Looking for breakthrough ideas for innovation challenges? Try Patsnap Eureka!

Oligonucleotide/atom fine nanocluster compound capable of efficiently penetrating through blood brain barrier and preparation method and application thereof

A technology of oligonucleotide and nanocluster, which is applied in the field of oligonucleotide/atom fine nanocluster complex and its preparation, can solve the problems of lack of efficient materials for crossing the blood-brain barrier, and achieve good biological learning effect, improving crossing efficiency, and efficient crossing effect

Pending Publication Date: 2020-11-27
SHANGHAI ADVANCED RES INST CHINESE ACADEMY OF SCI
View PDF9 Cites 2 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004] The purpose of the present invention is to provide an oligonucleotide / atomic fine nano-cluster complex that efficiently crosses the blood-brain barrier and its preparation method and application, thereby solving the problem of lack of efficient blood-brain barrier materials in the prior art question

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
  • Oligonucleotide/atom fine nanocluster compound capable of efficiently penetrating through blood brain barrier and preparation method and application thereof
  • Oligonucleotide/atom fine nanocluster compound capable of efficiently penetrating through blood brain barrier and preparation method and application thereof
  • Oligonucleotide/atom fine nanocluster compound capable of efficiently penetrating through blood brain barrier and preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0044] The atomically fine gold nanoclusters protected by oligonucleotides in this example include Au8 clusters with a specific structure, containing 40 thymines (T 40 ) single-stranded oligonucleotide, and dimethylformamide, an organic solvent miscible with water.

[0045] The preparation method of the atomically fine gold nanoclusters protected by the oligonucleotide is as follows:

[0046] 1) Dissolve Au8 in acetonitrile to a final concentration of 100 μM;

[0047] 2) Put T 40 Single-stranded oligonucleotides were dissolved in deionized water to a final concentration of 100 μM;

[0048] 3) Take 200 μL of the Au8 solution and add 100 μL of T 40 Add 100 μL of water-miscible dimethylformamide to the single-stranded oligonucleotide solution, mix well, shake at 400 rpm at room temperature for 12 hours overnight at 25°C.

[0049] 4) Add 3mL of deionized water to the mixed solution obtained in step 3), use a K ultrafiltration tube, 12000rpm, ultrafiltration three times for 15m...

Embodiment 2

[0053] Oligonucleotide-protected atomically fine gold nanoclusters cross the blood-brain barrier in mice as follows:

[0054] 1) The aqueous solution of atomically fine gold nanoclusters protected by oligonucleotides obtained in Example 1 was mixed with 10xPBS at a ratio of 9:1, and sonicated for 30 minutes.

[0055] 2) Use a 1mL syringe to inject into the mouse body through the tail vein, and observe the fluorescence of the mouse brain (1h, 6h, 12h, 36h) with a small animal in vivo imager. The results are as follows Figure 4 shown.

[0056] 3) After 12 hours of administration, the mice were dissected, and the mouse brain tissue was taken for frozen section observation. The thickness of the slice was 10 μm. DAPI was used to stain the nucleus of the mouse brain tissue, and the red color of the brain could be seen under fluorescent confocal microscope observation. Fluorescence is the atomically fine gold nanoclusters protected by oligonucleotides in the present invention, such...

Embodiment 3

[0059] 1) Culture human blood-brain barrier brain endothelial cells bEnd.3 to 1×10 5 About (100×20mm Petri dish, Corning, USA). The culture conditions are: containing growth factors, DMEM medium (Gibco LifeTechnologies Inc., UK), adding 10% (v / v) fetal bovine serum, penicillin and streptomycin (100U / mL, Sigma-Aldrich) and streptomycin (100 μg / mL, Sigma-Aldrich), 37 ° C, 5% CO 2 cultivated under conditions.

[0060] 2) Mix the atomically fine gold nanoclusters protected by the oligonucleotide obtained in Example 1 with the medium, and the final concentration of the gold clusters is 2 μM. After incubation with the cells at 37°C for 30 min, observed under a confocal fluorescence microscope, it can be seen that atomically fine gold nanoclusters protected by oligonucleotides can be effectively taken up by brain endothelial cells. Such as Figure 7 shown.

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 provides an oligonucleotide / atom fine nanocluster compound capable of efficiently penetrating through a blood brain barrier. The oligonucleotide / atom fine nanocluster compound is composed of oligonucleotide and hydrophobic atom fine nanocluster, and is viroid particles which has a hydrophilic oligonucleotide shell and has a hydrophobic atom fine nanocluster core, wherein the oligonucleotide is an oligonucleotide single chain formed by arranging at least one of adenine, guanine, cytosine and thymine according to any combination, and the hydrophobic atom fine nanocluster is a cluster of hydrophobic metal atoms with an atom fine structure. The oligonucleotide / atom fine nanocluster compound provided by the invention provides an effective drug carrier for brain near-infrared imaging and imaging and treatment of brain tumors or neurodegenerative diseases.

Description

technical field [0001] The invention belongs to the field of nano-biological materials, and in particular relates to an oligonucleotide / atom fine nano-cluster complex efficiently passing through the blood-brain barrier, a preparation method and application thereof. Background technique [0002] The Blood-Brain Barrier (BBB) ​​is an international problem in the treatment of brain diseases. Because of its existence, 100% of macromolecular drugs and more than 98% of small molecule drugs cannot pass through and reach brain tissue, which greatly limits the efficacy of drugs on brain diseases. Therefore, the invention of a biomaterial or drug carrier that can effectively penetrate the blood-brain barrier has been highly anticipated. [0003] The blood-brain barrier is a special structure mainly composed of brain capillary endothelial cells, sticky ends of astrocytes and tight junctions of pericytes. Under normal physiological conditions, the blood-brain barrier only allows gases...

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
Patent Type & Authority Applications(China)
IPC IPC(8): A61K47/02A61K47/26A61K49/00A61K48/00
CPCA61K47/02A61K47/26A61K49/0019A61K49/0052A61K48/00
Inventor 王丽华樊春海沈建磊谷沛霖李宇陈静诸颖
Owner SHANGHAI ADVANCED RES INST CHINESE ACADEMY OF SCI
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Patsnap Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Patsnap Eureka Blog
Learn More
PatSnap group products

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

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap|About US| Contact US: help@patsnap.com