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Super-paramagnetic iron oxide nanoparticle compound as well as preparation method and application thereof

An iron oxide nano-particle complex technology, applied in the fields of nano-drugs, nano-technology, nano-technology, etc., can solve the problems of the degree of progression of difficult kidney disease, dynamic evaluation of treatment effect, massive bleeding, sepsis, and unacceptable patients, etc. The effect of low production cost, simple production process and uniform size

Inactive Publication Date: 2016-03-23
ZHEJIANG UNIV
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  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0003] At present, in order to clarify the diagnosis of glomerulonephritis, evaluate the prognosis, formulate the treatment plan and evaluate the curative effect, in most cases, biopsy is required to obtain pathological specimens, but because the biopsy is an interventional and traumatic examination, it may sometimes lead to bleeding , infection, and even serious complications such as hemorrhage and sepsis, some patients find it difficult to accept
In addition, needle biopsy is also difficult to dynamically evaluate the progress of renal lesions and treatment effects.

Method used

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  • Super-paramagnetic iron oxide nanoparticle compound as well as preparation method and application thereof
  • Super-paramagnetic iron oxide nanoparticle compound as well as preparation method and application thereof
  • Super-paramagnetic iron oxide nanoparticle compound as well as preparation method and application thereof

Examples

Experimental program
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Effect test

Embodiment 1

[0026] Embodiment 1 superparamagnetic iron oxide nanoparticles

[0027] Add 0.9 mmol of iron triacetylacetonate and 0.9 mmol of carboxymethylated methoxypolyethylene glycol to 20 ml of analytically pure 2-pyrrolidone solution, and blow nitrogen gas for 30 minutes. After completion, the mixture was heated at 200°C for 30 minutes, then changed to 240°C for 40 minutes. After the reaction, the mixed product was cooled at room temperature, and 100 ml of diethyl ether / acetone (volume ratio 5:1) mixed solution was slowly added until precipitation was precipitated. After centrifugation, the precipitated black precipitate was washed with pure water and vacuum-dried to obtain superparamagnetic iron oxide nanoparticles with a particle size of 25.3±1.5nm. TEM images and magnetic saturation images ( figure 1 ) showed that the nanoparticles were fine-grained and uniform in size ( figure 1Middle A); The saturation magnetization is 66.02emu / mg ( figure 1 Middle B).

Embodiment 2

[0028] Example 2 Synthesis of MR Molecular Imaging Probes

[0029] Take 1 mg of the superparamagnetic iron oxide nanoparticles obtained in Example 1 (calculated based on iron content), add boric acid buffer solution (pH value 9, 0.5 ml), and shake at room temperature (25° C.) for 10 min. Then add 1 mg 1-ethyl-(3-dimethylaminopropyl) carbodiimide hydrochloride (EDC HCL), 0.5 mg N-hydroxysulfosuccinimide (NHS), shake at 37 ° C for 30 min , adding 0.2 mg of rabbit anti-rat anti-IL-1 antibody (purchased from Beijing Boaosen) and gently shaking at 37° C. for 3 h. After the end, rinse the tube wall with phosphate buffer (pH 7.4), dilute the above liquid in phosphate buffer, and use an ultrafiltration centrifuge tube to centrifuge three times at 4°C and 3000 rpm for 30 minutes each time to remove unbound free antibody. After centrifugation, use a pipette gun to suck out the precipitate and dissolve it in a phosphate buffer with a pH value of 7.4, and adjust the concentration to 1 m...

Embodiment 3

[0030] Example 3 MR Molecular Imaging of Normal Rats and Chronic Glomerulonephritis Rats

[0031] The rat model of mesangial proliferative nephritis adopts the anti-Thy-1 antibody induction method commonly used in the world, and the modeling process is as follows: male rats are injected with anti-Thy-1 monoclonal antibody OX-7 (1mg / kg) separately through the tail vein, On the 7th day, the model was successfully produced. Then normal male SD rats and male mesangial proliferative nephritis rat models were used for in vivo MR imaging. The MR imaging system is German Bruker7.0Tmicro-MR, the inner diameter of the horizontal scanning frame is 16cm, and the rat head coil of 38mm is used. After being anesthetized with 4% isoflurane, the mice were placed in a plexiglass scanning bed, and the brains of the mice were fixed with braces and ear bars. Anesthesia was maintained with 1.5% isoflurane: air mixture, and heart rate and respiration were monitored. The scanning range covers both...

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Abstract

The invention discloses a super-paramagnetic iron oxide nanoparticle compound as well as a preparation method and application thereof. The super-paramagnetic iron oxide nanoparticle compound is prepared by the following steps: preparing super-paramagnetic iron oxide nanoparticles by taking Fe3O4 with surface modified with a polyethylene glycol derivative as a core; and then modifying an IL-1 antibody on the surfaces of the super-paramagnetic iron oxide nanoparticles, so that the super-paramagnetic iron oxide nanoparticle compound is prepared. The super-paramagnetic iron oxide nanoparticle compound prepared by the invention can achieve specific affinity with high-expression IL-1 in mesangial area and glomerular area of chronic glomerulonephritis in vivo and can display and quantify the early lesions of the chronic glomerulonephritis in the forms of magnetic resonance images and data; therefore, the super-paramagnetic iron oxide nanoparticle compound can be used for the early diagnosis of diseases and for the dynamic monitoring of changes of nephropathy, and a magnetic resonance molecular imaging means for noninvasive and in vivo evaluation of membranous nephropathy is provided.

Description

(1) Technical field [0001] The invention relates to a magnetic resonance contrast agent, in particular to a preparation and application method of a targeted superparamagnetic nanometer molecular probe specifically labeled with interleukin-1 (IL-1). (2) Background technology [0002] Chronic glomerulonephritis is the main cause of nephrotic syndrome in adults. Existing studies have proved that various inflammatory mediators play an important role in the process of immunological damage in glomerulonephritis, among which interleukin-1 (interleukin-1 , IL-1) play a unique role. Interleukins refer to cytokines that mediate the interaction between white blood cells or immune cells, which can activate and regulate immune cells, mediate the activation, proliferation and differentiation of immune cells. Among more than thirty kinds of interleukins discovered so far, IL-1 has been proved to be a key factor of inflammatory response. IL-1 is not expressed in normal glomerulus, but its...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K49/18A61K49/16A61K49/12B82Y5/00B82Y15/00
CPCA61K49/16A61K49/12A61K49/1818B82Y5/00B82Y15/00
Inventor 肖文波黄强文颂汪启东过川根张瑞杨荣
Owner ZHEJIANG UNIV
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