Nucleic acid aptamer derivative and application thereof in preparation of medicament carrier

A technology of nucleic acid aptamers and derivatives, applied in biochemical equipment and methods, microbial measurement/testing, drug combination, etc., can solve problems such as difficult chemical modification and transformation, easy to cause immune response, and limit wide application, etc., to achieve Reduced toxicity, no immune activity and toxicity, high application value effect

Active Publication Date: 2011-01-12
谭蔚泓
View PDF0 Cites 26 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the antibodies used for targeted delivery of drugs are derived from animals or fused monoclonal cells, which need to be produced through biological processes. The preparation is cumbersome, high cost, poor stabilit

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Nucleic acid aptamer derivative and application thereof in preparation of medicament carrier
  • Nucleic acid aptamer derivative and application thereof in preparation of medicament carrier
  • Nucleic acid aptamer derivative and application thereof in preparation of medicament carrier

Examples

Experimental program
Comparison scheme
Effect test

Example Embodiment

[0041] Example 1. Characterization of the affinity between nucleic acid aptamer derivatives and human hepatoma cells

[0042] 1. Preparation of nucleic acid aptamers and their derivatives

[0043] Three nucleic acid aptamer derivatives were synthesized artificially, and 1 GC, 29 GC and 50 GC were introduced into the 5' end of the nucleic acid aptamer TLS11a, respectively. TLS11a-(GC) 1 As shown in Sequence 3 of the Sequence Listing. TLS11a-(GC) 29 As shown in Sequence 4 of the Sequence Listing. TLS11a-(GC) 50 As shown in Sequence 5 of the Sequence Listing.

[0044] Three kinds of control nucleic acid aptamer derivatives were artificially synthesized, and 1 GC, 29 GCs and 50 GCs were introduced into the 5' end of the nucleic acid aptamer TD05, respectively. TD05-(GC) 1 As shown in Sequence 6 of the Sequence Listing. TD05-(GC) 29 As shown in Sequence 7 of the Sequence Listing. TD05-(GC) 50 As shown in Sequence 8 of the Sequence Listing.

[0045] The nucleic acid apta...

Example Embodiment

[0053] Example 2. Preparation of nucleic acid aptamer derivative-drug complex

[0054] 1. Nucleic acid aptamer TLS11a and nucleic acid aptamer derivative TLS11a-(GC) 29 preparation

[0055] In order to insert more doxorubicin, a long GC sequence (composed of 29 GCs connected in sequence) was introduced at the 5' end of the nucleic acid aptamer TLS11a, thereby obtaining a nucleic acid aptamer derivative with an extended sequence TLS11a-(GC ) 29 . TLS11a-(GC) 29 As shown in Sequence 4 of the Sequence Listing.

[0056] The nucleic acid aptamer TLS11a shown in SEQ ID NO: 1 of the Sequence Listing was synthesized. The nucleic acid aptamer derivative TLS11a-(GC) shown in SEQ ID NO: 4 of the synthetic sequence listing 29 .

[0057] 2. Preparation and characterization of nucleic acid aptamer derivative-drug complexes

[0058] 1. Preparation of nucleic acid aptamer derivatives-drug complexes

[0059] In binding buffer, the nucleic acid aptamer derivative TLS11a-(GC) 29 It is ...

Example Embodiment

[0077] Example 3. Effects of nucleic acid aptamer derivatives-drug complexes on liver cancer cells

[0078] Determination of chemosensitivity of liver cancer cells LH86 to doxorubicin or aptamer derivative-drug complexes using CellTiter AQueous Single Solution Cell Proliferation Assay Kit (Promega, Madison, WI, USA) was performed. CellTiter AQueous single solution reagents: 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt; MTS and an electron coupling reagent ( thiophenazine, PES). The details are as follows: 100 μL liver cancer cells LH86 (about 5×10 4 cells / mL) were seeded in 96-well plates (n=3) and grown overnight at 37°C (5% CO 2 , FBS-free DMEM medium), then 100 μL of the following DNA strands were added:

[0079] (1) TLS11a; set up four concentration gradients, respectively with TLS11a-(GC) in the nucleic acid aptamer derivative-drug complex in (4) 29 The concentrations were the same, namely 40, 100, 200, 300 n...

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to view more

PUM

No PUM Login to view more

Abstract

The invention discloses a nucleic acid aptamer derivative and application thereof in preparation of a medicament carrier. The derivative is the single-chain DNA represented by formula (I); a nucleic acid aptamer is represented by the sequence 1 of a sequence list; and n is equal to 1 to 50. The nucleic acid aptamer derivative provided by the invention is liver cancer cell targeted, so that the nucleic acid aptamer derivative can serve as the medicament carrier for targeted administration of liver cancer cells in a human body to specifically kill the liver cancer cells and greatly reduce the toxicity of an anti-cancer medicament to the organism. The nucleic acid aptamer derivative provided by the invention can be chemically synthesized in a large scale and has the advantages of easy connection with medicament molecules, low cost, relatively low molecular weight, no immune activity or toxicity, and good stability. The prepared medicinal composition is stable. The medicinal composition (targeted medicament) provided by the invention has a strong bonding force with the liver cancer cells, can greatly reduce the toxic and side effects during chemical treatment of liver cancer and has very high application value. The formula (I) is: 5'-(CG)n-nucleic acid aptamer-3'.

Description

technical field [0001] The invention relates to nucleic acid aptamer derivatives and their application in the preparation of drug carriers. Background technique [0002] Liver cancer is one of the most prevalent and highly lethal cancers in the world. At present, the effective treatment methods for patients with early liver cancer are mainly surgical resection and liver transplantation. Traditional chemotherapy is not effective for patients with liver cancer, and traditional drugs usually bring fatal side effects to patients due to lack of specificity to liver cancer cells. In order to overcome these problems and improve the selectivity of chemotherapy, it is necessary to develop targeted drugs that are administered specifically in tumor regions. [0003] Tumor cell-targeted drug delivery is an effective way to improve the efficacy of tumor therapy and reduce side effects. Conjugating drugs to tumor cell-specific ligands is the main method of targeted drug delivery. For ...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to view more

Application Information

Patent Timeline
no application Login to view more
IPC IPC(8): C12N15/115C12Q1/68C12Q1/02A61K47/48A61P35/00A61K31/704A61K47/54
Inventor 谭蔚泓方晓红刘晨
Owner 谭蔚泓
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Try Eureka
PatSnap group products

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic.

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap