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Immune cell screening of a nanoparticle library improves atherosclerosis therapy.
Tang, Jun; Baxter, Samantha; Menon, Arjun; Alaarg, Amr; Sanchez-Gaytan, Brenda L; Fay, Francois; Zhao, Yiming; Ouimet, Mireille; Braza, Mounia S; Longo, Valerie A; Abdel-Atti, Dalya; Duivenvoorden, Raphael; Calcagno, Claudia; Storm, Gert; Tsimikas, Sotirios; Moore, Kathryn J; Swirski, Filip K; Nahrendorf, Matthias; Fisher, Edward A; Pérez-Medina, Carlos; Fayad, Zahi A; Reiner, Thomas; Mulder, Willem J M.
Affiliation
  • Tang J; Translational and Molecular Imaging Institute, Icahn School of Medicine at Mount Sinai, 1470 Madison Avenue, New York, NY 10029.
  • Baxter S; Department of Radiology, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10065.
  • Menon A; Translational and Molecular Imaging Institute, Icahn School of Medicine at Mount Sinai, 1470 Madison Avenue, New York, NY 10029.
  • Alaarg A; Division of Cardiology, Department of Medicine, Marc and Ruti Bell Program in Vascular Biology, New York University School of Medicine, 550 First Avenue, New York, NY 10016.
  • Sanchez-Gaytan BL; Translational and Molecular Imaging Institute, Icahn School of Medicine at Mount Sinai, 1470 Madison Avenue, New York, NY 10029.
  • Fay F; Department of Biomaterials Science and Technology, MIRA Institute for Biomedical Technology and Technical Medicine, University of Twente, 7500 AE Enschede, The Netherlands.
  • Zhao Y; Translational and Molecular Imaging Institute, Icahn School of Medicine at Mount Sinai, 1470 Madison Avenue, New York, NY 10029.
  • Ouimet M; Translational and Molecular Imaging Institute, Icahn School of Medicine at Mount Sinai, 1470 Madison Avenue, New York, NY 10029.
  • Braza MS; Translational and Molecular Imaging Institute, Icahn School of Medicine at Mount Sinai, 1470 Madison Avenue, New York, NY 10029.
  • Longo VA; Division of Cardiology, Department of Medicine, Marc and Ruti Bell Program in Vascular Biology, New York University School of Medicine, 550 First Avenue, New York, NY 10016.
  • Abdel-Atti D; Translational and Molecular Imaging Institute, Icahn School of Medicine at Mount Sinai, 1470 Madison Avenue, New York, NY 10029.
  • Duivenvoorden R; Small-Animal Imaging Core Facility, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10065.
  • Calcagno C; Department of Radiology, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10065.
  • Storm G; Translational and Molecular Imaging Institute, Icahn School of Medicine at Mount Sinai, 1470 Madison Avenue, New York, NY 10029.
  • Tsimikas S; Translational and Molecular Imaging Institute, Icahn School of Medicine at Mount Sinai, 1470 Madison Avenue, New York, NY 10029.
  • Moore KJ; Department of Biomaterials Science and Technology, MIRA Institute for Biomedical Technology and Technical Medicine, University of Twente, 7500 AE Enschede, The Netherlands.
  • Swirski FK; Department of Pharmaceutics, Utrecht Institute of Pharmaceutical Sciences, Utrecht University, 3584 CG Utrecht, The Netherlands.
  • Nahrendorf M; Sulpizio Cardiovascular Center, Department of Medicine, University of California, San Diego, 9434 Medical Center Drive, La Jolla, CA 92037.
  • Fisher EA; Division of Cardiology, Department of Medicine, Marc and Ruti Bell Program in Vascular Biology, New York University School of Medicine, 550 First Avenue, New York, NY 10016.
  • Pérez-Medina C; Center for Systems Biology, Massachusetts General Hospital and Harvard Medical School, Simches Research Building, 185 Cambridge Street, Boston, MA 02114.
  • Fayad ZA; Center for Systems Biology, Massachusetts General Hospital and Harvard Medical School, Simches Research Building, 185 Cambridge Street, Boston, MA 02114.
  • Reiner T; Division of Cardiology, Department of Medicine, Marc and Ruti Bell Program in Vascular Biology, New York University School of Medicine, 550 First Avenue, New York, NY 10016.
  • Mulder WJ; Translational and Molecular Imaging Institute, Icahn School of Medicine at Mount Sinai, 1470 Madison Avenue, New York, NY 10029.
Proc Natl Acad Sci U S A ; 113(44): E6731-E6740, 2016 11 01.
Article in En | MEDLINE | ID: mdl-27791119
ABSTRACT
Immunological complexity in atherosclerosis warrants targeted treatment of specific inflammatory cells that aggravate the disease. With the initiation of large phase III trials investigating immunomodulatory drugs for atherosclerosis, cardiovascular disease treatment enters a new era. We here propose a radically different

approach:

implementing and evaluating in vivo a combinatorial library of nanoparticles with distinct physiochemical properties and differential immune cell specificities. The library's nanoparticles are based on endogenous high-density lipoprotein, which can preferentially deliver therapeutic compounds to pathological macrophages in atherosclerosis. Using the apolipoprotein E-deficient (Apoe-/-) mouse model of atherosclerosis, we quantitatively evaluated the library's immune cell specificity by combining immunological techniques and in vivo positron emission tomography imaging. Based on this screen, we formulated a liver X receptor agonist (GW3965) and abolished its liver toxicity while still preserving its therapeutic function. Screening the immune cell specificity of nanoparticles can be used to develop tailored therapies for atherosclerosis and other inflammatory diseases.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Atherosclerosis / Nanoparticles / Immunotherapy Type of study: Diagnostic_studies / Screening_studies Limits: Animals Language: En Journal: Proc Natl Acad Sci U S A Year: 2016 Type: Article
Fulltext
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Atherosclerosis / Nanoparticles / Immunotherapy Type of study: Diagnostic_studies / Screening_studies Limits: Animals Language: En Journal: Proc Natl Acad Sci U S A Year: 2016 Type: Article