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Manganese oxide nanoparticle contrast agent for specifically targeting brain glioma

A brain glioma, manganese oxide technology, applied in the preparations, emulsion delivery, pharmaceutical formulations and other directions for in vivo experiments, can solve the problems of low relaxation rate, inability to clearly define the tumor boundary, etc., and achieve a good biological phase. Capacitive, obvious contrast-enhancing effects

Inactive Publication Date: 2014-01-08
CAPITAL UNIVERSITY OF MEDICAL SCIENCES
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Compared with gadolinium-based contrast agents, the reported manganese oxide nanoparticle contrast agents have lower relaxation rates (0.1-2mM -1 the s -1 ), and has no specific targeting for glioma cells, and cannot clearly define the tumor boundary

Method used

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  • Manganese oxide nanoparticle contrast agent for specifically targeting brain glioma
  • Manganese oxide nanoparticle contrast agent for specifically targeting brain glioma
  • Manganese oxide nanoparticle contrast agent for specifically targeting brain glioma

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0037] 1) Preparation of manganese oxide nanoparticles coated with oleic acid:

[0038] Manganese oxide nanoparticles coated with oleic acid were synthesized by pyrolysis: manganese chloride tetrahydrate (3.96g, 20mmol), sodium oleate (12.17g, 40mmol) were dispersed in ethanol (40ml), water (30ml), n-hexane (70ml) of the mixed solution was stirred at 70°C for 4 hours, the organic phase was taken and washed with a small amount of water, and the solvent was removed to obtain a manganese oleate precursor. The prepared manganese oleate precursor (2.468g, 4mmol) was dissolved in 1-octadecene (50ml), and stirred under vacuum at 100°C for 30-60min. Under the protection of nitrogen, the temperature was raised to 300°C and refluxed for 15 minutes, then cooled to room temperature. After adding absolute ethanol and centrifuging, the resulting black precipitate was dispersed in n-hexane and washed with a small amount of absolute ethanol to obtain manganese oxide nanoparticles coated with...

Embodiment 2

[0049] Determination of relaxation rate:

[0050] Manganese oxide nanoparticles in Example 1 are prepared into a series of concentration suspensions, and the RARE-T is used on the 7T nuclear magnetic resonance instrument 1 +T 2 -map sequences to determine relaxation rates. The parameters are set as follows: TR=800ms, TE=11ms, 33ms, 55ms, 77ms, 99ms, matrix size=256×256, FOV=4.0×4.0cm 2 , flip angle(FA)=180° and slice thickness=1mm, T 1 weighted imaging scan, the resulting transverse relaxation time (T 1 ) is linearly fitted to the concentration, and the slope of the obtained line is the relaxation rate. Its fitting curve see Figure 5 . From Figure 5 It can be seen that the relaxation time decreases significantly with the increase of manganese concentration. Obtain manganese oxide nanoparticles r in embodiment 1 by linear fitting 1 Relaxation rate 4.8mM -1 the s -1

Embodiment 3

[0052] Cytotoxicity:

[0053] 1) Cell culture: C6 glioma cells were cultured in DMEM medium (containing 10% fetal bovine serum, 100U / ml penicillin, 100U / ml streptomycin) at 37°C with 5% CO 2 for 24 hours in a humidified incubator.

[0054] 2) Cytotoxicity: C6 glioma cells were treated with 1×10 5 The cell density was seeded in a 96-well plate and incubated for 24 hours. The manganese oxide nanoparticles in Example 1 were formulated into solutions with a manganese concentration of 0, 6.125, 12.5 and 25 μg / mL, respectively, and added to 96-well plates, and after co-incubating for 24 hours and 48 hours, discard the solutions containing Wash the medium of nanoparticles twice with PBS, add MTT (100μl, 0.5mg / ml), incubate for another 4 hours, discard MTT, add 150μl DMSO, shake for 5 minutes in the dark, and use a microplate reader to measure at 570nm wavelength OD value of each well. The calculated cell viability at different manganese oxide nanoparticles concentrations is shown...

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Abstract

The invention discloses a manganese oxide nanoparticle contrast agent for specifically targeting brain glioma. The manganese oxide nanoparticle contrast agent is prepared by the following steps: dispersing an inorganic manganese compound and sodium oleate into a mixed liquor of ethanol, water and normal hexane, and reacting at 50-70 DEG C to prepare precursor manganese oleate; dissolving the manganese oleate precursor into 1-octadecene, and stirring at 80-100 DEG C under protection of nitrogen; heating to 280-320 DEG C under protection of nitrogen, and refluxing to obtain oleic acid-encapsulated manganese oxide nanoparticles; dispersing the oleic acid-encapsulated manganese oxide nanoparticles into methylbenzene; adding a little of acetic acid, carrying out ultrasonic treatment, and adding a silylating reagent to react, so as to obtain silylanized manganese oxide nanoparticles; dispersing the manganese oxide nanoparticles into deionized water, and bonding specifically targeted molecules of the brain glioma, so as to obtain the manganese oxide nanoparticles for specifically targeting the brain glioma. The manganese oxide nanoparticles disclosed by the invention can be used as a novel nuclear magnetic resonance imaging (MRI) contrast agent for early diagnosis and boundary definition of the brain glioma.

Description

technical field [0001] The invention relates to a water-dispersed manganese oxide nanoparticle specifically targeting brain gliomas. [0002] The present invention also relates to a preparation method of the above-mentioned manganese oxide nanoparticles. [0003] The present invention also relates to the aforementioned manganese oxide nanoparticles as a new type of MRI T 1 Application of contrast agent in early diagnosis and border definition of glioma. Background technique [0004] Glioma is the most common primary intracranial malignant tumor. Difficulties in early diagnosis and boundary definition of glioma are the main reasons for the high mortality rate of glioma patients. Contrast-enhanced magnetic resonance imaging (MRI) can more clearly distinguish pathological tissue from normal tissue. If negative (T 2 ) contrast agent to darken the contrast area, thereby improving the contrast between tumor tissue and normal tissue. However, haemorrhage, calcification, and s...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K49/18A61K49/10
Inventor 顾微肖宁陈宁李帅郑婷婷于春江叶玲
Owner CAPITAL UNIVERSITY OF MEDICAL SCIENCES
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