title: Atherosclerotic plaque targeting mechanism of long-circulating nanoparticles established by multimodal imaging.
abstract: Atherosclerosis is a major cause of global morbidity and mortality that could benefit from novel targeted therapeutics. Recent studies have shown efficient and local drug delivery with nanoparticles, although the nanoparticle targeting mechanism for atherosclerosis has not yet been fully elucidated. Here we used in vivo and ex vivo multimodal imaging to examine permeability of the vessel wall and atherosclerotic plaque accumulation of fluorescently labeled liposomal nanoparticles in a rabbit model. We found a strong correlation between permeability as established by in vivo dynamic contrast enhanced magnetic resonance imaging and nanoparticle plaque accumulation with subsequent nanoparticle distribution throughout the vessel wall. These key observations will enable the development of nanotherapeutic strategies for atherosclerosis.
authors.affiliation: Translational and Molecular Imaging Institute, Department of Radiology, Icahn School of Medicine at Mount Sinai , One Gustave L. Levy Place, New York, New York 10029, United States.
authors.forename: Mark E
authors.initials: ME
authors.lastname: Lobatto
authors.forename: Claudia
authors.initials: C
authors.lastname: Calcagno
authors.forename: Antoine
authors.initials: A
authors.lastname: Millon
authors.forename: Max L
authors.initials: ML
authors.lastname: Senders
authors.forename: Francois
authors.initials: F
authors.lastname: Fay
authors.forename: Philip M
authors.initials: PM
authors.lastname: Robson
authors.forename: Sarayu
authors.initials: S
authors.lastname: Ramachandran
authors.forename: Tina
authors.initials: T
authors.lastname: Binderup
authors.forename: Maarten P M
authors.initials: MP
authors.lastname: Paridaans
authors.forename: Steven
authors.initials: S
authors.lastname: Sensarn
authors.forename: Stephan
authors.initials: S
authors.lastname: Rogalla
authors.forename: Ronald E
authors.initials: RE
authors.lastname: Gordon
authors.forename: Luis
authors.initials: L
authors.lastname: Cardoso
authors.forename: Gert
authors.initials: G
authors.lastname: Storm
authors.forename: Josbert M
authors.initials: JM
authors.lastname: Metselaar
authors.forename: Christopher H
authors.initials: CH
authors.lastname: Contag
authors.forename: Erik S G
authors.initials: ES
authors.lastname: Stroes
authors.forename: Zahi A
authors.initials: ZA
authors.lastname: Fayad
authors.forename: Willem J M
authors.initials: WJ
authors.lastname: Mulder
mesh_terms: D000818:Animals; D002199:Capillary Permeability; D005456:Fluorescent Dyes / Q000737:chemistry; D008297:Male; D064847:Multimodal Imaging / Q000379:methods*; D053758:Nanoparticles / Q000737:chemistry / Q000378:metabolism; D058226:Plaque, Atherosclerotic / Q000097:blood* / Q000175:diagnosis* / Q000378:metabolism; D011817:Rabbits; D013997:Time Factors
chemical_list: D005456:Fluorescent Dyes
keywords: DCE-MRI; atherosclerosis; imaging; in vivo microscopy; nanomedicine; nanoparticle; targeting