한빛사논문
- 조회2,607
Abstract
YongTae Kima,1, Mark E. Lobattob,c,1, Tomohiro Kawaharad, Bomy Lee Chunge,f, Aneta J. Mieszawskab, Brenda L. Sanchez-Gaytanb, Francois Fayb, Max L. Sendersb, Claudia Calcagnob, Jacob Becraftg, May Tun Saungh, Ronald E. Gordoni, Erik S. G. Stroesc, Mingming Mae, Omid C. Farokhzadj, Zahi A. Fayadb, Willem J. M. Mulderb,c,2, and Robert Langere,f,g,k,2
aThe George W. Woodruff School of Mechanical Engineering, Institute for Electronics and Nanotechnology, Parker H. Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, GA 30332;
bTranslational and Molecular Imaging Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029;
cDepartment of Vascular Medicine, Academic Medical Center, 1105 AZ, Amsterdam, The Netherlands;
dDepartment of Biological Functions and Engineering, Kyushu Institute of Technology, Fukuoka 804-8550, Japan;
eDavid H. Koch Institute for Integrative Cancer Research,
fDepartment of Chemical Engineering,
gDepartment of Biological Engineering, and
kHarvard–MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, MA 02139;
hBoston University School of Medicine, Boston, MA 02215;
iDepartment of Pathology, Mount Sinai Hospital, New York, NY 10029; and
jDepartment of Anesthesiology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02215
Abstract
Therapeutic and diagnostic nanomaterials are being intensely studied for several diseases, including cancer and atherosclerosis. However, the exact mechanism by which nanomedicines accumulate at targeted sites remains a topic of investigation, especially in the context of atherosclerotic disease. Models to accurately predict transvascular permeation of nanomedicines are needed to aid in design optimization. Here we show that an endothelialized microchip with controllable permeability can be used to probe nanoparticle translocation across an endothelial cell layer. To validate our in vitro model, we studied nanoparticle translocation in an in vivo rabbit model of atherosclerosis using a variety of preclinical and clinical imaging methods. Our results reveal that the translocation of lipid-polymer hybrid nanoparticles across the atherosclerotic endothelium is dependent on microvascular permeability. These results were mimicked with our microfluidic chip, demonstrating the potential utility of the model system.
nanotechnology, cardiovascular disease, microfluidics, noninvasive imaging
1Y.K. and M.E.L. contributed equally to this work.
2To whom correspondence may be addressed.
Author contributions: Y.K., M.E.L., W.J.M.M., and R.L. designed research; Y.K., M.E.L., T.K., B.L.C., A.J.M., B.L.S.-G., F.F., M.L.S., C.C., J.B., and M.T.S. performed research; Y.K., M.E.L., T.K., B.L.C., A.J.M., B.L.S.-G., R.E.G., E.S.G.S., M.M., O.C.F., Z.A.F., W.J.M.M., and R.L. contributed new reagents/analytic tools; Y.K., M.E.L., T.K., O.C.F., Z.A.F., W.J.M.M., and R.L. analyzed data; and Y.K., M.E.L., W.J.M.M., and R.L. wrote the paper.
논문정보
- Research article
- 2014년 01월 (BRIC 등록일 2014-01-09)
- 국외 연구진
- 바이오·의료융합 > 바이오센싱 및 나노바이오물질
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