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Nucleic acid nano structure for carrying antitumor drugs, preparation method and applications thereof

An anti-tumor drug and nucleic acid nanotechnology, which is applied in the field of nucleic acid nanostructures carrying anti-tumor drugs and its preparation, can solve the lack of understanding of the enrichment of anti-tumor drugs to reduce the systemic toxicity, specificity and systemic toxicity of anti-tumor drugs, etc. question

Inactive Publication Date: 2015-02-25
THE NAT CENT FOR NANOSCI & TECH NCNST OF CHINA +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] Although, through analysis, it can be seen that nucleic acid nanostructures have the above advantages, but there is no report on the use of nucleic acid nanostructures as carriers of antitumor drugs for human or animal tumor treatment.
The main reason is that there is still a lack of understanding of the specificity and systemic toxicity of nucleic acid nanostructures as carriers of anticancer drugs at the animal level
In other words, there is no research to prove whether nucleic acid nanostructures as carriers of anti-tumor drugs can promote the enrichment of anti-tumor drugs in tumor tissues and whether they can significantly reduce the systemic toxicity of anti-tumor drugs to animals

Method used

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  • Nucleic acid nano structure for carrying antitumor drugs, preparation method and applications thereof
  • Nucleic acid nano structure for carrying antitumor drugs, preparation method and applications thereof
  • Nucleic acid nano structure for carrying antitumor drugs, preparation method and applications thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0054] Example 1 Preparation of nucleic acid nanostructures and drug-loaded nucleic acid nanostructures

[0055] Mix 50 μL of M13 bacteriophage genomic DNA with a final concentration of 5 nM and 100 μL of staple strand mixed solution with a final concentration of 50 nM in 1 mL of 1×TAE / Mg 2+ (pH=8.0) solution, starting from 95°C, gradually cooling down to 20°C and annealing for 12-24 hours to prepare nucleic acid nanostructures with pre-designed geometric shapes.

[0056] Add 1mL of 5mM doxorubicin solution into 1mL of 5nM nucleic acid nanostructure solution, mix well, and incubate with shaking for 24h at 22-28°C and 70rpm to load doxorubicin.

[0057] Centrifuge the mixed solution loaded with doxorubicin at 7000-8000 rpm for 10-15 minutes at 22-28°C to remove unloaded doxorubicin in the supernatant to obtain nucleic acid nanostructures loaded with doxorubicin. For the unloaded doxorubicin content in the supernatant, use the following formula to calculate and determine the lo...

Embodiment 2

[0060] The inhibitory effect of embodiment 2 drug-loaded nucleic acid nanostructures on MDA-MB-231 cell proliferation

[0061] Cultivate MDA-MB-231 cells to the logarithmic growth phase, digest with trypsin, collect the cells, and adjust the concentration of the cell suspension to 5×10 4 cells / mL, inoculate a 96-well plate, 100 μL per well. The 96-well plate was cultured overnight in a carbon dioxide incubator, the culture solution was sucked out, and drug-loaded nucleic acid nanostructures of different concentrations (doxorubicin 0.01, 0.1, 1, 10, 100 μM) were added, and each concentration group had 5 replicate wells. Another 5 groups were added with different concentrations (0.01, 0.1, 1, 10, 100 μM) of doxorubicin. Another group was set as the blank control group (inoculated with cells, no drug added). The MDA-MB-231 cells that had been treated with drugs were continued to be cultured in the incubator for 24 h, the drug-containing medium was discarded, and 0.5 mg / mL of CC...

Embodiment 3

[0064] Example 3 Targeted enrichment of drug-loaded nucleic acid nanostructures in tumor tissue

[0065] Cultivate MDA-MB-231 cells to the logarithmic growth phase, digest with trypsin, collect the cells, and adjust the concentration of the cell suspension to 1×10 7 100 μL was orthotopically inoculated into the lower right breast of 5-6 week old female BALB / c nude mice to model orthotopic mammary gland xenograft tumors per mL. After modeling for 1 week, they were divided into 3 groups for drug administration, namely the normal saline group, the doxorubicin group (doxorubicin 6mg / kg / day), and the drug-loaded nucleic acid nanostructure group (that is, the nucleic acid loaded with doxorubicin). Nanostructure, the administration content is equivalent to doxorubicin 6mg / kg / day, nucleic acid nanostructure 0.071mg / kg / day), intravenous injection of drugs. After 24 hours, the tumor was removed for frozen section, and the red fluorescence of the drug in the tumor tissue section was obs...

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Abstract

The invention discloses a nucleic acid nano structure for carrying antitumor drugs, a preparation method and applications thereof. The nucleic acid nano structure is a random two-dimensional and / or three-dimensional nano structure constructed through a DNA origami technology. The nucleic acid nano structure is obtained through self-assembly between a scaffold chain and a staple chain for auxiliary folding, wherein the scaffold chain and the stable chain are hybridized according to the base paring principle. The provided nucleic acid nano structure taken as the carrier of antitumor drugs can guarantee the antitumor activity of the carried antitumor drugs, and further improves the targeting property of the antitumor drugs. Thus the antitumor drugs can be enriched in the tumor tissues, and the overall toxicity due to the non-specificity of the antitumor drugs is greatly reduced. Furthermore, the preparation method has the advantages of simple technology, low cost, convenience, and easy application.

Description

technical field [0001] The invention relates to the technical field of drug carriers, in particular, the invention relates to a nucleic acid nanostructure for carrying antitumor drugs and its preparation method and application. Background technique [0002] Malignant tumor is an important disease that seriously endangers human health. The lack of specificity of small-molecule anti-tumor drugs leads to severe side effects during chemotherapy, which often leads to the failure of chemotherapy. The key to solving this problem is to develop drug delivery systems for targeted delivery and controlled release of antitumor drugs using nanotechnology, which has become a hot spot in the field of cancer treatment research. [0003] The research on using nanoparticles as anti-tumor drug carriers for anti-tumor therapy began in the 1950s, and there are many researches such as polymer nanomaterials, liposomes or gold nanoparticles. A large number of nanoparticles have been successfully u...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K47/26B82Y5/00A61P35/00
Inventor 丁宝全蒋乔王金业杜洋张倩
Owner THE NAT CENT FOR NANOSCI & TECH NCNST OF CHINA
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