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Merck

Atherosclerotic plaque targeting mechanism of long-circulating nanoparticles established by multimodal imaging.

ACS nano (2015-01-27)
Mark E Lobatto, Claudia Calcagno, Antoine Millon, Max L Senders, Francois Fay, Philip M Robson, Sarayu Ramachandran, Tina Binderup, Maarten P M Paridaans, Steven Sensarn, Stephan Rogalla, Ronald E Gordon, Luis Cardoso, Gert Storm, Josbert M Metselaar, Christopher H Contag, Erik S G Stroes, Zahi A Fayad, Willem J M Mulder
ABSTRAKT

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.

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