Lobatto Mark E, Calcagno Claudia, Millon Antoine, Senders Max L, Fay Francois, Robson Philip M, Ramachandran Sarayu, Binderup Tina, Paridaans Maarten P M, Sensarn Steven, Rogalla Stephan, Gordon Ronald E, Cardoso Luis, Storm Gert, Metselaar Josbert M, Contag Christopher H, Stroes Erik S G, Fayad Zahi A, Mulder Willem J M
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.
ACS Nano. 2015 Feb 24;9(2):1837-47. doi: 10.1021/nn506750r. Epub 2015 Jan 28.
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.
动脉粥样硬化是全球发病和死亡的主要原因，新型靶向治疗可能会带来益处。最近的研究表明，纳米颗粒可实现高效且局部的药物递送，尽管动脉粥样硬化的纳米颗粒靶向机制尚未完全阐明。在此，我们利用体内和体外多模态成像技术，在兔模型中检测了荧光标记脂质体纳米颗粒的血管壁通透性和动脉粥样硬化斑块蓄积情况。我们发现，通过体内动态对比增强磁共振成像确定的通透性与纳米颗粒斑块蓄积以及随后纳米颗粒在整个血管壁中的分布之间存在很强的相关性。这些关键发现将推动动脉粥样硬化纳米治疗策略的发展。
