Hollow gold nanospheres modified by CpG oligodeoxynucleotide as well as preparation method and applications

An oligodeoxynucleotide and gold nanosphere technology, which is applied in the field of preparation of hollow gold nanosphere materials, can solve the problems of difficulty in permeating through cell membranes, hindering the immune application of ODNs, poor water solubility and stability, etc.

Inactive Publication Date: 2018-09-28
WUHAN UNIV OF SCI & TECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

However, the main channel for CpG ODNs to stimulate cellular responses is cellular uptake, but individual ODNs have poor water solubility and stability, are difficult to penetrate the cell membrane, and are easily cleared by nucleases in serum and cytoplasm, which greatly hinders ODNs immune application

Method used

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  • Hollow gold nanospheres modified by CpG oligodeoxynucleotide as well as preparation method and applications
  • Hollow gold nanospheres modified by CpG oligodeoxynucleotide as well as preparation method and applications
  • Hollow gold nanospheres modified by CpG oligodeoxynucleotide as well as preparation method and applications

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0100] The preparation method of the hollow gold nanosphere (surface plasmon resonance absorption wavelength is 746nm) modified by CpG oligodeoxynucleotide:

[0101] Add 1.0×10 -2 ~2.0mol / L anhydrous sodium citrate solution and 5.0×10 -2 ~10.0mol / L anhydrous cobalt chloride solution. The mixture was deoxygenated under argon for 20-30 minutes. To this solution was quickly added freshly prepared 1.0 x 10 -2 ~6.0mol / L sodium borohydride solution, shake while adding. After 3 to 5 minutes of reaction, inject 1.0×10 -3 ~2.0mol / L citric acid·aqueous solution, shake continuously to fully hydrolyze sodium borohydride. After 10 to 45 minutes, take 20 to 40 mL of cobalt solution and quickly transfer it to an argon-purged measuring cylinder, and then quickly pour it into a 1.0×10 -4 ~1.0mol / L chloroauric acid tri-water solution, continue shaking and keep in argon flow for 50~60 minutes. Then stop deoxygenation, expose the solution to air, and oxidize for 45-60 minutes. Finally, ce...

Embodiment 2

[0107] The preparation method of the hollow gold nanosphere (surface plasmon resonance absorption wavelength is 961nm) modified by CpG oligodeoxynucleotide:

[0108] Add 1.0×10 -2 ~2.0mol / L sodium citrate · two aqueous solution and 5.0×10 -2 ~10.0mol / L cobalt chloride hexaqueous solution. The mixture was deoxygenated under argon for 40-50 minutes. To this solution was quickly added freshly prepared 1.0 x 10 -2 ~6.0mol / L sodium borohydride solution, shake while adding. After 5-7 minutes of reaction, inject 1.0×10 -3 ~2.0mol / L citric acid di-water solution, shake continuously to fully hydrolyze sodium borohydride. After 5 to 10 minutes, take 10 to 30 mL of cobalt solution and quickly transfer it to an argon-purged measuring cylinder, and then quickly pour it into a 1.0×10 -4 ~1.0×10 -2 mol / L chloroauric acid tri-aqueous solution, continue to shake and keep in argon flow for 60-80 minutes. Then stop deoxygenation, expose the solution to air, and oxidize for 30-50 minutes....

Embodiment 3

[0112] The preparation method of the hollow gold nanosphere (surface plasmon resonance absorption wavelength is 806nm) modified by CpG oligodeoxynucleotide:

[0113] Add 1.0×10 -3 ~1.0mol / L sodium citrate · two aqueous solution and 5.0×10 -1 ~5.0mol / L anhydrous cobalt chloride. The mixture was deoxygenated under argon for 50-80 minutes. To this solution was quickly added freshly prepared 1.0 x 10 -2 ~6.0mol / L sodium borohydride solution, shake while adding. After 5-10 minutes of reaction, inject 1.0×10 -3 ~2.0mol / L citric acid·aqueous solution, shake continuously to fully hydrolyze sodium borohydride. After 30 to 60 minutes, take 20 to 40 mL of cobalt solution and quickly transfer it to an argon-purged measuring cylinder, and then quickly pour it into a 1.0×10 -4 ~0.1mol / L chloroauric acid tetra-water solution, continue shaking and keep in argon flow for 50~60 minutes. Then stop deoxygenation, expose the solution to air, and oxidize for 45-80 minutes. Finally, centrifu...

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Abstract

The invention discloses a preparation method and applications of hollow gold nanospheres modified by CpG oligodeoxynucleotide. Cobalt chloride is subjected to reduction by adopting sodium borohydride,thus cobalt nanoparticles are obtained, cobalt nanoparticles are adopted for carrying out reduction on chloroauric acid, and thus hollow gold nanospheres are prepared; CpG oligodeoxynucleotide, a surfactant and a buffer solution are added into a solution of the hollow gold nanospheres, shaking culture is carried out, and thus the hollow gold nanosphere material modified by CpG oligodeoxynucleotide is obtained. According to the technical scheme, by utilizing the property that the hollow gold nanospheres have the large loading capacity, CpG is loaded through the self-assembly effect, the synthesis method is simple, and the method is suitable for large-scale production and application; the cell uptake capacity of CpG oligodeoxynucleotide can be enhanced, and the biocompatibility is good; thehollow gold nanospheres modified by CpG oligodeoxynucleotide have the near-infrared surface plasma adsorbing effect, the primary tumor is eliminated by utilizing the photothermal ablation effect, a tumor antigen is generated in situ, under the promoting of CpG oligodeoxynucleotide, the antitumor immunity of the whole body is induced, and the distant metastasis tumor is further treated.

Description

technical field [0001] The present invention relates to a hollow gold nanosphere material modified by cytosine-phosphate-guanine (CpG) oligodeoxynucleotide, and the present invention also relates to a preparation method of the hollow gold nanosphere material modified by this CpG oligodeoxynucleotide, which A CpG oligodeoxynucleotide-modified hollow gold nanosphere material can be applied to the combined treatment of cancer photothermal therapy and immunotherapy. Background technique [0002] In recent years, the preparation of nanomaterials and their application in cancer therapy have attracted extensive attention. Gold nanomaterials have become commonly used nanomaterials in cancer therapy research due to their good biocompatibility, low toxicity, easy surface modification, and diagnostic and photothermal properties. Some applications of gold nanomaterials are already in clinical trials. Gold nanomaterials include gold nanorods, gold nanocages, solid gold nanoparticles, a...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K41/00A61K39/00A61K39/39A61K47/52A61P35/00
CPCA61K39/0011A61K39/39A61K41/0052A61K47/52A61K2039/55511A61K2039/572A61K2039/575A61P35/00A61K2300/00
Inventor 邹涛罗静程杨龚志伟彭娜刘义
Owner WUHAN UNIV OF SCI & TECH
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