Brain tumour targeting gene delivery composite modified by low density lipoprotein receptor associated protein ligand polypeptide

A receptor-related protein, low-density lipoprotein technology, used in anti-tumor drugs, gene therapy, inactive components of polymer compounds, etc. The effect of diffusion, brain targeting efficiency improvement

Inactive Publication Date: 2012-08-01
FUDAN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] The purpose of the present invention is to provide a new brain tumor-targeted gene delivery complex for the problems of low brain entr

Method used

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  • Brain tumour targeting gene delivery composite modified by low density lipoprotein receptor associated protein ligand polypeptide
  • Brain tumour targeting gene delivery composite modified by low density lipoprotein receptor associated protein ligand polypeptide
  • Brain tumour targeting gene delivery composite modified by low density lipoprotein receptor associated protein ligand polypeptide

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0085] PAMAM and PEG containing bifunctional groups were dissolved in PBS at pH 8.0 according to the molecular ratio of 1:2, stirred at room temperature for 2 hours to generate PAMAM-PEG, unreacted PEG was removed by ultrafiltration and the buffer was replaced with PBS at pH 7.0 . Angiopep and PAMAM-PEG were mixed according to a molecular ratio of 1:1, stirred and reacted at room temperature for 24 hours to generate PAMAM-PEG-Angiopep.

Embodiment 2

[0087] PAMAM and PEG containing bifunctional groups were dissolved in PBS at pH 8.0 according to the molecular ratio of 1:5, stirred at room temperature for 2 hours to generate PAMAM-PEG, unreacted PEG was removed by ultrafiltration and the buffer was replaced with PBS at pH 7.0 . Angiopep and PAMAM-PEG were mixed according to a molecular ratio of 1:1, stirred and reacted at room temperature for 24 hours to generate PAMAM-PEG-Angiopep.

Embodiment 3

[0089] 1.0 mg of the PAMAM-PEG-Angiopep polymer carrier prepared in Example 1 was dissolved in 0.5 ml of heavy water, and the structure of the polymer carrier was identified by a Mercury Plus 400 MHz superconducting nuclear magnetic resonance spectrometer. At the same time, 1.0 mg of bifunctional group PEG was dissolved in 0.5 ml of heavy water, and the structure was identified by Mercury Plus 400 MHz superconducting NMR spectrometer. The spectra of the two were analyzed, and it was concluded that PAMAM-PEG-Angiopep was successfully synthesized (as shown in Figure 1).

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Abstract

The invention, belonging to the field of biotechnology, relates to a brain tumor targeting gene delivery composite modified by low density lipoprotein receptor associated protein ligand polypeptide. The brain tumor targeting gene delivery composite has a dual targeting effect of BBB and glioma. Therapeutic genes can express and kill tumor cells in glioma cells, and can release gene product TRAIL protein into the environment outside the cells to combine with tumor cells by the means of cell paracrine after expressing in BCECs and then have a killing effect, thus aiming at the infiltrative growth characteristic of glioma in the brain, the brain tumor targeting gene delivery composite can kill the main glioma and simultaneously effectively inhibit the diffusion of scattered tumor cells.

Description

technical field [0001] The invention belongs to the field of biological technology, and relates to a brain tumor targeting gene delivery complex, in particular to a brain tumor targeting gene delivery complex modified by a low-density lipoprotein receptor-related protein ligand polypeptide. Background technique [0002] Studies have shown that the blood-brain barrier (BBB) ​​can effectively prevent exogenous harmful substances from entering the brain, thereby ensuring the stability of the brain environment and brain function. The BBB is mainly composed of brain capillary endothelial cells (BCECs for short), and the tight junctions between cells prevent most drugs, such as antibiotics, antineoplastic drugs, neuropeptides, and other active drugs, from entering the central nervous complex. Studies have shown that almost all large-molecule drugs such as gene drugs and more than 98% of small-molecule drugs cannot pass through the BBB. [0003] Current strategies to increase drug...

Claims

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Application Information

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IPC IPC(8): A61K48/00A61K47/42A61K47/34A61P35/00
Inventor 蒋晨邵堃柯伟伦黄容琴
Owner FUDAN UNIV
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