title: TAT and HA2 facilitate cellular uptake of gold nanoparticles but do not lead to cytosolic localisation.
abstract: The methods currently available to deliver functional labels and drugs to the cell cytosol are inefficient and this constitutes a major obstacle to cell biology (delivery of sensors and imaging probes) and therapy (drug access to the cell internal machinery). As cell membranes are impermeable to most molecular cargos, viral peptides have been used to bolster their internalisation through endocytosis and help their release to the cytosol by bursting the endosomal vesicles. However, conflicting results have been reported on the extent of the cytosolic delivery achieved. To evaluate their potential, we used gold nanoparticles as model cargos and systematically assessed how the functionalisation of their surface by either or both of the viral peptides TAT and HA2 influenced their intracellular delivery. We evaluated the number of gold nanoparticles present in cells after internalisation using photothermal microscopy and their subcellular localisation by electron microscopy. While their uptake increased when the TAT and/or HA2 viral peptides were present on their surface, we did not observe a significant cytosolic delivery of the gold nanoparticles.
authors.affiliation: Department of Chemistry, University of Liverpool, Liverpool, United Kingdom; Institute of Integrative Biology, University of Liverpool, Liverpool, United Kingdom; CNRS, UMR 6290, Institute of Genetics and Development of Rennes, Rennes, France; Université de Rennes 1, Université Européenne de Bretagne, Structure fédérative de recherche Biosit, Faculté de Médecine, Rennes, France.
authors.forename: Yann
authors.initials: Y
authors.lastname: Cesbron
authors.affiliation: Institute of Integrative Biology, University of Liverpool, Liverpool, United Kingdom.
authors.forename: Umbreen
authors.initials: U
authors.lastname: Shaheen
authors.affiliation: Institute of Integrative Biology, University of Liverpool, Liverpool, United Kingdom; Institute of Materials Research and Engineering, A*STAR, 3 Research Link, Singapore, Singapore.
authors.forename: Paul
authors.initials: P
authors.lastname: Free
authors.affiliation: Institute of Integrative Biology, University of Liverpool, Liverpool, United Kingdom.
authors.forename: Raphaël
authors.initials: R
authors.lastname: Lévy
mesh_terms: D000595:Amino Acid Sequence; D002462:Cell Membrane / Q000187:drug effects* / Q000378:metabolism; D003600:Cytosol / Q000187:drug effects / Q000378:metabolism; D016503:Drug Delivery Systems / Q000379:methods; D004705:Endocytosis / Q000187:drug effects*; D011992:Endosomes / Q000187:drug effects / Q000378:metabolism; D006046:Gold / Q000737:chemistry / Q000494:pharmacology*; D006367:HeLa Cells; D006801:Humans; D046529:Microscopy, Electron, Transmission; D008969:Molecular Sequence Data; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D010455:Peptides / Q000494:pharmacology*; D054322:tat Gene Products, Human Immunodeficiency Virus / Q000494:pharmacology*
chemical_list: D010455:Peptides; D054322:tat Gene Products, Human Immunodeficiency Virus; D006046:Gold
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