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Nucleic acid nano structure carrier-precious metal photosensitive contrast agent composite for living organism photo-acoustic imaging, preparation method and applications thereof

A nucleic acid nanometer and precious metal technology, which is applied to preparations for in vivo tests, medical preparations without active ingredients, and medical preparations containing active ingredients, etc., to achieve the effect of high-sensitivity photoacoustic imaging capabilities

Inactive Publication Date: 2015-02-04
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

In other words, there is no research to date to prove whether nucleic acid nanostructures as carriers of noble metal photosensitive components can promote the enrichment of photosensitive components in tumor tissues for more effective in vivo photoacoustic imaging.

Method used

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  • Nucleic acid nano structure carrier-precious metal photosensitive contrast agent composite for living organism photo-acoustic imaging, preparation method and applications thereof
  • Nucleic acid nano structure carrier-precious metal photosensitive contrast agent composite for living organism photo-acoustic imaging, preparation method and applications thereof
  • Nucleic acid nano structure carrier-precious metal photosensitive contrast agent composite for living organism photo-acoustic imaging, preparation method and applications thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0062] Example 1 Preparation of nucleic acid nanostructure carrier, noble metal photosensitive contrast agent and nucleic acid nanostructure carrier-noble metal photosensitive contrast agent complex

[0063] Mix 50 μL of M13 phage genomic DNA with a final concentration of 5 nM and 100 μL of staple strand and capture strand with a final concentration of 50 nM in 1 mL of 1×TAE / Mg 2+ (pH=8.0) solution, starting from 95° C., annealing at 20° C. gradually, annealing incubation time is 12-24 hours, and preparing a nucleic acid nanostructure with a pre-designed geometric shape. The triangular DNA origami used in this experiment was modified based on Rothemund's 2006 design (Nature, 2006, 440, 297-302.), and the capture strand was extended at 7 positions (5'-AAAAAAAAAAAAAAAA-original staple strand sequence -3'), its capture sequence is complementary to the sequence used by subsequent DNA modification gold rods.

[0064] Regulation of AgNO by seed-induced growth method using cetyltrim...

Embodiment 2

[0075] Example 2 Living Cell Uptake of Nucleic Acid Nanostructure-Gold Nanorod Complex

[0076] Mouse breast cancer 4T1 cells were seeded at 100mm 2 In a petri dish, use RPMI1640 medium (10% fetal bovine serum and double antibody) in 5% CO 2 Incubator, cultivate at 37°C. When the cells grow to about 80% confluence, digest the cells and inoculate in 35mm 2 The confocal small dishes were cultured overnight, and gold rods, DNA origami-gold nanorod composite structures (0.1 nM, diluted in complete medium) and the control group were added and incubated for 24 hours. The drug solution of each group was discarded, the cells were washed with PBS, and then observed with a two-photon fluorescence microscope with an excitation wavelength of 800 nm.

[0077] Observation results such as image 3 As shown, the pictures from top to bottom are the control group, the gold nanorod treatment group and the DNA origami-gold nanorod composite structure treatment group respectively, and from lef...

Embodiment 3

[0078] Example 3 In vivo photoacoustic imaging of nucleic acid nanostructure-gold nanorod complexes

[0079] Culture 4T1 cells to the logarithmic growth phase, digest with trypsin, collect the cells, adjust the concentration of the cell suspension to 1×10 7100 μL was orthotopically inoculated subcutaneously on the back of 5-6 week old female BALB / c nude mice to model subcutaneous mammary gland xenografts. After 1 week of modeling, when the tumor size reaches 100mm 3 , divided into two groups for administration treatment, namely the gold nanorod group (3nM×150 μL), the nucleic acid nanostructure-gold nanorod complex group (3nM×150 μL), and the drugs were injected intravenously. At 0, 3, and 24 hours after injection, in vivo photoacoustic imaging was performed on tumor-bearing mice using a small animal photoacoustic imaging system.

[0080] Figure 4 Shown are the photoacoustic imaging results of tumor-bearing mice at 0h, 3h and 24h after injection of gold rods. Depend on ...

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Abstract

The invention discloses a nucleic acid nano structure carrier, a nucleic acid nano structure carrier-precious metal photosensitive contrast agent composite comprising the same, and preparation methods and applications of the carrier and the composite. The nucleic acid nano structure is a random two-dimensional and / or three-dimensional nano structure constructed by a DNA paper-folding technology. The precious metal components are used to carry out DNA modification on the surface of the carrier and selected from one or more of gold nano rods, gold nano shells, silver-coated gold nano rods, and gold nano cages. The provided composite is used as a photo-acoustic imaging probe, is capable of guaranteeing the absorption contrast enhancing effect of the photo-acoustic contrast agent which is coupled to the composite, and moreover can prominently improve the targeting performance of the contrast agent on tumors. Furthermore, the precious metal photosensitive components which are coupled to the carrier are enriched in the inner of tumor tissues, and thus the solved is the problems that conventional contrast agent is distributed over the whole human body or the contrast agent can only stay on the tumor surfaces. The preparation method has the advantages of simple technology, low cost, convenience, and easy application.

Description

technical field [0001] The invention belongs to the field of photoacoustic imaging, and relates to a nucleic acid nanostructure carrier, a nucleic acid nanostructure carrier-noble metal photosensitive contrast agent complex containing it, and their preparation methods and applications. A nucleic acid nanostructure carrier for photoacoustic imaging, a nucleic acid nanostructure carrier-noble metal photosensitive contrast agent complex containing the nucleic acid nanostructure carrier, their preparation method and application. Background technique [0002] Malignant tumor is an important disease that seriously endangers human health. In the face of the rising incidence and mortality of tumors worldwide, as well as the limitations of current diagnosis and treatment methods, the development of an integrated diagnosis and treatment solution with high efficiency and low toxicity has become an urgent and major issue. How to effectively transport molecular imaging reagents for earl...

Claims

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Application Information

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IPC IPC(8): A61K41/00A61K49/00A61K47/30A61K47/02A61K45/00A61P35/00
Inventor 丁宝全蒋乔苏晓芳宋琳琳杜洋张倩
Owner THE NAT CENT FOR NANOSCI & TECH NCNST OF CHINA
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