Abstract 1162: avb3-Integrin-targeted Paramagnetic Nanoparticles Deliver Rapamycin into the Vascular Wall and Inhibit Stenosis Following Balloon Injury
Background: Perfluorocarbon nanoparticles can be functionalized and targeted to an array of cellular and extracellular intramural vascular biomarkers exposed along sheared tissue planes by balloon stretch injury. The objective of this study was to determine if local, intramural delivery of integrin-targeted perfluorocarbon nanoparticles incorporating rapamycin could inhibit vascular stenosis following balloon overstretch injury.
Methods: Femoral arteries of NZW rabbits on atherogenic diet for 3 weeks were subjected to balloon stretch injury via a catheter approach from the right common carotid artery. One injured arterial segment was infused between snares with paramagnetic αϖβ3-integrin-targeted nanoparticles while the contralateral artery received targeted rapamycin nanoparticles without drug or saline. The delivery of the paramagnetic nanoparticles was confirmed noninvasively via T1-weighted MRI contrast enhancement in a 1.5 T MR scanner. After two weeks, neointimal plaque development was assessed by repeat MR angiography and by serial microscopic quantification of arterial cross sections.
Results: Contrast enhancement with avb3-targeted nanoparticles allowed the localization and quantification of vascular wall injury, which was undetectable with conventional MR and X-ray angiography. Intramural delivery of avb3-integrin-targeted paramagnetic nanoparticles inhibited iliac stenosis two weeks following balloon injury by 34% and 42% compared to contralateral segments exposed to avb3-integrin-targeted nanoparticles without drug and the saline controls, respectively. No difference (P > 0.05) was observed between vessels exposed to αvβ3-integrin-targeted nanoparticles without drug or saline.
Conclusions: Intramurally targeted nanoparticles present a new approach to extend the antirestenotic benefits of rapamycin to lesions not amenable to DES deployment, particularly in emerging MR interventional procedures.