Nanobubbles for enhanced ultrasound imaging of tumors

Int J Nanomedicine. 2012;7:895-904. doi: 10.2147/IJN.S28830. Epub 2012 Feb 22.


The fabrication and initial applications of nanobubbles (NBs) have shown promising results in recent years. A small particle size is a basic requirement for ultrasound contrast-enhanced agents that penetrate tumor blood vessel pores to allow for targeted imaging and therapy. However, the nanoscale size of the particles used has the disadvantage of weakening the imaging ability of clinical diagnostic ultrasound. In this work, we fabricated a lipid NBs contrast-enhanced ultrasound agent and evaluated its passive targeting ability in vivo. The results showed that the NBs were small (436.8 ± 5.7 nm), and in vitro ultrasound imaging suggested that the ultrasonic imaging ability is comparable to that of microbubbles (MBs). In vivo experiments confirmed the ability of NBs to passively target tumor tissues. The NBs remained in the tumor area for a longer period because they exhibited enhanced permeability and retention. Direct evidence was obtained by direct observation of red fluorescence-dyed NBs in tumor tissue using confocal laser scanning microscopy. We have demonstrated the ability to fabricate NBs that can be used for the in vivo contrast-enhanced imaging of tumor tissue and that have potential for drug/gene delivery.

Keywords: contrast agent; phospholipids; tumor-targeted; ultrasound.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analysis of Variance
  • Animals
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Contrast Media / chemistry*
  • Contrast Media / pharmacokinetics
  • Fluorescent Dyes / chemistry
  • Fluorescent Dyes / pharmacokinetics
  • Hemolysis / drug effects
  • Mice
  • Microbubbles*
  • Microscopy, Confocal
  • Nanostructures / chemistry*
  • Nanotechnology
  • Neoplasms / diagnostic imaging*
  • Particle Size
  • Phospholipids / chemistry
  • Phospholipids / pharmacokinetics
  • Rats
  • Rats, Sprague-Dawley
  • Tissue Distribution
  • Ultrasonography / instrumentation*


  • Contrast Media
  • Fluorescent Dyes
  • Phospholipids