Core-shell type tri-modal nano contrast agent as well as preparation method and application thereof

A nano-contrast agent and three-modal technology, applied in X-ray contrast agent preparation, pharmaceutical formulations, preparations for in vivo tests, etc., can solve the problems of reduced efficiency and sensitivity, achieve simple preparation methods, change absorption, absorb high rate effect

Inactive Publication Date: 2013-04-03
SHENZHEN INST OF ADVANCED TECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] In addition, nanoparticles with a diameter greater than 20 nm are easily phagocytosed by the reticuloendothelial system (RES), resulting in reduced efficiency and sensitivity.

Method used

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  • Core-shell type tri-modal nano contrast agent as well as preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0037] a. Preparation of gold nanoclusters:

[0038] Warm bath 10mmol / L chloroauric acid solution and 50mg / mL HSA solution at 37°C, keep the temperature of the above two solutions to 37°C, add 0.5mL chloroauric acid solution to 0.5mL HSA solution, mix well, and then add 0.05mL of 1mol / L NaOH solution, adjust the pH value to be strongly alkaline (pH10.0-14.0), and place the resulting mixture in a shaker at 37°C for 12h to form a metal nanocluster solution.

[0039] b. Chelating agent is covalently bound to metal nanoclusters:

[0040] Take 4ml of the above metal nanocluster solution, add 0.2mL of PBS solution (2mol / L, pH=9), mix, add 28mg of DTPACA powder to the above mixed solution, titrate with 5mol / L NaOH solution, adjust the pH value to 6.0-8.0 , placed on a shaking table at room temperature for 2 h to obtain a chelating agent-metal nanocluster solution.

[0041] c. Chelating agent-metal nanoclusters coordinate with paramagnetic metal ions:

[0042] Weigh 30mg GdCl 3 .6...

Embodiment 2

[0047] a. Preparation of gold nanoclusters:

[0048] Warm bath 10mmol / L chloroauric acid solution and 50mg / mL HSA solution at 37°C, keep the temperature of the above two solutions to 37°C, add 1mL chloroauric acid solution to 1mL HSA solution, mix well, then add 1mol / mL 0.05 mL of L NaOH solution, adjust the pH value to be strongly alkaline (pH10.0-14.0), and place the resulting mixture in a shaker at 37°C for 24 hours to form a metal nanocluster solution.

[0049] b. Chelating agent is covalently bound to metal nanoclusters:

[0050] Take 5ml of the above metal nanocluster solution, add 0.2mL of PBS solution (4mol / L, pH=9), mix, add 40mg of DTPACA powder to the above mixed solution, titrate with 5mol / L NaOH solution, adjust the pH to 9.0, and Placed on a shaking table for 1 h to obtain a chelating agent-metal nanocluster solution.

[0051] c. Chelating agent-metal nanoclusters coordinate with paramagnetic metal ions:

[0052] Weigh 50mg GdCl 3 .6H 2 O is dissolved in 0.0...

Embodiment 3

[0056] a. Preparation of gold nanoclusters:

[0057] Warm bath 20mmol / L chloroauric acid solution and 100mg / mL HSA solution at 37°C, keep the temperature of the above two solutions to 37°C, add 0.5mL chloroauric acid solution to 0.5mL HSA solution, mix well, and then add 0.1 mL of 1 mol / L NaOH solution, adjust the pH value to be strongly alkaline (pH10.0-14.0), and incubate the resulting mixture on a shaker at 37 °C for 20 h to form a metal nanocluster solution.

[0058] b. Chelating agent is covalently bound to metal nanoclusters:

[0059] Take 4ml of the above metal nanocluster solution, add 0.1mL of PBS solution (3mol / L, pH=9), mix, add 50mg of DTPACA powder to the above mixed solution, titrate with 3mol / L NaOH solution, adjust the pH value to 10.0, and Placed on a shaking table for 3 hours to obtain a chelating agent-metal nanocluster solution.

[0060] c. Chelating agent-metal nanoclusters coordinate with paramagnetic metal ions:

[0061] Weigh 70mg GdCl 3 .6H 2 O is...

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Abstract

The invention discloses a core-shell type tri-modal nano contrast agent, which comprises a metal nano-cluster inner core, wherein the metal nano-cluster inner core comprises metal, human serum albumin and a paramagnetic metal ion coordination compound shell; the human serum albumin is assembled outside the metal to serve as a protecting group; and the paramagnetic metal ion coordination compound shell is used for coating the metal nano-cluster inner core, the shell comprises a chelating agent and paramagnetic metal ions, the chelating agent is connected with the human serum albumin in a covalent manner through an amido bond, and the paramagnetic metal ions are combined on the chelating agent in a coordination manner. The invention further provides a preparation method of the core-shell type tri-modal nano contrast agent.

Description

technical field [0001] The invention relates to multimodal imaging technology, in particular to an MRI / NIR / CT three-modal nano-contrast agent, its preparation method and application. Background technique [0002] Tumor is one of the important diseases that threaten human health. Early diagnosis and treatment of tumor is the key to improve the quality of life and cure rate of patients. At present, molecular imaging technologies applied to tumors include optical imaging technology, CT (computerized tomography) imaging technology, MRI (magnetic resonance imaging) molecular imaging technology, ultrasonic molecular imaging technology, SPECT technology, PET technology and NIR (near infrared fluorescence imaging technology). imaging) technology. However, single molecular imaging technology has its own insurmountable defects, such as fluorescence imaging is difficult to obtain quantitative information in the human body, especially in deep tissues, CT imaging technology lacks specif...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K49/18A61K49/14A61K49/00A61K49/04
Inventor 蔡林涛胡德红盛宗海龚萍高笃阳张鹏飞
Owner SHENZHEN INST OF ADVANCED TECH
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