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Paramagnetic metal complex functionalized fluorogold nano-cluster magnetic resonance and fluorescence imaging contrast agent

A technology of fluorescent gold nanometers and paramagnetic metals, which can be used in pharmaceutical formulations, animal/human proteins, preparations for in vivo experiments, etc., and can solve problems such as poor selectivity of tissues and organs, low relaxation efficiency of contrast agents, and rapid metabolism in vivo , to achieve improved relaxation efficiency, good fluorescence imaging effect, and increased molecular volume

Inactive Publication Date: 2012-03-07
CHANGCHUN UNIV OF TECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0004] The purpose of the present invention is to solve the problems of low relaxation efficiency, high toxicity, poor tissue and organ selectivity and fast metabolism in the body of contrast agents in the prior art, and provide fluorescent gold nanoclusters functionalized with paramagnetic metal complexes for magnetic resonance and Fluorescent Imaging Contrast Agents

Method used

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  • Paramagnetic metal complex functionalized fluorogold nano-cluster magnetic resonance and fluorescence imaging contrast agent
  • Paramagnetic metal complex functionalized fluorogold nano-cluster magnetic resonance and fluorescence imaging contrast agent
  • Paramagnetic metal complex functionalized fluorogold nano-cluster magnetic resonance and fluorescence imaging contrast agent

Examples

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Embodiment 1

[0038] Fluorescent Gold Nanoclusters Au-BSA-FA-(Gd-DTPA) Functionalized by Gadolinium Diethylenetriamine Pentaacetate Complex 12 Preparation of contrast agents for magnetic resonance and fluorescence imaging:

[0039] Step 1: Mix 5mL1ommol·L -1 HAuCl 4 Add the solution to 5mL 50mg·mL -1 BSA solution, mix well, add 0.5mL 1mol L after 3min -1 NaOH solution to obtain a mixed solution, the mixed solution was placed in a constant temperature water bath at 37°C for 12 hours with magnetic stirring, and the mixed solution was freeze-dried to prepare the gold nanocluster Au-BSA;

[0040] Step 2: Take 5 mg of folic acid, dissolve it in 5 ml of DMSO, then add 10.8 mg of EDC, and stir at 25°C in the dark for 1 hour to obtain a DMSO solution of folic acid activated ester. Take 2 ml of the gold nanocluster Au-BSA described in step 1, Add 1ml of 0.05mol·L -1 , PBS buffer solution with pH=9, after mixing, add it into the DMSO solution of folic acid activated ester, and stir at 25°C for 1...

Embodiment 2

[0046] Fluorescent gold nanoclusters Au-BSA-FA-(Eu-DTPA) functionalized with europium complexes of diethylenetriaminepentaacetate 11 Preparation of contrast agents for magnetic resonance and fluorescence imaging:

[0047] Step one to step three are the same as step one to step three in embodiment 1;

[0048] Step 4: Take 8ml of the Au-BSA-FA solution described in step 2, add 1ml of phosphate buffer solution, then add 14mg of DTPA bis-acid anhydride described in step 3 to obtain a mixed solution, and use 5mol L -1 Control the pH value of the above-mentioned mixed solution between 5 and 7 with NaOH solution, stir at 25°C for 2 hours, and freeze-dry the above-mentioned mixed solution to prepare the DTPA-modified fluorescent gold nanocluster macromolecule ligand;

[0049] Step 5: Add 18 mg of EuCl to the DTPA-modified fluorescent gold nanocluster macromolecule ligand described in step 4 3 ·6H 2 O, continue to stir for 2h to obtain a mixed solution, which is dialyzed with twice ...

Embodiment 3

[0052] Fluorescent gold nanoclusters Au-BSA-FA-(Fe-DTPA) functionalized with diethylenetriaminepentaacetic acid complex 13 Preparation of contrast agents for magnetic resonance and fluorescence imaging:

[0053] Step one to step three are the same as step one to step three in embodiment 1;

[0054] Step 4: Take 8ml of the Au-BSA-FA solution described in step 2, add 1ml of phosphate buffer solution, then add 56mg of DTPA bis-anhydride described in step 3 to obtain a mixed solution, and use 5mol L -1 Control the pH value of the above-mentioned mixed solution between 5 and 7 with NaOH solution, stir at 25°C for 2 hours, and freeze-dry the above-mentioned mixed solution to prepare the DTPA-modified fluorescent gold nanocluster macromolecular ligand;

[0055] Step 5: Add 42 mg of FeCl to the DTPA-modified fluorescent gold nanocluster macromolecule ligand described in step 4 3 ·6H 2 O, continue to stir for 2h to obtain a mixed solution, which is dialyzed with twice distilled wate...

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Abstract

The invention provides a paramagnetic metal complex functionalized fluorogold nano-cluster magnetic resonance and fluorescence imaging contrast agent. The invention relates to the field of magnetic resonance imaging and fluorescence imaging contrast agents. With the contrast agent provided by the invention, problems of existing contrast agents of low relaxation efficiency, high toxicity, low tissue organ selectivity and fast in-vivo metabolism can be solved. According to the invention, ethylenediaminetetraacetic acid (EDTA) or diethylene triaminepentaacetic acid (DTPA) are connected to folic-acid-modified bovine serum albumin fluorogold nano-clusters through amide bonds; and EDTA or DTPA is respectively coordinated with paramagnetic metal ions, such that the complex is obtained. With the contrast agent provided by the invention, the relaxation efficiency can reach 23.7mM<-1>*s<-1>. The contrast agent has an advantage of low toxicity. According to the invention, high spatial resolution of magnetic resonance imaging and high sensitivity of fluorescence imaging are combined. Therefore, the contrast agent provided by the invention can be used in magnetic resonance imaging and fluorescence imaging.

Description

technical field [0001] The invention relates to magnetic resonance imaging and fluorescence imaging contrast agents, more specifically, to fluorescent gold nanocluster magnetic resonance and fluorescence imaging contrast agents functionalized with paramagnetic metal complexes. Background technique [0002] Magnetic resonance imaging (MRI) contrast agent is a kind of imaging enhancement contrast agent that can shorten imaging time, improve imaging contrast and clarity, it can change the relaxation rate of water protons in local tissues in the body, and improve Imaging contrast, thus revealing the functional status of internal organs. The most widely used contrast agent in clinical practice is (NMG) [Gd(DTPA)·H] approved by the German Health Bureau in 1988. 2 O] (trade name Magnevist). In addition, eight kinds of gadolinium complexes and one manganese complex have been approved for clinical application, which can be divided into ionic contrast agents such as Gd-DOTA (Journal...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K49/00A61K49/14C07K14/765
Inventor 孙国英周蕾赵振波
Owner CHANGCHUN UNIV OF TECH
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