title: Influence of Surface Modifications on the Spatiotemporal Microdistribution of Quantum Dots In Vivo.
abstract: For biomedical applications of nanoconstructs, it is a general prerequisite to efficiently reach the desired target site. In this regard, it is crucial to determine the spatiotemporal distribution of nanomaterials at the microscopic tissue level. Therefore, the effect of different surface modifications on the distribution of microinjected quantum dots (QDs) in mouse skeletal muscle tissue has been investigated. In vivo real-time fluorescence microscopy and particle tracking reveal that carboxyl QDs preferentially attach to components of the extracellular matrix (ECM), whereas QDs coated with polyethylene glycol (PEG) show little interaction with tissue constituents. Transmission electron microscopy elucidates that carboxyl QDs adhere to collagen fibers as well as basement membranes, a type of ECM located on the basolateral side of blood vessel walls. Moreover, carboxyl QDs have been found in endothelial junctions as well as in caveolae of endothelial cells, enabling them to translocate into the vessel lumen. The in vivo QD distribution is confirmed by in vitro experiments. The data suggest that ECM components act as a selective barrier depending on QD surface modification. For future biomedical applications, such as targeting of blood vessel walls, the findings of this study offer design criteria for nanoconstructs that meet the requirements of the respective application.
authors.affiliation: Walter Brendel Centre of Experimental Medicine, Ludwig-Maximilians-Universität München, Marchioninistr, 15, 81377, Munich, Germany.
authors.forename: Katharina
authors.initials: K
authors.lastname: Nekolla
authors.affiliation: Department of Pharmacy, Ludwig-Maximilians-Universität München, Butenandtstr. 5-13, 81377, Munich, Germany.
authors.forename: Kerstin
authors.initials: K
authors.lastname: Kick
authors.affiliation: Walter Brendel Centre of Experimental Medicine, Ludwig-Maximilians-Universität München, Marchioninistr, 15, 81377, Munich, Germany.
authors.forename: Sabine
authors.initials: S
authors.lastname: Sellner
authors.affiliation: Max Planck Institute for Molecular Biomedicine, Röntgenstr. 20, 48149, Münster, Germany.
authors.forename: Karina
authors.initials: K
authors.lastname: Mildner
authors.affiliation: Department of Pharmacy, Ludwig-Maximilians-Universität München, Butenandtstr. 5-13, 81377, Munich, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Zahler
authors.affiliation: Max Planck Institute for Molecular Biomedicine, Röntgenstr. 20, 48149, Münster, Germany.
authors.forename: Dagmar
authors.initials: D
authors.lastname: Zeuschner
authors.affiliation: Walter Brendel Centre of Experimental Medicine, Ludwig-Maximilians-Universität München, Marchioninistr, 15, 81377, Munich, Germany.
authors.forename: Fritz
authors.initials: F
authors.lastname: Krombach
authors.affiliation: Walter Brendel Centre of Experimental Medicine, Ludwig-Maximilians-Universität München, Marchioninistr, 15, 81377, Munich, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Rehberg
mesh_terms: D000818:Animals; D001808:Blood Vessels / Q000737:chemistry* / Q000648:ultrastructure; D042783:Endothelial Cells / Q000737:chemistry* / Q000648:ultrastructure; D005109:Extracellular Matrix / Q000737:chemistry* / Q000648:ultrastructure; D007273:Injections, Intramuscular; D051379:Mice; D008810:Mice, Inbred C57BL; D008845:Microinjections; D010316:Particle Size; D045663:Quantum Dots / Q000008:administration & dosage / Q000737:chemistry* / Q000648:ultrastructure*; D062211:Spatio-Temporal Analysis; D013329:Structure-Activity Relationship; D013499:Surface Properties; D014018:Tissue Distribution
keywords: endothelial cells; extracellular matrix; in vivo microscopy; nanoparticles; transcytosis