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Preparation method and application of single-atom gadolinium contrast agent supported on hollow nitrogen-doped carbon spheres

A nitrogen-doped carbon, contrast agent technology, applied in nuclear magnetic resonance/magnetic resonance imaging contrast agents, preparations for in vivo experiments, pharmaceutical formulations, etc. Safety, weak tumor enrichment and other issues, to achieve the effect of enhancing tumor imaging performance, preventing gadolinium ion leakage, and improving biological safety

Active Publication Date: 2022-05-17
BEIJING INSTITUTE OF TECHNOLOGYGY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, commercially available gadolinium metal chelates are small molecules with fast metabolism and short retention time in the body. Due to their distribution throughout the body, they have no targeting and weak tumor accumulation.
Commercial gadolinium metal chelates are unstable in acidic environments, and there is a risk of gadolinium ion shedding, and free gadolinium ions can cause renal fibrosis, which limits the application and application of gadolinium chelate contrast agents in MRI-enhanced imaging. biosecurity
[0003] The development of gadolinium-based nanomaterials provides an idea to solve the problems of small-molecule gadolinium metal chelates. However, synthetic gadolinium-based nanomaterial contrast agents with good biocompatibility, strong contrast enhancement effect and tumor targeting are still a challenge. big challenge
At the same time, because the gadolinium atoms inside the nanomaterials cannot fully contact with water molecules, they cannot fully exert their enhancement effect on the relaxation efficiency of water protons.

Method used

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  • Preparation method and application of single-atom gadolinium contrast agent supported on hollow nitrogen-doped carbon spheres
  • Preparation method and application of single-atom gadolinium contrast agent supported on hollow nitrogen-doped carbon spheres
  • Preparation method and application of single-atom gadolinium contrast agent supported on hollow nitrogen-doped carbon spheres

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preparation example Construction

[0037] The preparation of hollow nitrogen-doped carbon sphere-supported single-atom contrast agent specifically includes the following steps:

[0038] S1. After mixing ammonia water and ethanol, add silica precursor to react, centrifuge and dry to obtain nano silica powder;

[0039]Wherein, the ammoniacal liquor concentration is 25~28wt.%, the volume ratio of ammoniacal liquor, ethanol and silicon dioxide precursor is 1:(10~12):0.2; Silicon dioxide precursor is orthosilicate ethyl ester; In this step The reaction temperature range for preparing silicon dioxide powder is 40-60°C, and the size of silicon dioxide can be adjusted by changing the reaction temperature. As the temperature increases, the particle size of the prepared nano-silica becomes smaller; when the reaction temperature is 40, 50 and 60°C, the particle size of the silicon dioxide is 130, 90 and 60nm respectively.

[0040] S2, ultrasonically dispersing the nano-silica powder prepared in step S1 in a tris buffer s...

Embodiment 1

[0051] Please refer to figure 1 As shown, this embodiment is a preparation method of a single-atom gadolinium contrast agent supported on hollow nitrogen-doped carbon spheres with a particle size of 90 nm, which is prepared by the following steps:

[0052] (1) Preparation of nano-silica microspheres: Mix 162mL of absolute ethanol and 15mL of ammonia water into a 250mL single-necked flask, place it in a water bath at 50°C, stir and heat, and add 2.8mL of orthosilicon dropwise after ten minutes Ethyl Oxide (TEOS) and keep the reaction at this temperature for one hour. After the reaction, centrifuge at 9000rpm for 8 minutes, discard the supernatant, wash with ethanol three times, and dry in a vacuum oven at 60°C for later use.

[0053] (2) Preparation of polydopamine (PDA)-coated nano-silica microspheres: disperse 100 mg of prepared nano-silica microspheres in 40 mL of deionized water, add 48 mg of tris, and vigorously sonicate for 30 minutes After stirring in a 100mL single-ne...

Embodiment 2

[0062] A hollow nitrogen-doped carbon sphere with a particle size of 70 nm supports a monoatomic gadolinium contrast agent. Compared with Example 1, the difference is that the preparation temperature of nano-silica microspheres in step (1) is changed from 50 ° C to into 60°C. Others are substantially the same as in Embodiment 1, and will not be repeated here.

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Abstract

The invention provides a preparation method and application of a single-atom gadolinium contrast agent supported by hollow nitrogen-doped carbon spheres. The method prepares size-controllable nano-silica microspheres as a template, simultaneously coats dopamine and gadolinium ions on the surface of nano-silica microspheres, and obtains nitrogen-doped carbon-supported single-atom gadolinium through high-temperature calcination; then The silicon dioxide is etched away, and the surface is coated with a hydrophilic polymer to obtain a PEGylated hollow nitrogen-doped carbon sphere loaded monoatomic gadolinium contrast agent. Through the above method, the unique Gd-N-C structure of the present invention can make the monoatomic gadolinium anchored stably by the nitrogen atom without falling off, which improves the biological safety, and the polyethylene glycol coated on the surface further improves its water solubility and biocompatibility; the single-atom contrast agent can make full use of each gadolinium atom, which improves the utilization rate of metal atoms; it has excellent contrast imaging ability and effect, and is a new type of contrast agent with wide application and good prospects.

Description

technical field [0001] The invention relates to the technical field of contrast agent preparation, in particular to a preparation method and application of a single-atom gadolinium contrast agent supported on hollow nitrogen-doped carbon spheres. Background technique [0002] Magnetic resonance imaging is a non-invasive disease diagnosis method widely used in clinical practice. It has the advantages of high spatial resolution, good deep tissue and soft tissue imaging effect, safety and high efficiency. In order to further improve the contrast and sensitivity of MRI, gadolinium-based MRI contrast agents are widely used to enhance T 1 MRI effects. Gadolinium element has seven unpaired electrons arranged in the same direction, which can effectively reduce the relaxation time of water protons in the detected tissue, and has a significant enhancement performance of nuclear magnetic resonance imaging. More than one-third of MRI scans use commercially available gadolinium metal c...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K49/08A61K49/12A61K49/18
CPCA61K49/08A61K49/183A61K49/126
Inventor 戎宏盼刘山歌张加涛易宇
Owner BEIJING INSTITUTE OF TECHNOLOGYGY
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