Method for preparing multifunctional manganous manganic oxide nano-particle nuclear magnetic resonance contrast agent mediated by polyethyleneimine

A technology of nanomanganese tetroxide and polyethyleneimine, which is applied in the field of preparation of nuclear magnetic resonance contrast agents, can solve the problems of high cost, interfere with clinical diagnosis, limit clinical application and the like, and achieve high targeting, good water solubility, Easy to operate effect

Inactive Publication Date: 2015-01-14
DONGHUA UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

However, the high cost of gold and silver as precious metals limits its clinical application to a certain extent, while iron oxide nanoparticles are usually used as MRI negative contrast agents.
Because in the human blood, the calcium ion enrichment area, the metal ion deposition and the human tissue damage site are in the T 2 Negative contrast images can also be obtained due to signal attenuation during imaging, which often interferes with clinical diagnosis

Method used

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  • Method for preparing multifunctional manganous manganic oxide nano-particle nuclear magnetic resonance contrast agent mediated by polyethyleneimine
  • Method for preparing multifunctional manganous manganic oxide nano-particle nuclear magnetic resonance contrast agent mediated by polyethyleneimine
  • Method for preparing multifunctional manganous manganic oxide nano-particle nuclear magnetic resonance contrast agent mediated by polyethyleneimine

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Experimental program
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Embodiment 1

[0080] Dissolve 0.150g PEI in 15mL diethylene glycol (DEG), stir at room temperature until uniformly dispersed, then weigh 0.3795g Mn(acac) 2 Put it into the above mixed solution and keep stirring for 1 hour, then transfer the obtained mixture solution into a high-pressure reactor, and react at 180° C. for 24 hours. After the reaction was finished, naturally cool to room temperature, and the obtained black solution was centrifuged at 8000rpm for 5 minutes, and the supernatant was collected. A dialysis bag with a molecular weight cut-off of 30000 was used to remove byproducts and solvents (dialysis for 3 days, and water change for 3 minutes every day). times, use 2L distilled water each time), after the dialysis is over, take out all the dialysate and vacuum freeze-dry, take an appropriate amount of Mn 3 o 4 -PEI powder is used for X-ray diffraction detection and FTIR testing. XRD results showed that Mn 3 o 4 -The peak position of the PEI nanoparticles is consistent with th...

Embodiment 2

[0085] Get the Mn prepared by embodiment 1 respectively 3 o 4 -PEI-Ac-FI-mPEG-(PEG-FA) nanoparticles and the Mn prepared in Comparative Example 1 3 o 4 -PEI-Ac-FI-mPEG nanoparticle 2mg is dissolved in ultrapure water, obtains nanoparticle suspension, is ultrasonically uniform, and measures the ultraviolet absorption spectrum (see Figure 4 ). The results of UV-Vis spectroscopy test showed that Mn 3 o 4 -PEI-Ac-FI-mPEG-(PEG-FA) and Mn 3 o 4 -PEI-Ac-FI-mPEG has an obvious UV absorption peak at 510nm, which shows that FI is successfully modified to Mn 3 o 4 - PEI nanoparticle surface.

[0086] Take by weighing two kinds of materials that embodiment 1 prepares: Mn 3 o 4 - PEI, Mn 3 o 4 -PEI-Ac-FI-mPEG-(PEG-FA) and the control group material Mn that comparative example 1 obtains 3 o 4 -PEI-Ac-FI-mPEG 2-4mg carries out thermogravimetric analysis (such as Figure 5 shown). TGA test results showed that Mn 3 o 4 -The weight loss of PEI nanoparticles is 54.9% ( Figu...

Embodiment 3

[0091] In order to ensure that the nanoparticles prepared by the present invention can be safely used for in vivo bioimaging diagnosis, the prepared Mn 3 o4 -PEI-Ac-FI-mPEG-(PEG-FA) nanoparticles and control material Mn 3 o 4 - Blood compatibility of PEI-Ac-FI-mPEG. Calculate and weigh out Mn according to the manganese concentration calculation of two kinds of materials measured in embodiment 2 3 o 4 -PEI-Ac-FI-mPEG-(PEG-FA) nanoparticles (embodiment 1) and contrast material Mn 3 o 4 -Two kinds of nanoparticles with 1 mg of manganese total amount in PEI-Ac-FI-mPEG (comparative example 1), were respectively dispersed in PBS to prepare a concentration of 1 mg / mL as mother liquor, and then prepared successively with PBS to have a concentration of 5 μg / mL mL, 10 μg / mL, 25 μg / mL, 50 μg / mL, and 100 μg / mL of nanoparticle suspensions. Take an appropriate amount of human fresh blood, first centrifuge (2000rpm, 5 minutes) to remove the supernatant, then wash the red blood cells 5 ...

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Abstract

The invention relates to a method for preparing a multifunctional manganous manganic oxide nano-particle nuclear magnetic resonance contrast agent mediated by polyethyleneimine. The method comprises the following steps: preparing PEI modified Mn3O4 nano-particles by using a solvothermal method, and then separating and purifying the nano-particles; then, marking tracer molecule fluorescein isothiocyanate FI on the nano-particles; modifying polyethylene glycol PEG molecules on the amino of PEI; and finally, modifying targeted reagent folic acid FA molecules on the PEI through PEG modification and performing complete acetylation treatment to obtain the contrast agent. The contrast agent prepared in the invention can trace the phagocytosis condition of the cancer cells to nanoparticles in a cellular level, has a significant targeting function on a high-expression cancer cell strain of an FA receptor and can be used for achieving early diagnosis of cancer, meanwhile, since the preparation method of the contrast agent is simple and easy and the raw materials are cheap and easy to obtain, the contrast agent can be produced in large batches.

Description

technical field [0001] The invention belongs to the field of preparation of nuclear magnetic resonance contrast agents, in particular to a preparation method of polyethyleneimine-mediated multifunctional trimanganese tetraoxide nanoparticle nuclear magnetic resonance contrast agents. Background technique [0002] Cancer, also known as malignant tumor in medical terms, has directly or indirectly affected the lives of many people and has become the number one killer threatening human health. Therefore, early diagnosis and treatment become the key to cure cancer. In the early diagnosis of tumors, traditional imaging techniques can only understand tumor volume and anatomical location, while molecular imaging techniques can obtain more detection parameters, such as the evaluation of tumor growth kinetics, the detection of molecular abnormalities before malignant transformation, tumor cell Markers, etc., and in vivo molecular imaging can realize the study of pathogenesis without ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K49/12A61K49/18
Inventor 史向阳罗宇于智博
Owner DONGHUA UNIV
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