In vivo characterization of dynein-driven nanovectors using Drosophila oocytes

PLoS One. 2013 Dec 12;8(12):e82908. doi: 10.1371/journal.pone.0082908. eCollection 2013.

Abstract

Molecular motors transport various cargoes including vesicles, proteins and mRNAs, to distinct intracellular compartments. A significant challenge in the field of nanotechnology is to improve drug nuclear delivery by engineering nanocarriers transported by cytoskeletal motors. However, suitable in vivo models to assay transport and delivery efficiency remain very limited. Here, we develop a fast and genetically tractable assay to test the efficiency and dynamics of fluospheres (FS) using microinjection into Drosophila oocytes coupled with time-lapse microscopy. We designed dynein motor driven FS using a collection of dynein light chain 8 (LC8) peptide binding motifs as molecular linkers and characterized in real time the efficiency of the FS movement according to its linker's sequence. Results show that the conserved LC8 binding motif allows fast perinuclear nanoparticle's accumulation in a microtubule and dynein dependent mechanism. These data reveal the Drosophila oocyte as a new valuable tool for the design of motor driven nanovectors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biological Transport, Active / drug effects
  • Cytoskeleton / metabolism*
  • Drosophila Proteins / chemistry*
  • Drosophila Proteins / metabolism
  • Drosophila melanogaster
  • Drug Delivery Systems*
  • Dyneins / chemistry*
  • Dyneins / metabolism
  • Nanoparticles / chemistry*
  • Oocytes / cytology
  • Oocytes / metabolism*

Substances

  • Drosophila Proteins
  • Dyneins

Grants and funding

The authors acknowledge research support from the "Centre National de la Recherche Scientifique", the "Ministère de la Recherche et de l'Enseignement Supérieur", the "Agence Nationale de la Recherche" (program ANR-09-BLAN-0113), the "Association Française contre les Myopathies". The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.