A single-molecule approach to explore binding, uptake and transport of cancer cell targeting nanotubes

Constanze Lamprecht (1, 2) , Birgit Plochberger (3) , Verena Ruprecht (4) , Stefan Wieser (4) , Christian Rankl (5) , Elena Heister (6) , Barbara Unterauer (1) , Mario Brameshuber (3) , Jürgen Danzberger (1) , Petar Lukanov (7) , Emmanuel Flahaut (7) , Gerhard Schütz (3, 8) , Peter Hinterdorfer (1) , Andreas Ebner (1)

1 JKU - University of Linz - Johannes Kepler Universität Linz
2 CAU - Christian-Albrechts-Universität zu Kiel = Christian-Albrechts University of Kiel = Université Christian-Albrechts de Kiel
3 TU Wien - Vienna University of Technology = Technische Universität Wien
4 IST Austria - Institute of Science and Technology [Klosterneuburg, Austria]
5 Agilent Technologies
6 UNIS - University of Surrey
7 CIRIMAT - Centre interuniversitaire de recherche et d'ingenierie des matériaux
8 Center for Advanced Bioanalysis - CBL (AUSTRIA)

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.

Mots clés: AFM; Molecular recognition; Force spectroscopy; Carbon nanotubes; Particle tracking

Domaines: Matériaux; Médecine humaine et pathologie; Matériaux

Constanze Lamprecht, Birgit Plochberger, Verena Ruprecht, Stefan Wieser, Christian Rankl, et al.. A single-molecule approach to explore binding, uptake and transport of cancer cell targeting nanotubes. Nanotechnology, 2014, vol. 25 (n° 12), pp.125704. ⟨10.1088/0957-4484/25/12/125704⟩. ⟨hal-01132418⟩