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Ferroferromagnetic nanomaterial producing nitric oxide, preparation method and application

A technology of ferroferric oxide and nanomaterials, applied in the direction of nanotechnology, nanotechnology, nanomedicine, etc., can solve the problems of low accumulation efficiency of nanoparticles and insufficient effect of magnetothermal treatment, and achieve enhanced delivery and accumulation, increased concentration, normalizing effect

Active Publication Date: 2021-12-07
SICHUAN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, it also has the problem of low delivery and accumulation efficiency of nanoparticles at the tumor site, resulting in insufficient effect of magnetothermal therapy.

Method used

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  • Ferroferromagnetic nanomaterial producing nitric oxide, preparation method and application
  • Ferroferromagnetic nanomaterial producing nitric oxide, preparation method and application
  • Ferroferromagnetic nanomaterial producing nitric oxide, preparation method and application

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Experimental program
Comparison scheme
Effect test

Embodiment 1

[0040] The preparation method of the magnetic nanomaterial (Fe-Arg-GOX) modified with an L-type arginine and glucose oxidase on the surface comprises the following steps:

[0041] Step 1: connect the first reactive group with amino on the surface of ferric oxide to obtain surface aminated ferric oxide (Fe-NH 2 ).

[0042] Process such as figure 1 As shown, 50mg of Fe 3 o 4 (average particle diameter of 20 nm) was dispersed in methanol to obtain solution A, and 300 mg of dopamine (DA) was dissolved in methanol to obtain solution B. Solution B was slowly added to solution A under nitrogen protection, and mechanically stirred for 24 hours. After the reaction was completed, methanol was removed by magnetic separation, and the obtained precipitate was repeatedly washed with methanol three times, and dried in vacuum for 12 hours. Obtain surface aminated ferric oxide (Fe-NH 2 ) solid black powder. Step 2: The first reactive group connects an arginine (Fe-Arg).

[0043] Proces...

Embodiment 2

[0048] The preparation method of the magnetic nanomaterial modified with two L-type arginines and glucose oxidase on the surface comprises the following steps:

[0049] Step 1: connect the first reactive group with amino on the surface of ferric oxide to obtain surface aminated ferric oxide (Fe-NH 2 ); Process is with embodiment 1.

[0050] Step 2: Prepare double-protected arginine (Dual-BOC-Arg(Pbf)-OMe);

[0051] Process such as image 3 As indicated, 1.00 g (4.3 mmol, 1 eq) of L-lysine methyl ester hydrochloride (H-Lys-OMe.2HCl) was weighed and dissolved in 20 mL of N,N-dimethylformamide (DMF). After thorough stirring, 1.67g (12.9mmol, 3.0eq) of N,N-diisopropylethylamine (DIEA) was added to the L-lysine methyl ester hydrochloride solution.

[0052] Dissolve 5.00g (9.5mmol, 2.2eq) of the compound Boc-Arg(Pbf)-OH in 20mL of DMF. After fully dissolving, mix and stir with the above-mentioned L-lysine methyl ester hydrochloride solution. Weigh 4.14g (12.9mmol, 3eq) of O-benz...

Embodiment 3

[0062] The preparation method of the magnetic nanomaterial modified by connecting an L-arginine and β-lapachone on the surface through a disulfide bond comprises the following steps:

[0063] Step 1: Sulfhydrylation (Fe-SS) of ferric oxide with carboxyl groups on the surface.

[0064] 50mg of Fe 3 o 4 (average particle diameter of 20 nm) was dispersed in methanol to obtain solution A, and 300 mg of 3-(3,4-dihydroxyphenyl)propionic acid (DPA) was dissolved in methanol to obtain solution B. Solution B was slowly added to solution A under nitrogen protection, and mechanically stirred for 24 hours. After the reaction was completed, methanol was removed by magnetic separation, and the obtained precipitate was repeatedly washed with methanol three times, and dried in vacuum for 12 hours. 64 mg of solid black powder of ferric iron tetroxide (Fe-COOH) with carboxyl groups on the surface was obtained.

[0065] Process such as Figure 6 As indicated, 50 mg of ferric oxide (Fe-COOH)...

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Abstract

The invention discloses ferroferric oxide magnetic nanomaterials for producing nitric oxide, a preparation method and applications. The nanomaterials include a ferroferric oxide inner core, and a first reactive group with amino groups is connected to the surface of the ferric ferric oxide inner core; A reactive group is linked to one or two arginines; the surface of arginine is linked to a catalyst; the catalyst can catalyze excess small molecules in tumor cells to generate hydrogen peroxide; the present invention can catalyze excess small molecules (glucose, NADPH, etc.) in tumor cells through the catalyst etc.) to produce hydrogen peroxide, hydrogen peroxide reacts with L-arginine distributed on the surface of the ferric oxide core to generate nitric oxide, thereby increasing the concentration of nitric oxide in the tumor site, increasing the vasodilation of the tumor site, and promoting tumor vascular The normalization of NPs can enhance the delivery and accumulation of nanoparticles in tumor sites, thereby enhancing the effect of tumor magnetothermal therapy.

Description

technical field [0001] The invention relates to the technical field of biomaterials, in particular to a ferroferromagnetic nanometer material producing nitric oxide, a preparation method and an application. Background technique [0002] Magnetothermal tumor therapy mediated by iron oxide magnetic nanoparticles has good clinical application prospects. It can effectively target and locate tumor tissue through the action of external alternating magnetic field. After local heating, tumor cells are different from normal cells in thermal sensitivity. Induces tumor cell killing. After removing the external magnetic field, the magnetic nanoparticles can be cleared by the endothelial reticular system through the blood circulation. This therapy has shown good efficacy and low side effects in a large number of preliminary clinical trials, and is defined as an emerging "green therapy" by the international medical community. However, its effectiveness largely depends on the concentrati...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K41/00A61K47/54A61K47/62A61K47/69A61P35/00B82Y5/00B82Y40/00
CPCA61K41/0052A61K47/541A61K47/542A61K47/62A61K47/6929A61K47/6931A61P35/00B82Y5/00B82Y40/00
Inventor 聂宇胡傲金蓉蓉
Owner SICHUAN UNIV