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Novel three-mode contrast agent and preparation method thereof

A contrast agent and three-mode technology, applied in MRI/MRI contrast agents, pharmaceutical formulations, echo/ultrasound imaging agents, etc., can solve the problems of non-enhanced MR imaging, ultrasound and CT imaging, etc., to achieve clinical Great transformation potential, improved MR imaging, pollution-free results

Inactive Publication Date: 2015-12-23
SHANGHAI TENTH PEOPLES HOSPITAL
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

We have previously prepared amino-functionalized hollow mesoporous silica with adjustable size, and further reacted with chloroauric acid to produce a heterogeneous rattle structure with gold as the core, and the core size can be adjusted (CN102530969A), but the research report Ultrasound and CT imaging studies were not performed, and there is no capability to enhance MR imaging

Method used

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  • Novel three-mode contrast agent and preparation method thereof
  • Novel three-mode contrast agent and preparation method thereof
  • Novel three-mode contrast agent and preparation method thereof

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preparation example Construction

[0045] Regarding the preparation of Au@HMSN / Au, please also refer to prior art literature (eg CN102530969A). In one example, HMSN is dispersed in a chloroauric acid solution with a concentration of 0.0125-0.05M at a mass ratio of chloroauric acid to hollow mesoporous silica nanoparticles of 1:(2-4), and hydrothermal Reaction, the hydrothermal reaction temperature can be 75-85°C, and the hydrothermal reaction time can be 40-120 minutes, and gold nanoparticles with a core size of 40-60nm are prepared to form Au@HMSN / Au. Among them, the concentration of chloroauric acid is preferably 0.05M, the mass ratio of chloroauric acid to HMSN is 1:2.7, the reaction temperature is 80° C., and the time is 2 hours to prepare gold nanoparticles with a core size of 50 nm.

[0046] After the reaction of HMSN with chloroauric acid to prepare Au@HMSN / Au, there are still residual amino groups that can be further reacted with potassium permanganate in step 3) to prepare MnO nanoparticles and realize...

Embodiment 1

[0066] Preparation of amino-functionalized hollow mesoporous silica nanoparticles: mix 71.6ml of absolute ethanol, 10ml of deionized water and 3.14ml of ammonia water, stir at 30°C for 30min; quickly add 6ml of ethyl orthosilicate, magnetically stir 45min; After mixing 5ml tetraethyl orthosilicate and 2ml 3-aminopropyltrimethoxysilane evenly, quickly add the above solution, stir magnetically for 80min, and obtain a highly dispersed homogeneous solid core / shell mesoporous oxidation product after centrifugation Silicon nanospheres. The centrifuged product is dispersed with 0.6mol / L Na 2 CO 3 in solution. The dispersed sol was stirred at 80°C for 60 min. After centrifugation, the product was washed three times with deionized water, and freeze-dried to obtain HMSN.

Embodiment 2

[0068] Immerse 100 mg of the amino-functionalized hollow mesoporous SiO2 nanoparticle material prepared in Example 1 in 15 ml of 0.05M HAuCl4 solution, ultrasonically disperse it for 30 minutes, and then place it in a water bath at 80°C for 2 hours to form a heterogeneous material with gold as the core. The rattle structure, the surface is loaded with small gold nanoparticles at the same time, to obtain Au@HMSN / Au, the product is centrifuged, washed 3 times with water, and freeze-dried.

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Abstract

The invention relates to a novel three-mode contrast agent and a preparation method thereof. The contrast agent consists of a hollow mesoporous silicon oxide shell, first gold nanoparticles which are arranged in a hollow cavity of the hollow mesoporous silicon oxide shell and are used as a core, and second gold nanoparticles and MnO nanoparticles which are uniformly dispersed in a shell layer of the hollow mesoporous silicon oxide shell. The three-mode contrast agent provided by the invention is prepared by designing an assembly structure, wherein a heterogeneous rattle structure constituted by the hollow mesoporous silicon oxide nanoparticles and the large core gold nanoparticles can arouse double scattering in a single particle; the Au nanoparticles and the MnO nanoparticles uniformly dispersed in the shell layer can enhance non-linear scattering, and can further enhance ultrasound imaging; in addition, by virtue of the MnO nanoparticles which are uniformly dispersed, the probability and the area of getting into contact with water molecules are improved, so that MR imaging is significantly enhanced; and by virtue of a nuclear-satellite structure formed by the gold nanoparticles, an X-ray absorption efficiency is significantly enhanced and a CT contrast effect is improved.

Description

technical field [0001] The invention belongs to the field of nano-biomedicine, and in particular relates to a three-mode contrast agent which integrates enhanced ultrasound, nuclear magnetic and CT imaging effects, a preparation method thereof and positive charge surface modification. Background technique [0002] Cancer is a major disease that seriously threatens human health. Early diagnosis and early intervention are the only chances for cancer patients to obtain long-term survival and improve prognosis, especially early diagnosis has become the direction and focus of current research and development. Molecular imaging is a non-invasive imaging mode that has rapidly emerged in the field of biomedicine in recent years. It refers to the use of molecular imaging agents to target specific receptors or ligands in vivo, and to detect molecular levels in vivo in vitro. Learn to change. However, among the current numerous molecular imaging methods, such as nuclear magnetic reson...

Claims

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Application Information

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IPC IPC(8): A61K49/22A61K49/00A61K49/06A61K49/12
Inventor 徐辉雄张坤贺亚萍
Owner SHANGHAI TENTH PEOPLES HOSPITAL