Ultrasound molecular imaging of breast cancer in MCF-7 orthotopic mice using gold nanoshelled poly(lactic-co-glycolic acid) nanocapsules: a novel dual-targeted ultrasound contrast agent

Int J Nanomedicine. 2018 Mar 21:13:1791-1807. doi: 10.2147/IJN.S153993. eCollection 2018.

Abstract

Background: The development of nanoscale molecularly targeted ultrasound contrast agents (UCAs) with high affinity and specificity is critical for ultrasound molecular imaging in the early detection of breast cancer.

Purpose: To prospectively evaluate ultrasound molecular imaging with dual-targeted gold nanoshelled poly(lactide-co-glycolic acid) nanocapsules carrying vascular endothelial growth factor receptor type 2 (VEGFR2) and p53 antibodies (DNCs) in MCF-7 orthotopic mice model.

Methods: DNCs were fabricated with an inner PLGA and outer gold nanoshell spherical structure. Its targeting capabilities were evaluated by confocal laser scanning microscopy (CLSM) and flow cytometry (FCM) in vitro. Contrast-enhanced ultrasound imaging (CEUS) with DNCs was evaluated qualitatively and quantitatively in vitro and in MCF-7 orthotopic mice model by two different systems. The biodistribution of NCs in mice was preliminary investigated. Differences were calculated by using analysis of variance.

Results: DNCs showed a well-defined spherical morphology with an average diameter of 276.90±110.50 nm. In vitro, DNCs exhibited high target specificities (79.01±5.63% vs. 2.11±1.07%, P<0.01; 75.54±6.58% vs. 5.21±3.12%, P<0.01) in VEGFR2- and p53-positive cells compared with control cells. In vivo, CEUS displayed a significantly higher video intensity in two systems using DNCs in comparison with non-targeted PLGA@Au NCs and single-targeted NCs. Biodistribution studies revealed that more DNCs in breast cancer tissue could be detected in mice than in other NCs (P<0.05).

Conclusion: DNCs were demonstrated to be novel dual-targeted UCAs and may have potential applications in early non-invasive visualization of breast cancer.

Keywords: antibody; breast cancer; poly(lactic-co-glycolic acid); targeted ultrasound contrast agent; ultrasound molecular imaging.

MeSH terms

  • Animals
  • Antibodies / chemistry
  • Breast Neoplasms / diagnostic imaging*
  • Contrast Media / chemistry*
  • Contrast Media / pharmacokinetics
  • Contrast Media / therapeutic use
  • Female
  • Gold / chemistry
  • Humans
  • Lactic Acid / chemistry*
  • MCF-7 Cells
  • Mice, Inbred BALB C
  • Microscopy, Confocal
  • Molecular Imaging / methods*
  • Nanocapsules / chemistry
  • Nanoshells / chemistry
  • Polyglycolic Acid / chemistry*
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Tissue Distribution
  • Tumor Suppressor Protein p53 / immunology
  • Ultrasonography / methods*
  • Vascular Endothelial Growth Factor Receptor-2 / chemistry

Substances

  • Antibodies
  • Contrast Media
  • Nanocapsules
  • TP53 protein, human
  • Tumor Suppressor Protein p53
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Polyglycolic Acid
  • Lactic Acid
  • Gold
  • KDR protein, human
  • Vascular Endothelial Growth Factor Receptor-2