Prostate cancer targeting gene oligonucleotide aptamer, delivery carrier, delivery system and preparation method thereof

A technology targeting genes and prostate cancer, applied in other methods of inserting foreign genetic materials, gene therapy, pharmaceutical formulations, etc., can solve the problems of difficult monoclonal antibody synthesis, high cost, poor stability, etc., and increase transfection efficiency and expression level, improved expression efficiency, and strong stability

Inactive Publication Date: 2011-12-07
SECOND MILITARY MEDICAL UNIV OF THE PEOPLES LIBERATION ARMY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the main targeting head group currently used is monoclonal antibody. Monoclonal antibody has defects such as difficult synthesis, high cost, and poor stability, which has become a bottleneck restricting its further development to clinical mass production.

Method used

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  • Prostate cancer targeting gene oligonucleotide aptamer, delivery carrier, delivery system and preparation method thereof
  • Prostate cancer targeting gene oligonucleotide aptamer, delivery carrier, delivery system and preparation method thereof
  • Prostate cancer targeting gene oligonucleotide aptamer, delivery carrier, delivery system and preparation method thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0040] In the present invention, by modifying the first-generation aptamer A10, the length of 79 nucleotides of the original aptamer A10 is cut to a novel second-generation aptamer A10-3.2 with a length of 39 nucleotides. The prostate cancer targeting gene described in this example uses the A10-3.2 oligonucleotide aptamer as the targeting head group, and the base composition of the A10-3.2 oligonucleotide aptamer is: 5'-GGGAGGACGAUGCGGAUCAGCCAUGUUUACGUCACUCCU(SEQ .ID.NO.1). The specific composition of the oligonucleotide adapter is: 5′-GGGAGGACGAUGCGGAUCAGCCAUGUUUACGUCACUCCU-(CH 2 ) 6 -S-S-(CH 2 ) 6 -OH-3', and has a 2'-fluoro modification, and has a 2'-fluoro modification.

[0041] The prostate cancer-targeted gene delivery carrier described in this example is based on PAMAM, PEG and the above-mentioned A10-3.2 oligonucleotide aptamer, and the three are covalently linked, wherein, PEG and PAMAM The molar ratio is 2:1, and the molar ratio of the A10-3.2 oligonucleotide ap...

Embodiment 2

[0048] The oligonucleotide aptamer of the prostate cancer targeting gene described in this example is as described in Example 1.

[0049] The prostate cancer targeted gene delivery carrier described in this example is based on PLR, PEG and the above-mentioned A10-3.2 oligonucleotide aptamer, and the three are covalently linked to form, wherein, PEG and PLR The molar ratio is 2:1, and the molar ratio of the A10-3.2 oligonucleotide aptamer to the polycation polymer material is 4:1.

[0050] The preparation method of the prostate cancer-targeted gene delivery carrier described in this embodiment comprises the following steps:

[0051] A. PLR and PEG containing bifunctional groups were dissolved in phosphate buffer solution (PBS) at pH 8.0 according to the molar ratio of 1:2, stirred at room temperature for 2 hours to generate PLR-PEG, and unreacted PEG was removed by ultrafiltration and replaced The buffer is PBS at pH 7.0;

[0052] B. Dissolve the synthesized A10-3.2 oligonucl...

Embodiment 3

[0056] The oligonucleotide aptamer of the prostate cancer targeting gene described in this example is as described in Example 1.

[0057] The prostate cancer targeting gene delivery carrier described in this example is based on PEI, PEG and the above-mentioned A10-3.2 oligonucleotide aptamer, and the three are covalently linked to form, wherein, PEG and PLR The molar ratio is 2:1, and the molar ratio of the A10-3.2 oligonucleotide aptamer to the polycation polymer material is 4:1.

[0058] The preparation method of the prostate cancer-targeted gene delivery carrier described in this embodiment comprises the following steps:

[0059] A. PEI and PEG containing bifunctional groups were dissolved in phosphate buffer solution (PBS) at pH 8.0 according to the molar ratio of 1:2, stirred and reacted at room temperature for 2 hours to generate PEI-PEG, unreacted PEG was removed by ultrafiltration and replaced The buffer is PBS at pH 7.0;

[0060] B. Dissolve the synthesized A10-3.2 ...

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Abstract

The invention discloses an oligonucleotide aptamer for prostate cancer targeting gene, a delivery carrier, a delivery system and a preparation method thereof. The delivery carrier is made of polycationic polymer material, hydrophilic polymer and Based on the oligonucleotide aptamer, the three are covalently linked, wherein the molar ratio of the hydrophilic polymer to the polycation polymer is 1-25:1, and the oligonucleotide aptamer The molar ratio of the body to the polycation polymer material is 1-5:1; the delivery system is a nanoscale gene delivery system formed by delivery carriers and miRNA, siRNA or plasmid DNA. The delivery carrier and the delivery system of the present invention can effectively improve the gene transfection efficiency and expression efficiency on prostate cancer cells expressing prostate specific membrane antigen, compared with the gene delivery system constructed by targeting the head group used in the prior art , which has the advantages of stronger stability and significantly improved targeting effect.

Description

technical field [0001] The invention relates to the field of biotechnology, in particular to an oligonucleotide aptamer, a delivery carrier, a delivery system and a preparation method thereof. Background technique [0002] Prostate cancer (PCa) is the most common malignant tumor of the male reproductive system, and its incidence increases with age. It has become a malignant disease that seriously threatens human health. In the statistical report released by the American Cancer Society in 2010, the incidence of prostate cancer ranked first in men, and the mortality rate ranked second, second only to lung cancer. For the treatment of PCa, early complete surgical resection of the prostate is the preferred treatment, but surgical treatment will be accompanied by serious complications and iatrogenic damage, and it is not effective for metastatic PCa. At present, radiotherapy and chemotherapy (including endocrine therapy) are mainly used in the clinical treatment of advanced PCa....

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C12N15/115C12N15/87C08G81/00A61K47/34A61K48/00A61P35/00
Inventor 高申武鑫朱全刚高静丁雪鹰丁宝月范伟王翔张玮韩雁王晓宇叶丽华张敏
Owner SECOND MILITARY MEDICAL UNIV OF THE PEOPLES LIBERATION ARMY
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