Medical Contrast Agent Made of Microbubbles Containing Fluorescent Gold Nanoclusters

Abstract

A medical contrast agent made of microbubbles containing Au nanoclusters is provided. The shell of the microbubbles contains fluorescent Au nanocluster-albumin complex, and the core contains air or fluorocarbons. The method for preparing the microbubbles is also disclosed.

1 . A medical contrast agent made of microbubbles containing Au nanoclusters, each microbubble comprising:
 a shell comprising a plurality of Au nanocluster-albumin complex, wherein the structure of the each complex comprises fluorescent Au nanocluster surrounded by a layer of a first albumin; and   a core filled with air or fluorocarbons in the shell.   
     
     
         2 . The medical contrast agent of  claim 1 , wherein the first albumin is a serum albumin, an ovalbumin, or a storage albumin. 
     
     
         3 . The medical contrast agent of  claim 1 , wherein the shell further comprising a second albumin. 
     
     
         4 . The medical contrast agent of  claim 3 , wherein the second albumin is a serum albumin, an ovalbumin, or a storage albumin. 
     
     
         5 . The medical contrast agent of  claim 1 , wherein the structure of the complex further comprises a layer of a protecting ligand between the fluorescent Au nanocluster and the layer of the first albumin. 
     
     
         6 . The medical contrast agent of  claim 5 , wherein the protecting ligand is a non-albumin molecule, which is dihydrolipoic acid, glutathione, tiopronin, meso-2,3-dimercaptosuccunic acid, phenylethylthiolate, dodecanethiol, or mercaptoundecanol. 
     
     
         7 . The medical contrast agent of  claim 5 , wherein the shell further comprising a third albumin. 
     
     
         8 . The medical contrast agent of  claim 7 , wherein the third albumin is a serum albumin, an ovalbumin, or a storage albumin. 
     
     
         9 . The medical contrast agent of  claim 1 , wherein the diameter of the microbubbles is about 0.5-6 μm. 
     
     
         10 . A method of preparing microbubbles containing Au nanoclusters, comprising:
 mixing a Au 3+  solution and a first albumin solution to form a mixing solution;   reducing Au 3+  by adding a base into the mixing solution to form a fluorescent Au nanocluster-albumin complex, wherein the Au nanocluster is protected by a layer of the first albumin;   dispersing the Au nanocluster-albumin complex in water or phosphate buffered saline to form a dispersed solution; and   sonicating the dispersed solution at a ultrasound intensity of about 11-24 watts for about 1-3 minutes to form microbubbles.   
     
     
         11 . The method of  claim 10 , wherein the first albumin is a serum albumin, an ovalbumin, or a storage albumin. 
     
     
         12 . The method of  claim 11 , further comprising adding a second albumin in the dispersed solution. 
     
     
         13 . The method of  claim 10 , wherein the base is NaOH or KOH. 
     
     
         14 . A method of preparing microbubbles containing Au nanoclusters, comprising:
 synthesizing fluorescent Au nanocluster-ligand complex having a structure of a Au nanocluster protected by a layer of the ligand;   mixing a solution of the Au nanocluster-ligand complex and a solution of a albumin to form Au-albumin complexes, in which a layer of albumin surrounds each of the Au-ligand complexes;   dispersing the Au nanocluster-albumin complex in water or phosphate buffered saline to form a dispersed solution; and   sonicating the dispersed solution at a ultrasound intensity of about 11-24 watts for about 1-3 minutes to form microbubbles.   
     
     
         15 . The method of  claim 14 , wherein the ligand is dihydrolipoic acid, glutathione, tiopronin, meso-2,3-dimercaptosuccunic acid, phenylethylthiolate, dodecanethiol, or mercaptoundecanol. 
     
     
         16 . The method of  claim 14 , wherein the albumin is a serum albumin, an ovalbumin, or a storage albumin. 
     
     
         17 . The method of  claim 14 , further comprising adding a second albumin in the dispersed solution. 
     
     
         18 . The method of  claim 14 , wherein the step of synthesizing Au nanocluster-ligand complex comprises:
 mixing a Au 3+  solution and a ligand solution to form a mixing solution; to and   reducing Au 3+  by adding a reductant into the mixing solution to form a plurality of Au nanocluster-ligand complexes.   
     
     
         19 . The method of  claim 14 , wherein the step of synthesizing Au is nanocluster-ligand complex comprises:
 reducing Au 3+  in a solution by adding a reductant to obtain Au nanoparticles suspending in the solution;   etching the Au nanoparticles by adding further Au 3+  to the solution to obtain fluorescent Au nanocluters; and   adding a protecting ligand into the solution to obtain the Au nanocluster-ligand complex.   
     
     
         20 . The method of  claim 19 , wherein the reductant comprises tetrabutylammonium borohydride (TBAB).