%0 Journal Article
%A Plaza-GA, Ismael
%A Manzaneda González, Vanesa
%A Kisovec, Matic
%A Almendro Vedia, Víctor Galileo
%A Muñoz Úbeda, Mónica
%A Anderluh, Gregor
%A Guerrero Martínez, Andrés
%A Natale, Paolo
%A López-Montero, Iván
%T pH-triggered endosomal escape of pore-forming Listeriolysin O toxin-coated gold nanoparticles
%D 2019
%@ 1477-3155
%U https://hdl.handle.net/20.500.14352/12302
%X Background: A major bottleneck in drug delivery is the breakdown and degradation of the delivery system through the endosomal/lysosomal network of the host cell, hampering the correct delivery of the drug of interest. In nature, the bacterial pathogen Listeria monocytogenes has developed a strategy to secrete Listeriolysin O (LLO) toxin as a tool to escape the eukaryotic lysosomal system upon infection, allowing it to grow and proliferate unharmed inside the host cell. Results: As a “proof of concept”, we present here the use of purifed His-LLO H311A mutant protein and its conjuga  tion on the surface of gold nanoparticles to promote the lysosomal escape of 40 nm-sized nanoparticles in mouse embryonic fbroblasts. Surface immobilization of LLO was achieved after specifc functionalization of the nanoparti  cles with nitrile acetic acid, enabling the specifc binding of histidine-tagged proteins. Conclusions: Endosomal acidifcation leads to release of the LLO protein from the nanoparticle surface and its self-assembly into a 300 Å pore that perforates the endosomal/lysosomal membrane, enabling the escape of nanoparticles.
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