title: A single-molecule approach to explore binding, uptake and transport of cancer cell targeting nanotubes.
abstract: In the past decade carbon nanotubes (CNTs) have been widely studied as a potential drug-delivery system, especially with functionality for cellular targeting. Yet, little is known about the actual process of docking to cell receptors and transport dynamics after internalization. Here we performed single-particle studies of folic acid (FA) mediated CNT binding to human carcinoma cells and their transport inside the cytosol. In particular, we employed molecular recognition force spectroscopy, an atomic force microscopy based method, to visualize and quantify docking of FA functionalized CNTs to FA binding receptors in terms of binding probability and binding force. We then traced individual fluorescently labeled, FA functionalized CNTs after specific uptake, and created a dynamic 'roadmap' that clearly showed trajectories of directed diffusion and areas of nanotube confinement in the cytosol. Our results demonstrate the potential of a single-molecule approach for investigation of drug-delivery vehicles and their targeting capacity.
authors.affiliation: Institute of Biophysics, Johannes Kepler University, A-4020 Linz, Austria. Institute of Materials Science, Christian-Albrechts-University of Kiel, D-24114 Kiel, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Lamprecht
authors.forename: B
authors.initials: B
authors.lastname: Plochberger
authors.forename: V
authors.initials: V
authors.lastname: Ruprecht
authors.forename: S
authors.initials: S
authors.lastname: Wieser
authors.forename: C
authors.initials: C
authors.lastname: Rankl
authors.forename: E
authors.initials: E
authors.lastname: Heister
authors.forename: B
authors.initials: B
authors.lastname: Unterauer
authors.forename: M
authors.initials: M
authors.lastname: Brameshuber
authors.forename: J
authors.initials: J
authors.lastname: Danzberger
authors.forename: P
authors.initials: P
authors.lastname: Lukanov
authors.forename: E
authors.initials: E
authors.lastname: Flahaut
authors.forename: G
authors.initials: G
authors.lastname: Schütz
authors.forename: P
authors.initials: P
authors.lastname: Hinterdorfer
authors.forename: A
authors.initials: A
authors.lastname: Ebner
mesh_terms: D045744:Cell Line, Tumor; D003600:Cytosol / Q000473:pathology*; D016503:Drug Delivery Systems / Q000379:methods*; D005492:Folic Acid / Q000737:chemistry* / Q000494:pharmacology; D006801:Humans; D018625:Microscopy, Atomic Force; D062105:Molecular Docking Simulation; D037742:Nanotubes, Carbon / Q000737:chemistry*; D015739:Nocodazole / Q000494:pharmacology
chemical_list: D037742:Nanotubes, Carbon; D005492:Folic Acid; D015739:Nocodazole