer, ionic polymer technology, applied in the field of biomedicine, to achieve the effects of inhibiting proliferation, high anticancer activity, and enhancing stability

Inactive Publication Date: 2016-11-02
SHANDONG RES INST OF TUMOUR PREVENTION TREATMENT
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Although polycations are superior to viral gene vectors in terms of host immunogenicity, flexibility, and synthesis, their in vivo toxicity, transfection efficiency, and targeting performance still need to be improved

Method used

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  • Liver targeting cationic polymer as well as preparation method and application thereof
  • Liver targeting cationic polymer as well as preparation method and application thereof
  • Liver targeting cationic polymer as well as preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0043] Example 1 Preparation of Liver Targeting Cationic Polymer PuPGEA and Liver Targeting Nanocomposite

[0044] A method for preparing a liver-targeted cationic polymer, the steps are as follows:

[0045] (1) After completely dissolving pullulan (Pullulan, 3g) and 4-dimethylaminopyridine (DMAP, 0.15g) in anhydrous dimethylformamide (DMF, 30mL), in an ice bath and stirring A solution of 2-bromoisobutyryl bromide (BIBB, 0.148 mL) in DMF (0.6 mL) was added under conditions. Then the system was transferred to normal temperature to react for 24 hours, and then bromoisobutyl functionalized pullulan (PuBr) as a polymerization initiator was obtained by dialysis and freeze-drying.

[0046] (2) Put 80 mg of PuBr into anhydrous dimethyl sulfoxide (DMSO, 2 mL), glycidyl methacrylate (GMA, 0.8 mL), cuprous bromide (CuBr) and 2,2'- Bipyridine (Bipy) was added to the above DMSO at a molar ratio of 100:1:3, nitrogen gas was introduced into the mixture by bubbling for 20 minutes, sealed, ...

Embodiment 2

[0058] Example 2 Preparation of liver-targeting cationic polymer PuPGEA and liver-targeting nanocomposite

[0059] A method for preparing a liver-targeted cationic polymer, the steps are as follows:

[0060] (1) After completely dissolving pullulan (Pullulan, 2g) and 4-dimethylaminopyridine (DMAP, 0.438g) in anhydrous dimethylformamide (DMF, 20mL), the A solution of 2-bromoisobutyryl bromide (BIBB, 0.19 mL) in DMF (1.0 mL) was added under conditions. Then the system was transferred to normal temperature to react for 24 hours, and then bromoisobutyl functionalized pullulan (PuBr) as a polymerization initiator was obtained by dialysis and freeze-drying.

[0061] (2) Put 30 mg of PuBr into anhydrous dimethyl sulfoxide (DMSO, 1 mL), glycidyl methacrylate (GMA, 0.5 mL), cuprous bromide (CuBr) and 2,2'- Bipyridine (Bipy) was added to the above-mentioned DMSO at a molar ratio of 80:1:3, and nitrogen gas was passed through by bubbling for 20 minutes, then sealed, and then reacted at...

Embodiment 3

[0066] Example 3 Preparation of Liver Targeting Cationic Polymer PuPGEA and Liver Targeting Nanocomposite

[0067] A method for preparing a liver-targeted cationic polymer, the steps are as follows:

[0068] (1) After completely dissolving Pullulan (Pullulan, 4g) and 4-dimethylaminopyridine (DMAP, 576mg) in anhydrous dimethylformamide (DMF, 40mL), in ice bath and stirring conditions A solution of 2-bromoisobutyryl bromide (BIBB, 0.54 mL) in DMF (5 mL) was added. Then the system was transferred to normal temperature to react for 24 hours, and then bromoisobutyl functionalized pullulan (PuBr) as a polymerization initiator was obtained by dialysis and freeze-drying.

[0069] (2) Put 0.1 g of PuBr into anhydrous dimethyl sulfoxide (DMSO, 3 mL), glycidyl methacrylate (GMA, 0.9 mL), cuprous bromide (CuBr) and 2,2' -Bipyridine (Bipy) was added to the above-mentioned DMSO at a molar ratio of 120:1:3, and nitrogen gas was passed through by bubbling for 20 minutes, then sealed, and th...

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Abstract

The invention relates to a liver targeting cationic polymer as well as a preparation method and an application thereof. The liver targeting cationic polymer is prepared by connecting BUCT-PGEA side chains to a pullulan main chain randomly. The invention also relates to the preparation method and the application of the liver targeting cationic polymer. The invention firstly discloses a nanometer compound which is formed by the PuPGEA with carried MEG3 and P53 genes together, and the nanometer compound has a higher anticancer activity than the nanometer compound which carries pcDNA-MEG3 and pcDNA-P53 individually in HepG2 and SMMC7721 cells; co-transmission of MEG3 and P53 has additional effects for external growth of HCC cells.

Description

technical field [0001] The invention relates to a liver-targeting cationic polymer and its preparation method and application, in particular to a preparation method and application of a liver-targeting cationic polymer (gene carrier) and a liver-targeting nanocomposite, belonging to the technical field of biomedicine . Background technique [0002] Hepatocellular carcinoma (HCC) is a primary liver cancer with a high mortality rate. It ranks second among the 10 most common malignant tumors worldwide. A large number of pathogenic factors have been proven to cause this malignancy, such as: infection with hepatitis B virus (HBV) or hepatitis C virus (HCV); consumption of food contaminated with aflatoxin B and alcohol abuse. However, only some of the individuals affected by the above-mentioned pathogenic factors will develop HCC, suggesting that there are also genetic factors involved in the formation of HCC. Among these genetic factors, long non-coding RNAs (lncRNAs) play a v...

Claims

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Application Information

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IPC IPC(8): C08F251/00C08F220/32C08F8/32C08B37/00A61K31/7088A61K47/36A61P35/00A61P1/16
CPCA61K31/7088A61K47/36C08B37/00C08F8/32C08F251/00C08F220/325
Inventor 杨明徐福建李瑞全任艳利
Owner SHANDONG RES INST OF TUMOUR PREVENTION TREATMENT
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