title: Translocation of flexible polymersomes across pores at the nanoscale.
abstract: Hierarchical biological systems such as tissues and organs are often characterised by highly crowded and packed environments with nanoscopic interconnections between them. Engineering nanovectors that can penetrate and diffuse across these is critical to ensure enhanced delivery and targeting. Here we demonstrate that flexible polymeric vesicles, known as polymersomes, enable the translocation of large macromolecules across both synthetic and biological porous systems. We compare the translocation across narrow pores of different polymersome formulations. We demonstrate that effective translocation depends on the right combination of mechanical properties and surface lubrication. We prove that with the effect of external gradients (e.g. osmotic pressure, capillarity, hydration, etc.) polymersomes can translocate across pores with diameters one order of magnitude smaller without breaking. We demonstrate that these properties are essential to develop effective tissue penetration and show polymersome mediated transdermal delivery of large macromolecules such as dextran and antibodies using human ex vivo skin.
authors.affiliation: Department of Biomedical Sciences, University of Sheffield, Sheffield, UK and The Kroto Research Institute, University of Sheffield, Sheffield, UK and Department of Material Science and Engineering, University of Sheffield, Sheffield, UK.
authors.forename: Carla
authors.initials: C
authors.lastname: Pegoraro
authors.affiliation: Department of Chemistry, University College London, London, UK and The MRC/UCL Centre for Medical Molecular Virology, University College London, London, UK. g.battaglia@ucl.ac.uk and Biocompatibles UK Ltd, Farnham, UK.
authors.forename: Denis
authors.initials: D
authors.lastname: Cecchin
authors.affiliation: Department of Biomedical Sciences, University of Sheffield, Sheffield, UK and Department of Chemistry, University of Sheffield, Sheffield, UK.
authors.forename: Jeppe
authors.initials: J
authors.lastname: Madsen
authors.affiliation: Department of Chemistry, University of Sheffield, Sheffield, UK.
authors.forename: Nicholas
authors.initials: N
authors.lastname: Warren
authors.affiliation: Department of Chemistry, University of Sheffield, Sheffield, UK.
authors.forename: Steven P
authors.initials: SP
authors.lastname: Armes
authors.affiliation: The Kroto Research Institute, University of Sheffield, Sheffield, UK and Department of Material Science and Engineering, University of Sheffield, Sheffield, UK.
authors.forename: Sheila
authors.initials: S
authors.lastname: MacNeil
authors.affiliation: Biocompatibles UK Ltd, Farnham, UK.
authors.forename: Andrew
authors.initials: A
authors.lastname: Lewis
authors.affiliation: Department of Chemistry, University of Sheffield, Sheffield, UK and Department of Chemistry, University College London, London, UK and The MRC/UCL Centre for Medical Molecular Virology, University College London, London, UK. g.battaglia@ucl.ac.uk.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Battaglia