Contrast agent having two functions of up-conversion luminescence and magnetic resonance imaging, and method for preparing same

Abstract

The invention relates to a contrast agent having two functions of up-conversion luminescence and magnetic resonance imaging, and a method for preparing the same. The contrast agent is obtained by modifying a gadolinium chelating agent on the surfaces of carbon nanospheres through taking up-conversion luminescent material carbon nanospheres as cores and using a coupling agent, wherein the mol ratio of the carbon nanospheres to the coupling agent to the gadolinium chelating agent is 1: 1: 1 to10: 1: 1. The dual-function contrast agent is small in grain size, high in crystallinity, even in dispersion, stable in performance, and strong in both fluorescence and magnetic resonance signal. The product obtained is capable of meeting the requirements of clinical application.

Description

technical field

[0001] The invention relates to a carbon nanosphere contrast agent and a preparation method thereof, in particular to a contrast agent with dual functions of up-conversion luminescence and magnetic resonance imaging and a preparation method thereof. Background technique

[0002] In the field of biomedicine, staining, labeling and detection of cells and biomolecules has always been an important part of biomedical analysis. In recent years, with the rapid development of nanotechnology, the application of nanomaterials in biomarkers has attracted widespread attention. The use of nanoparticles as new markers for biomarkers can not only effectively overcome the defects of traditional organic dye markers, but also broaden the development direction for biomarker technology. At present, the fluorescent nano-labeling materials used in the field of biological analysis mainly include quantum dots, rare earth-doped luminescent nanoparticles (such as up-conversion lumine...

Examples

Embodiment 1

[0032] Embodiment one: the specific method is:

[0033] 1. Mix 1 g (3 × 10 -3 mol) soluble starch was dissolved in 20 mL of deionized solution to make a solution with a concentration of 50 g / L, and stirred thoroughly. Transfer the reaction solution into a high-pressure reactor with a 25 ml polytetrafluoroethylene liner, and react at 160??C for 12 hours. After the reaction, the reactor is naturally cooled to about 60??C, and the and deionized water for several times, centrifuged and dried in vacuum to obtain carbon nanospheres.

[0034] 2. Add 3 × 10 to 50 mL DMSO -3 mol DTPA, after completely dissolved, add 3 × 10 -3 mol of NHS and EDC, stirred at room temperature for 24 hours. will be 3 x 10 -3 mol carbon nanospheres are dispersed in the solution, and 3 × 10 -3mol of NHS and EDC, stirred at room temperature for 24 hours. The product was filtered, washed several times with absolute ethanol and deionized water successively, and vacuum-dried to obtain DTPA-modified ca...

Embodiment 2

[0038] Embodiment two: concrete steps are:

[0039] 1. Combine 1.1 g (6 × 10 -3 mol) of glucose was dissolved in 20 mL of deionized solution to make a solution with a concentration of 55 g / L, and stirred thoroughly. Transfer the reaction solution into a high-pressure reactor with a 25 ml polytetrafluoroethylene liner. Under the condition of 200?? C, the reaction time is 6 hours. After the reaction, the reactor is naturally cooled to about 60?? and deionized water for several times, centrifuged and dried in vacuum to obtain carbon nanospheres.

[0040] 2. Add 6 × 10 to 50 mL DMSO -3 mol DOTA, after completely dissolved, add 6 × 10 -3 mol of NHS and EDC, stirred at room temperature for 24 hours. will be 3 x 10 -2 mol carbon nanospheres are dispersed in the solution, add 6 × 10 -3 mol of NHS and EDC, stirred at room temperature for 12 hours. The product was filtered, washed several times with absolute ethanol and deionized water successively, and vacuum-dried to obtai...

Embodiment 3

[0044] Embodiment three: concrete steps are:

[0045] 1. Mix 2.05g (6 × 10 -3 mol) of sucrose was dissolved in 20 mL of deionized solution to make a solution with a concentration of 102.5 g / L and stirred thoroughly. Transfer the reaction solution to a high-pressure reactor with a 25 ml polytetrafluoroethylene liner. Under the condition of 100?? C, the reaction time is 20 hours. After the reaction, the reactor is naturally cooled to about 60?? and deionized water for several times, centrifuged and dried in vacuum to obtain carbon nanospheres.

