Reversal of Vascular Calcification and Aneurysms in a Rat Model Using Dual Targeted Therapy with EDTA- and PGG-Loaded Nanoparticles

Theranostics. 2016 Aug 18;6(11):1975-1987. doi: 10.7150/thno.16547. eCollection 2016.

Abstract

Degeneration of elastic lamina and vascular calcification are common features of vascular pathology such as aortic aneurysms. We tested whether dual therapy with targeted nanoparticles (NPs) can remove mineral deposits (by delivery of a chelating agent, ethylene diamine tetraacetic acid (EDTA)) and restore elastic lamina (by delivery of a polyphenol, pentagalloyl glucose (PGG)) to reverse moderate aneurysm development. EDTA followed by PGG NP delivery led to reduction in macrophage recruitment, matrix metalloproteinase (MMP) activity, elastin degradation and calcification in the aorta as compared to delivery of control blank NPs. Such dual therapy restored vascular elastic lamina and improved vascular function as observed by improvement in circumferential strain. Therefore, dual targeted therapy may be an attractive option to remove mineral deposits and restore healthy arterial structures in moderately developed aneurysms.

Keywords: AAA; PGG.; calcification; chelation therapy; elastin.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Aortic Aneurysm / drug therapy*
  • Aortic Aneurysm / pathology
  • Arachnida
  • Calcium Chelating Agents / administration & dosage*
  • Disease Models, Animal
  • Drug Therapy, Combination
  • Edetic Acid / administration & dosage*
  • Histocytochemistry
  • Hydrolyzable Tannins / administration & dosage*
  • Nanoparticles / administration & dosage*
  • Polyphenols / administration & dosage*
  • Rats
  • Treatment Outcome
  • Vascular Calcification / drug therapy*
  • Vascular Calcification / pathology

Substances

  • Calcium Chelating Agents
  • Hydrolyzable Tannins
  • Polyphenols
  • pentagalloylglucose
  • Edetic Acid