Dual-Targeted Theranostic Delivery of miRs Arrests Abdominal Aortic Aneurysm Development

Mol Ther. 2018 Apr 4;26(4):1056-1065. doi: 10.1016/j.ymthe.2018.02.010. Epub 2018 Feb 16.


Abdominal aortic aneurysm (AAA) is an often deadly disease without medical, non-invasive treatment options. The upregulation of vascular cell adhesion molecule-1 (VCAM-1) on aortic endothelium provides an early target epitope for a novel biotechnological theranostic approach. MicroRNA-126 was used as a therapeutic agent, based on its capability to downregulate VCAM-1 expression in endothelial cells and thereby reduces leukocyte adhesion and exerts anti-inflammatory effects. Ultrasound microbubbles were chosen as carriers, allowing both molecular imaging as well as targeted therapy of AAA. Microbubbles were coupled with a VCAM-1-targeted single-chain antibody (scFvmVCAM-1) and a microRNA-126 mimic (M126) constituting theranostic microbubbles (TargMB-M126). TargMB-M126 downregulates VCAM-1 expression in vitro and in an in vivo acute inflammatory murine model. Most importantly, using TargMB-M126 and ultrasound-guided burst delivery of M126, the development of AAA in an angiotensin-II-induced mouse model can be prevented. Overall, we describe a unique biotechnological theranostic approach with the potential for early diagnosis and long-sought-after medical therapy of AAA.

Keywords: abdominal aortic aneurysm; microRNA-126; targeted therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Aortic Aneurysm, Abdominal / genetics*
  • Aortic Aneurysm, Abdominal / metabolism
  • Aortic Aneurysm, Abdominal / pathology*
  • Aortic Aneurysm, Abdominal / therapy
  • Biomarkers
  • Cells, Cultured
  • Disease Models, Animal
  • Endothelial Cells
  • Gene Transfer Techniques
  • Genetic Therapy* / methods
  • Immunohistochemistry
  • Male
  • Mice
  • Mice, Knockout
  • MicroRNAs / administration & dosage
  • MicroRNAs / chemistry
  • MicroRNAs / genetics*
  • Molecular Imaging
  • Single-Chain Antibodies / pharmacology
  • Ultrasonography
  • Vascular Cell Adhesion Molecule-1 / antagonists & inhibitors
  • Vascular Cell Adhesion Molecule-1 / chemistry
  • Vascular Cell Adhesion Molecule-1 / metabolism


  • Biomarkers
  • MicroRNAs
  • Single-Chain Antibodies
  • Vascular Cell Adhesion Molecule-1