期刊
NANOMEDICINE-NANOTECHNOLOGY BIOLOGY AND MEDICINE
卷 29, 期 -, 页码 -出版社
ELSEVIER
DOI: 10.1016/j.nano.2020.102274
关键词
Atherothrombosis; Drug delivery; Shear stress; Glycoprotein VI; Hemodynamics
资金
- Israel Science Foundation [ISF] [902/18]
- Deutsche Forschungsgemeinschaft [Forschungsgruppe-KFO-274]
- Deutsche Forschungsgemeinschaft [DFG, German Research Foundation] [374031971-TRR 240]
Thrombus formation at athero-thrombotic sites is initiated by the exposure of collagen followed by platelet adhesion mediated by the platelet-specific collagen receptor glycoprotein VI (GPVI). Here, dimeric GPVI was used as a targeting motif to functionalize polymeric nanoparticle-based drug carriers and to show that with proper design, such GPVI-coated nanoparticles (GPNs) can efficiently and specifically target arterial injury sites while withstanding physiological flow. In a microfluidic model, under physiological shear levels (1-40 dyne/cm2), 200 nm and 2 mu m GPNs exhibited a >60 and >10-fold increase in binding to collagen compared to control particles, respectively. In vitro experiments in an arterial stenosis injury model, subjected to physiological pulsatile flow, showed shear-enhanced adhesion of 200 nm GPNs at the stenosis region which was confirmed in vivo in a mice ligation carotid injury model using intravital microscopy. Altogether, our results illustrate how engineering tools can be harnessed to design nano-carriers that efficiently target cardiovascular disease sites. (c) 2020 Elsevier Inc. All rights reserved.
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