Targeting light-operated nitric oxide release nanometer composite material medicine system and preparation method thereof

A nanocomposite material and drug technology, applied in the field of multifunctional nanocomposite drug system and its preparation

Active Publication Date: 2014-12-10
EAST CHINA UNIV OF SCI & TECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The above-mentioned metal nitrosyl donors can release NO in vivo through the control of external light, but how to selectively release the appropriate concentration of NO in a specific area or in a specific cell is still facing challenges.

Method used

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  • Targeting light-operated nitric oxide release nanometer composite material medicine system and preparation method thereof
  • Targeting light-operated nitric oxide release nanometer composite material medicine system and preparation method thereof
  • Targeting light-operated nitric oxide release nanometer composite material medicine system and preparation method thereof

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preparation example Construction

[0096] The present invention also provides a preparation method of the pharmaceutical system of the present invention, which generally includes the following steps:

[0097] (1) Provide exogenous NO donors, targeting groups and carrier nanoparticles;

[0098] (2) Covalently loading the exogenous NO donor, the targeting group and the carrier nanoparticles to form the NO nanocomposite drug system.

[0099] In another preferred example, in step (1), the exogenous NO donor includes a metal nitrosyl compound [(tpy')M(R 1 )(NO)](PF 6 ) 3 , tpy' is 4'-formic acid-2,2':6',2"-terpyridine, M is metal ruthenium (Ru) or metal manganese (Mn), R 1 For DAMBO (boron dipyrrole methyl derivatives) or o-phenylenediamine.

[0100] In another preferred example, the carrier nanoparticles are surface aminated nanoparticles.

[0101] In another preferred example, the targeting group is selected from: folic acid molecule, galactose molecule, biotin, or a combination thereof.

[0102] In another ...

Embodiment 1

[0109] The nitrosyl compound of embodiment 1 metal Ru [(tpy COOH )Ru(DAMBO)(NO)](PF 6 ) 3 Synthesis

[0110] (1)[(tpy COOH )Ru(DAMBO)(Cl)](PF 6 ) synthesis (tpy COOH for 4'-formic acid-2,2':6',2"-terpyridine):

[0111] Add Ru(tpy COOH ) Cl 3 (150mg, 0.31mmol), DAMBO (117mg, 0.33mmol), LiCl (5mg, 2.0mmol) and Et 3 N0.4mL, vacuumize and nitrogen three times respectively, add 40mL of EtOH / H 2 O(3:1, v / v), in N 2 Reflux in the atmosphere for 8 hours, suction filter while hot, and concentrate the dark red filtrate to several milliliters. After cooling to room temperature, add excess saturated NH 4 PF 6 solution, and the mixture was placed in a refrigerator at 5°C overnight. The reddish-brown precipitate was filtered out and washed with H 2 O and Et 2 O were washed three times, respectively, and dried in vacuo. 182.3 mg of the target product was obtained with a yield of 64%.

[0112] (2)[(tpy COOH )Ru(DAMBO)(NO 2 )](PF 6 )Synthesis:

[0113] Will [(tpy COOH )Ru(...

Embodiment 2

[0117] Embodiment 2 nanoparticle composite drug system {Ru-NOTiO 2}Synthesis

[0118] (1) NH 2 TiO 2 (surface aminated TiO 2 Nanoparticles) Preparation

[0119] In a 50mL round bottom flask, add 9.3mg (4-NH 2 )-C 6 h 4 -PO 3 After H, add 2 mL of pH9 aqueous solution, and after the solid dissolves, add 18 mL of TiO 2 The dispersed aqueous solution of the above solution was added to the above solution, and the mixed solution was stirred overnight at room temperature, and the obtained dispersion was centrifuged at 1000 rpm for 10 minutes, the supernatant was removed, and the nanoparticles were washed twice with water to obtain the surface aminated TiO 2 Nanoparticles, redispersed in aqueous solution, ready to use.

[0120] (2) Nanoparticle composite drug system {Ru-NOTiO 2} preparation

[0121] Will [(tpy COOH )Ru(DAMBO)(NO)](PF 6 ) 3 (100mg, 0.08mmol) and FA (folic acid) (5.0mg, 0.01mmol) were dissolved in 5mL of DMF, added EDC / NHS activation for 30 minutes, after ...

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Abstract

The invention provides a preparation method for a multifunctional nanometer medicine system with the functions of fluorescence tracing, targeting conveying and intracellular light-operated release of nitric oxide. The nanometer system takes titanium dioxide nanoparticle, carbon quantum dot, graphene quantum dot or the like as a carrier, takes metal ruthenium and manganese nitrosyl compounds as exogenous NO donors, and takes folic acid, galactose molecules and the like as targeting guiding groups. The nitric oxide release nanometer system has good biological compatibility and stability, has fluorescence tracing function, is capable of performing nitric oxide selective light-operated release on specific cancer cells, and has potential application prospect and commercial business in the fields of treatment, photodynamic therapy (PDT) and the like on diseases caused by lack of NO in body.

Description

technical field [0001] The invention relates to the field of inorganic nano medicines. Specifically, the present invention provides a multifunctional nanocomposite drug system with fluorescent tracer, targeted delivery, and intracellular light-controlled delivery of nitric oxide and a preparation method thereof. Background technique [0002] Nitric oxide (NO) is an endogenous biological small molecule that plays a very important role in many physiological processes, such as regulating blood pressure, immune and inflammatory responses, nerve conduction, and cell apoptosis. The biological function of NO depends on the location, time and dose of its release in the organism. Low concentration (nmolL -1 ) NO promotes cell growth, while high concentration (μmolL -1 -mmolL -1 ) will lead to cell apoptosis. NO is a free radical gas, easily reacts with oxygen, is extremely unstable, and has a short half-life. Although NO has many biological regulation functions, its application...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K9/14A61K47/48A61K33/42A61K41/00A61P9/00A61P37/02A61P29/00
Inventor 刘劲刚向慧静唐伟伟邓乔
Owner EAST CHINA UNIV OF SCI & TECH
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