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Cytosolic Diffusion and Peptide-Assisted Nuclear Shuttling of Peptide-Substituted Circa 102 Gold Atom Nanoclusters in Living Cells
journal contribution
posted on 2018-07-26, 00:00 authored by Dominique Desplancq, Nadja Groysbeck, Manuela Chiper, Etienne Weiss, Benoit Frisch, Jean-Marc Strub, Sarah Cianferani, Spyridon Zafeiratos, Eric Moeglin, Xavier Holy, Anne Laure Favier, Sacha De Carlo, Patrick Schultz, Danièle Spehner, Guy ZuberFor biological and
medical applications, a definable nanomaterial
and knowledge on its fate after administration are highly recommended
if not mandatory. Here, we synthesized a water-soluble gold nanocluster
by sodium borohydride reduction of chloroauric acid in the presence
of 5,5′-dithio-bis(2-nitrobenzoic acid). The resulting gold
nanocluster displayed the physical characteristics of a cluster containing
an inner core of about 100 gold atoms that was surrounded by an organic
monolayer made of about 30 thioaminobenzoic acids (TAB) and 14 anionic
thionitrobenzoic acids (TNB). The mixed TAB-,TNB-protected gold nanocluster
reacted well in water with thiolated peptides containing a nuclear
localization signal (NLS) or a nuclear export signal (NES) mainly
by exchange of the TNB, providing gold nanoclusters equipped with
8–9 intracellular active peptides and a remaining ligand coverage
consisting mostly of the zwitterion TAB. The behavior of these peptide–gold
nanoclusters inside the cytosol and nucleus of cells was then assayed
using an electroporation procedure allowing transient plasma membrane
permeability. Light and electron microscopy observations demonstrated
a consistent inflow and diffusion of the gold nanoclusters into the
cytosol. Inside the living cells, the distribution of the gold nanoparticles
was specifically driven by the appended signal peptides in a manner
similar to the distribution of NLS and NES-bearing proteins, demonstrating
diffusion ability, stability, and usage of these definable ligand-substituted
gold nanoclusters for intracellular applications.
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TABsodium borohydride reductionpeptideligand-substituted gold nanoclusters30 thioaminobenzoic acidssignalgold nanoclusters100 gold atomsNLSPeptide-Assisted Nuclear ShuttlingNESplasma membrane permeabilitygold nanoclusterelectron microscopy observationsPeptide-Substituted Circa 102 Gold Atom NanoclustersTNB
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