title: Targeting distinct myeloid cell populations in vivo using polymers, liposomes and microbubbles.
abstract: Identifying intended or accidental cellular targets for drug delivery systems is highly relevant for evaluating therapeutic and toxic effects. However, limited knowledge exists on the distribution of nano- and micrometer-sized carrier systems at the cellular level in different organs. We hypothesized that clinically relevant carrier materials, differing in composition and size, are able to target distinct myeloid cell subsets that control inflammatory processes, such as macrophages, neutrophils, monocytes and dendritic cells. Therefore, we analyzed the biodistribution and in vivo cellular uptake of intravenously injected poly(N-(2-hydroxypropyl) methacrylamide) polymers, PEGylated liposomes and poly(butyl cyanoacrylate) microbubbles in mice, using whole-body imaging (computed tomography - fluorescence-mediated tomography), intra-organ imaging (intravital multi-photon microscopy) and cellular analysis (flow cytometry of blood, liver, spleen, lung and kidney). While the three carrier materials shared accumulation in tissue macrophages in liver and spleen, they notably differed in uptake by other myeloid subsets. Kupffer cells and splenic red pulp macrophages rapidly take up microbubbles. Liposomes efficiently reach dendritic cells in liver, lung and kidney. Polymers exhibit the longest circulation half-life and target endothelial cells in the liver, neutrophils and alveolar macrophages. The identification of such previously unrecognized target cell populations might open up new avenues for more efficient drug delivery.
authors.affiliation: Department of Medicine III, University Hospital Aachen, Aachen, Germany.
authors.forename: Can
authors.initials: C
authors.lastname: Ergen
authors.affiliation: Department of Medicine III, University Hospital Aachen, Aachen, Germany.
authors.forename: Felix
authors.initials: F
authors.lastname: Heymann
authors.affiliation: Department of Experimental Molecular Imaging, University Clinic and Helmholtz Institute for Biomedical Engineering, RWTH Aachen University, Aachen, Germany.
authors.forename: Wa'el
authors.initials: W
authors.lastname: Al Rawashdeh
authors.affiliation: Department of Experimental Molecular Imaging, University Clinic and Helmholtz Institute for Biomedical Engineering, RWTH Aachen University, Aachen, Germany.
authors.forename: Felix
authors.initials: F
authors.lastname: Gremse
authors.affiliation: Department of Medicine III, University Hospital Aachen, Aachen, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Bartneck
authors.affiliation: Department of Medicine III, University Hospital Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Ulf
authors.initials: U
authors.lastname: Panzer
authors.affiliation: Institute of Macromolecular Chemistry, Academy of Sciences of the Czech Republic, Prague, Czechia.
authors.forename: Robert
authors.initials: R
authors.lastname: Pola
authors.affiliation: Institute of Macromolecular Chemistry, Academy of Sciences of the Czech Republic, Prague, Czechia.
authors.forename: Michal
authors.initials: M
authors.lastname: Pechar
authors.affiliation: Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands; Department of Targeted Therapeutics, MIRA Institute for Biomedical Technology and Technical Medicine, University of Twente, Enschede, The Netherlands.
authors.forename: Gert
authors.initials: G
authors.lastname: Storm
authors.affiliation: Institute of Organic Chemistry, Johannes Gutenberg University, Mainz, Germany.
authors.forename: Nicole
authors.initials: N
authors.lastname: Mohr
authors.affiliation: Institute of Organic Chemistry, Johannes Gutenberg University, Mainz, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Barz
authors.affiliation: Institute of Organic Chemistry, Johannes Gutenberg University, Mainz, Germany.
authors.forename: Rudolf
authors.initials: R
authors.lastname: Zentel
authors.affiliation: Department of Experimental Molecular Imaging, University Clinic and Helmholtz Institute for Biomedical Engineering, RWTH Aachen University, Aachen, Germany.
authors.forename: Fabian
authors.initials: F
authors.lastname: Kiessling
authors.affiliation: Department of Medicine III, University Hospital Aachen, Aachen, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Trautwein
authors.affiliation: Department of Experimental Molecular Imaging, University Clinic and Helmholtz Institute for Biomedical Engineering, RWTH Aachen University, Aachen, Germany; Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands; Department of Targeted Therapeutics, MIRA Institute for Biomedical Technology and Technical Medicine, University of Twente, Enschede, The Netherlands. Electronic address: tlammers@ukaachen.de.
authors.forename: Twan
authors.initials: T
authors.lastname: Lammers
authors.affiliation: Department of Medicine III, University Hospital Aachen, Aachen, Germany. Electronic address: frank.tacke@gmx.net.
authors.forename: Frank
authors.initials: F
authors.lastname: Tacke
mesh_terms: D000818:Animals; D002214:Capsules / Q000008:administration & dosage / Q000737:chemistry*; D008081:Liposomes / Q000737:chemistry*; D008422:Materials Testing; D051379:Mice; D008819:Mice, Nude; D045423:Microbubbles / Q000627:therapeutic use; D058990:Molecular Targeted Therapy / Q000379:methods*; D022423:Myeloid Cells / Q000737:chemistry* / Q000166:cytology; D053769:Nanocapsules / Q000008:administration & dosage / Q000737:chemistry*; D009928:Organ Specificity; D011108:Polymers / Q000737:chemistry*; D014018:Tissue Distribution; D014781:Viscera / Q000737:chemistry* / Q000166:cytology
chemical_list: D002214:Capsules; D008081:Liposomes; D053769:Nanocapsules; D011108:Polymers
keywords: Liposomes; Macrophages; Microbubbles; Nanomedicine; Polymers; Targeted delivery