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Lymph targeted prussian blue analog nano-particle and preparation method thereof

A technology similar to Prussian blue and lymphatic targeting, applied in the field of biomedical materials, can solve the problems of biological toxicity, easy damage of organic layer, insufficient signal, etc., achieve good biocompatibility, improve the stability of imaging signals, and operate simple and easy effects

Active Publication Date: 2016-04-13
SHENZHEN INST OF ADVANCED TECH CHINESE ACAD OF SCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0006] However, the magnetic resonance imaging signal of the current Prussian blue nanoparticles is insufficient. Most of the research on the protection and modification of Prussian blue nanoparticles currently uses non-water-soluble organic substances, while the Prussian blue nanoparticles wrapped by water-soluble organic substances use electrostatic The method of adsorption, the organic layer of the obtained product is easily destroyed under physiological conditions in the body, forming bare Prussian blue nanoparticles, which are insoluble in water environment and are easily removed by the body. At the same time, the metal ions in the physiological salt Prone to substitution reaction with naked Prussian blue, potentially toxic to organisms

Method used

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  • Lymph targeted prussian blue analog nano-particle and preparation method thereof

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Embodiment 1

[0036] This embodiment provides a method for preparing lymphoid-targeted Prussian blue-like nanoparticles, comprising the following steps:

[0037] (1) Dissolve hyaluronic acid with a molecular weight of 10,000 in MES buffer solution, mix and stir evenly, and prepare solution A, wherein, each milliliter of solution A contains 1 mg of hyaluronic acid, take 50 mL of solution A, and Slowly add 200 mg of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride and 300 mg of N-hydroxysuccinimide under stirring condition, react for 15 min, and adjust the pH value to 7. Then add 3 mL of ethylenediamine, react for 24 hours, and then dialyze with deionized water to obtain product E.

[0038] (2) Diethylenetriaminepentaacetic acid is dissolved in the buffer solution, after mixing and stirring evenly, be mixed with B solution, wherein, every milliliter of B solution contains the diethylenetriaminepentaacetic acid of 1mg, get the B solution of 50mL, in Slowly add 200 mg of 1-(3-dimeth...

Embodiment 2

[0044] This embodiment provides a method for preparing lymphoid-targeted Prussian blue-like nanoparticles, comprising the following steps:

[0045] (1) Dissolve hyaluronic acid with a molecular weight of 6800 in TES buffer solution, mix and stir evenly, and prepare solution A, wherein, each milliliter of solution A contains 5 mg of hyaluronic acid, take 50 mL of solution A, and stir Slowly add 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride 1g, N-hydroxysuccinimide 1.5g under conditions, react for 10min, adjust the pH value to 7. Then add 5 mL of ethylenediamine, react for 12 hours, and then dialyze with deionized water to obtain product E.

[0046] (2) Diethylenetriaminepentaacetic acid is dissolved in the TES buffer solution, after mixing and stirring uniformly, it is prepared into solution B, wherein, every milliliter of solution B contains 5 mg of diethylenetriaminepentaacetic acid, and 50 mL of solution B is taken, Slowly add 1-(3-dimethylaminopropyl)-3-ethyl...

Embodiment 3

[0052] This embodiment provides a method for preparing lymphoid-targeted Prussian blue-like nanoparticles, comprising the following steps:

[0053] (1) Dissolve hyaluronic acid with a molecular weight of 30,000 in Tris buffer solution, mix and stir evenly, and prepare solution A, wherein, each milliliter of solution A contains 10 mg of hyaluronic acid, take 50 mL of solution A, and Slowly add 2 g of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride and 3 g of N-hydroxysuccinimide under stirring conditions, react for 30 min, and adjust the pH value to 7. Then add 3 mL of 1,3-propanediamine, react for 48 hours, and dialyze with deionized water to obtain product E.

[0054] (2) Diethylenetriaminepentaacetic acid is dissolved in Tris buffer solution, after mixing and stirring evenly, be mixed with B solution, wherein, every milliliter of B solution contains the diethylenetriaminepentaacetic acid of 10mg, get the B solution of 50mL, Slowly add 2 g of 1-(3-dimethylaminopr...

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Abstract

The invention provides a lymph targeted prussian blue analog nano-particle and a preparation method thereof. According to the method, through crosslinking hyaluronic acid on diethylenetriamine pentaacetic acid and chelating on gadolinium ions, the stable lymph targeted prussian blue analog nano-particle with the hyaluronic acid on the surface is formed. The surface of the nano-particle is coated with the hyaluronic acid, so that prussian blue analog is protected from being affected by a physiological environment, and a lymph targeting effect is achieved; great stability under a physiological condition is realized, and biocompatibility and imaging signal stability are improved; a synthetic reaction is performed under room temperature, and is energy-saving, environment-friendly and simple and practicable in operation; the lymph targeted prussian blue analog nano-particle can serve as a light absorption material, and is higher in light absorption efficiency and better in light stability; the kernel class prussian blue analog nano-particle has more unpaired electrons by using gadolinium to substitute the position of ferric iron, and is stronger in magnetic resonance signal; The surface of the nano-particle is coated with the hyaluronic acid, the hyaluronic acid is one of human tissue composition, and the biocompatibility is very good.

Description

technical field [0001] The invention belongs to the field of biomedical materials, and in particular relates to a lymphatic-targeted Prussian blue-like nanoparticle and a preparation method thereof. Background technique [0002] In recent years, the incidence of cancer has shown an obvious upward trend. Due to its special properties, the application of nanomaterials in the field of biomedicine, especially in the diagnosis and treatment of cancer, has attracted more and more attention. Nanomaterials are expected to solve the limitations of traditional biomedical methods. . However, the current research on nanomaterials is limited to in vitro experiments, and its biological safety in the human body cannot be guaranteed, which severely limits its further development. Solving the biological safety of nanomaterials has become a key issue in the application of nanomaterials in the field of biomedicine. The main biological characteristics of cancer are invasion and metastasis, an...

Claims

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Application Information

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IPC IPC(8): A61K49/18A61K49/12B82Y5/00B82Y15/00A61K49/22
CPCA61K49/0002A61K49/085A61K49/12A61K49/1863A61K49/222B82Y5/00B82Y15/00
Inventor 张华娟宋亮
Owner SHENZHEN INST OF ADVANCED TECH CHINESE ACAD OF SCI
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