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Tumor-targeted adenovirus polymer drug delivery system and preparation method thereof

A drug delivery system and tumor-targeting technology, which is applied in the field of tumor-targeted adenovirus polymer drug delivery system, can solve the problems of poor tumor targeting, strong immunogenicity of treatment, and less cell uptake, and achieve enhanced expression and accelerated drug delivery. Effect of cellular uptake and widening application range

Inactive Publication Date: 2015-07-08
张雅洁 +1
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  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0016] The purpose of the present invention is to provide a tumor-targeted adenovirus polymer drug delivery system ACPPs-pc-Ad.mda-7, which overcomes the strong immunogenicity, poor tumor targeting and less cell uptake of the existing adenovirus anti-tumor therapy. defect

Method used

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  • Tumor-targeted adenovirus polymer drug delivery system and preparation method thereof
  • Tumor-targeted adenovirus polymer drug delivery system and preparation method thereof
  • Tumor-targeted adenovirus polymer drug delivery system and preparation method thereof

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specific Embodiment approach

[0044] 1. Synthesis of pHPMA (pHPMA-ONp)

[0045] ①Synthesis of HPMA

[0046] 100 ml (1.01 mol) of methacryloyl chloride was added to an acetonitrile solution containing 160 ml (2.02 mol) of 1-amino-2-propanol, and the mixture was stirred at room temperature for 30 min. The precipitate was filtered off. Then, the filtrate was kept at -50°C, and a white precipitate gradually formed, which was placed for 0.5 h until the precipitate was completely precipitated. After filtration, the precipitate was recrystallized from acetone.

[0047] ②Synthesis of N-methacryloylglycylglycine p-nitrophenyl ester (MA-GG-ONp)

[0048] 5.24 g of glycylglycine (0.04 mol) was dissolved in 4N NaOH solution, 0.04 mol of methacryloyl chloride and 10 ml of 4N NaOH solution were added. Stir at room temperature for 2 h, acidify to pH 2, and recrystallize the precipitate with 50% ethanol / water to obtain N-methacryloylglycylglycine. Dissolve 5g (0.025mol) of the above crystallized N-methacryloylglycylgl...

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Abstract

The present invention provides a tumor-targeted adenovirus polymer drug delivery system, which has the following characteristics that (1) a targeted molecule ACPPs and tumor MMPs overexpression generation enzyme are subjected to an enzyme-substrate reaction so as to provide the tumor targeting property; (2) the adenovirus delivery immune clearance effect is reduced, wherein the immune clearance of the reaction product ACPPs-pc-Ad.mda-7. egfp is less, such that the circulating half-life is long so as to reduce the adenovirus delivery amount and increase the adenovirus therapy effect; (3) the adenovirus is positioned in the cytoplasm so as to easily express the therapy gene, wherein the adenovirus is mediated to across the cell membrane barrier through the membrane penetrating mechanism of ACPPs and is positioned in the cell cytoplasm so as to solve the problems of difficult macromolecule drug transmembrane transportion and low therapy gene expression efficiency; and (4) the anti-tumor spectrum is wide. According to the present invention, the drug delivery system is the melanoma differentiation associated gene, such that the growth inhibition and the apoptosis of a variety of cancer cells can be promoted, and significant advantages are provided for anti-tumor, tumor inhibition, toxic-side effect reducing and other fields.

Description

technical field [0001] The invention relates to a drug delivery system, in particular to a tumor-targeted adenovirus polymer drug delivery system. Background technique [0002] Adenoviral vector-mediated gene therapy has been widely used in anti-tumor research. A large number of studies have shown that anti-tumor adenovirus can promote tumor cell growth inhibition and apoptosis, cause a strong bystander anti-tumor effect, and can resist angiogenesis and treat metastatic lesions. It can also be combined with other therapeutic measures to amplify certain immunity. killing effect. The use of anti-tumor adenovirus and other biotechnologies to treat tumors has become a hot spot in the field of tumor research. [0003] However, adenovirus has the following two problems in clinical application: 1. High immunogenicity. The body's natural immune system clears 90% of the viral genome within 24 hours, and the subsequent activation of specific immunity will also clear part of the ade...

Claims

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Application Information

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IPC IPC(8): A61K48/00A61P35/00G01N21/31G01N15/14G01N21/00C08F220/58C08F220/60C12N15/861
Inventor 张雅洁李书华
Owner 张雅洁
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