A modular approach toward producing nanotherapeutics targeting the innate immune system.

Autor:	van Leent MMT; Biomedical Engineering and Imaging Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.; Department of Medical Biochemistry, Amsterdam University Medical Centers, Amsterdam, Netherlands., Meerwaldt AE; Biomedical Engineering and Imaging Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.; Biomedical MR Imaging and Spectroscopy Group, Center for Image Sciences, University Medical Center Utrecht/Utrecht University, Utrecht, Netherlands., Berchouchi A; Biomedical Engineering and Imaging Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA., Toner YC; Biomedical Engineering and Imaging Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA., Burnett ME; Biomedical Engineering and Imaging Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA., Klein ED; Biomedical Engineering and Imaging Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA., Verschuur AVD; Biomedical Engineering and Imaging Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA., Nauta SA; Biomedical Engineering and Imaging Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA., Munitz J; Biomedical Engineering and Imaging Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA., Prévot G; Biomedical Engineering and Imaging Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA., van Leeuwen EM; Biomedical Engineering and Imaging Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA., Ordikhani F; Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA., Mourits VP; Department of Internal Medicine, Radboud Center for Infectious Diseases (RCI), Radboud Institute of Molecular Life Sciences (RIMLS), Radboud University Medical Center, Nijmegen, Netherlands., Calcagno C; Biomedical Engineering and Imaging Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA., Robson PM; Biomedical Engineering and Imaging Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA., Soultanidis G; Biomedical Engineering and Imaging Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA., Reiner T; Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.; Department of Radiology, Weill Cornell Medical College, New York, NY, USA.; Chemical Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Joosten RRM; Center of Multiscale Electron Microscopy, Department of Chemical Engineering and Chemistry, Eindhoven University of Technology, PO Box 513, 5600 MB Eindhoven, Netherlands., Friedrich H; Center of Multiscale Electron Microscopy, Department of Chemical Engineering and Chemistry, Eindhoven University of Technology, PO Box 513, 5600 MB Eindhoven, Netherlands.; Institute for Complex Molecular Systems, Eindhoven University of Technology, Eindhoven, Netherlands., Madsen JC; Center for Transplantation Sciences and Division of Cardiac Surgery, Department of Surgery, Massachusetts General Hospital, Boston, MA, USA., Kluza E; Institute for Complex Molecular Systems, Eindhoven University of Technology, Eindhoven, Netherlands.; Laboratory of Chemical Biology, Department of Biochemical Engineering, Eindhoven University of Technology, Eindhoven, Netherlands., van der Meel R; Institute for Complex Molecular Systems, Eindhoven University of Technology, Eindhoven, Netherlands.; Laboratory of Chemical Biology, Department of Biochemical Engineering, Eindhoven University of Technology, Eindhoven, Netherlands., Joosten LAB; Department of Internal Medicine, Radboud Center for Infectious Diseases (RCI), Radboud Institute of Molecular Life Sciences (RIMLS), Radboud University Medical Center, Nijmegen, Netherlands., Netea MG; Department of Internal Medicine, Radboud Center for Infectious Diseases (RCI), Radboud Institute of Molecular Life Sciences (RIMLS), Radboud University Medical Center, Nijmegen, Netherlands.; Department for Genomics & Immunoregulation, Life and Medical Sciences Institute (LIMES), University of Bonn, Bonn, Germany., Ochando J; Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA., Fayad ZA; Biomedical Engineering and Imaging Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA., Pérez-Medina C; Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain., Mulder WJM; Biomedical Engineering and Imaging Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA. bram.teunissen@mssm.edu willem.mulder@mssm.edu.; Institute for Complex Molecular Systems, Eindhoven University of Technology, Eindhoven, Netherlands.; Laboratory of Chemical Biology, Department of Biochemical Engineering, Eindhoven University of Technology, Eindhoven, Netherlands., Teunissen AJP; Biomedical Engineering and Imaging Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA. bram.teunissen@mssm.edu willem.mulder@mssm.edu.
Jazyk:	angličtina
Zdroj:	Science advances [Sci Adv] 2021 Mar 05; Vol. 7 (10). Date of Electronic Publication: 2021 Mar 05 (Print Publication: 2021).
DOI:	10.1126/sciadv.abe7853
Abstrakt:	Immunotherapies controlling the adaptive immune system are firmly established, but regulating the innate immune system remains much less explored. The intrinsic interactions between nanoparticles and phagocytic myeloid cells make these materials especially suited for engaging the innate immune system. However, developing nanotherapeutics is an elaborate process. Here, we demonstrate a modular approach that facilitates efficiently incorporating a broad variety of drugs in a nanobiologic platform. Using a microfluidic formulation strategy, we produced apolipoprotein A1-based nanobiologics with favorable innate immune system-engaging properties as evaluated by in vivo screening. Subsequently, rapamycin and three small-molecule inhibitors were derivatized with lipophilic promoieties, ensuring their seamless incorporation and efficient retention in nanobiologics. A short regimen of intravenously administered rapamycin-loaded nanobiologics (mTORi-NBs) significantly prolonged allograft survival in a heart transplantation mouse model. Last, we studied mTORi-NB biodistribution in nonhuman primates by PET/MR imaging and evaluated its safety, paving the way for clinical translation. (Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).)
Databáze:	MEDLINE
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