[0046] 2. Add 6 × 10 to 50 mL DMSO -3 mol DTPA-BMA, after complete dissolution, add 6 × 10 -3 mol of NHS and EDC, stirred at room temperature for 24 hours. will be 2 x 10 -2 mol carbon nanospheres are dispersed in the solution, add 6 × 10 -3 mol of NHS and EDC, stirred at room temperature for 6 hours. The product was filtered, washed several times with absolute ethanol and deionized water successively, and vacuum-dried to obt...

technical field

[0001] The invention relates to a carbon nanosphere contrast agent and a preparation method thereof, in particular to a contrast agent with dual functions of up-conversion luminescence and magnetic resonance imaging and a preparation method thereof. Background technique

[0002] In the field of biomedicine, staining, labeling and detection of cells and biomolecules has always been an important part of biomedical analysis. In recent years, with the rapid development of nanotechnology, the application of nanomaterials in biomarkers has attracted widespread attention. The use of nanoparticles as new markers for biomarkers can not only effectively overcome the defects of traditional organic dye markers, but also broaden the development direction for biomarker technology. At present, the fluorescent nano-labeling materials used in the field of biological analysis mainly include quantum dots, rare earth-doped luminescent nanoparticles (such as up-conversion lumine...

Examples

Embodiment 1

[0032] Embodiment one: the specific method is:

[0033] 1. Mix 1 g (3 × 10 -3 mol) soluble starch was dissolved in 20 mL of deionized solution to make a solution with a concentration of 50 g / L, and stirred thoroughly. Transfer the reaction solution into a high-pressure reactor with a 25 ml polytetrafluoroethylene liner, and react at 160??C for 12 hours. After the reaction, the reactor is naturally cooled to about 60??C, and the and deionized water for several times, centrifuged and dried in vacuum to obtain carbon nanospheres.

[0034] 2. Add 3 × 10 to 50 mL DMSO -3 mol DTPA, after completely dissolved, add 3 × 10 -3 mol of NHS and EDC, stirred at room temperature for 24 hours. will be 3 x 10 -3 mol carbon nanospheres are dispersed in the solution, and 3 × 10 -3mol of NHS and EDC, stirred at room temperature for 24 hours. The product was filtered, washed several times with absolute ethanol and deionized water successively, and vacuum-dried to obtain DTPA-modified ca...

Embodiment 2

[0038] Embodiment two: concrete steps are:

[0039] 1. Combine 1.1 g (6 × 10 -3 mol) of glucose was dissolved in 20 mL of deionized solution to make a solution with a concentration of 55 g / L, and stirred thoroughly. Transfer the reaction solution into a high-pressure reactor with a 25 ml polytetrafluoroethylene liner. Under the condition of 200?? C, the reaction time is 6 hours. After the reaction, the reactor is naturally cooled to about 60?? and deionized water for several times, centrifuged and dried in vacuum to obtain carbon nanospheres.

[0040] 2. Add 6 × 10 to 50 mL DMSO -3 mol DOTA, after completely dissolved, add 6 × 10 -3 mol of NHS and EDC, stirred at room temperature for 24 hours. will be 3 x 10 -2 mol carbon nanospheres are dispersed in the solution, add 6 × 10 -3 mol of NHS and EDC, stirred at room temperature for 12 hours. The product was filtered, washed several times with absolute ethanol and deionized water successively, and vacuum-dried to obtai...

Embodiment 3

[0044] Embodiment three: concrete steps are:

[0045] 1. Mix 2.05g (6 × 10 -3 mol) of sucrose was dissolved in 20 mL of deionized solution to make a solution with a concentration of 102.5 g / L and stirred thoroughly. Transfer the reaction solution to a high-pressure reactor with a 25 ml polytetrafluoroethylene liner. Under the condition of 100?? C, the reaction time is 20 hours. After the reaction, the reactor is naturally cooled to about 60?? and deionized water for several times, centrifuged and dried in vacuum to obtain carbon nanospheres.

[0046] 2. Add 6 × 10 to 50 mL DMSO -3 mol DTPA-BMA, after complete dissolution, add 6 × 10 -3 mol of NHS and EDC, stirred at room temperature for 24 hours. will be 2 x 10 -2 mol carbon nanospheres are dispersed in the solution, add 6 × 10 -3 mol of NHS and EDC, stirred at room temperature for 6 hours. The product was filtered, washed several times with absolute ethanol and deionized water successively, and vacuum-dried to obt...

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