title: Magnetic antibody-linked nanomatchmakers for therapeutic cell targeting.
abstract: Stem cell transplantation is a promising strategy for therapeutic cardiac regeneration, but current therapies are limited by inefficient interaction between potentially beneficial cells (either exogenously transplanted or endogenously recruited) and the injured tissue. Here we apply targeted nanomedicine to achieve in vivo cell-mediated tissue repair, imaging and localized enrichment without cellular transplantation. Iron nanoparticles are conjugated with two types of antibodies (one against antigens on therapeutic cells and the other directed at injured cells) to produce magnetic bifunctional cell engager (MagBICE). The antibodies link the therapeutic cells to the injured cells, whereas the iron core of MagBICE enables physical enrichment and imaging. We treat acute myocardial infarction by targeting exogenous bone marrow-derived stem cells (expressing CD45) or endogenous CD34-positive cells to injured cardiomyocytes (expressing myosin light chain. Targeting can be further enhanced by magnetic attraction, leading to augmented functional benefits. MagBICE represents a generalizable platform technology for regenerative medicine.
authors.affiliation: 1] Cedars-Sinai Heart Institute, 8700 Beverly Boulevard, Los Angeles, California 90048, USA [2] Department of Molecular Biomedical Sciences, Center for Comparative Medicine and Translational Research, College of Veterinary Medicine, 1060 William Moore Drive, North Carolina State University, Raleigh, North Carolina 27607, USA [3] Joint Department of Biomedical Engineering, University of North Carolina at Chapel Hill and North Carolina State University, Raleigh, North Carolina 27607, USA.
authors.forename: Ke
authors.initials: K
authors.lastname: Cheng
authors.affiliation: Department of Cardiology, First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, China.
authors.forename: Deliang
authors.initials: D
authors.lastname: Shen
authors.affiliation: Department of Molecular Biomedical Sciences, Center for Comparative Medicine and Translational Research, College of Veterinary Medicine, 1060 William Moore Drive, North Carolina State University, Raleigh, North Carolina 27607, USA.
authors.forename: M Taylor
authors.initials: MT
authors.lastname: Hensley
authors.affiliation: Cedars-Sinai Heart Institute, 8700 Beverly Boulevard, Los Angeles, California 90048, USA.
authors.forename: Ryan
authors.initials: R
authors.lastname: Middleton
authors.affiliation: Cedars-Sinai Heart Institute, 8700 Beverly Boulevard, Los Angeles, California 90048, USA.
authors.forename: Baiming
authors.initials: B
authors.lastname: Sun
authors.affiliation: Cedars-Sinai Heart Institute, 8700 Beverly Boulevard, Los Angeles, California 90048, USA.
authors.forename: Weixin
authors.initials: W
authors.lastname: Liu
authors.affiliation: Cedars-Sinai Heart Institute, 8700 Beverly Boulevard, Los Angeles, California 90048, USA.
authors.forename: Geoffrey
authors.initials: G
authors.lastname: De Couto
authors.affiliation: Cedars-Sinai Heart Institute, 8700 Beverly Boulevard, Los Angeles, California 90048, USA.
authors.forename: Eduardo
authors.initials: E
authors.lastname: Marbán
mesh_terms: D000818:Animals; D000906:Antibodies; D001854:Bone Marrow Cells / Q000378:metabolism*; D016026:Bone Marrow Transplantation / Q000379:methods*; D002465:Cell Movement; D052203:Ferrosoferric Oxide / Q000627:therapeutic use*; D007501:Iron; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D059346:Magnets; D009203:Myocardial Infarction / Q000628:therapy*; D032383:Myocytes, Cardiac / Q000378:metabolism*; D036103:Nanotechnology / Q000379:methods*; D051381:Rats; D012038:Regeneration; D013234:Stem Cells
chemical_list: D000906:Antibodies; D007501:Iron; D052203:Ferrosoferric Oxide