RT Journal Article
T1 pH-triggered endosomal escape of pore-forming Listeriolysin O toxin-coated gold nanoparticles
A1 Plaza-GA, Ismael
A1 Manzaneda González, Vanesa
A1 Kisovec, Matic
A1 Almendro Vedia, Víctor Galileo
A1 Muñoz Úbeda, Mónica
A1 Anderluh, Gregor
A1 Guerrero Martínez, Andrés
A1 Natale, Paolo
A1 López-Montero, Iván
AB 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.
PB BMC
SN 1477-3155
YR 2019
FD 2019
LK https://hdl.handle.net/20.500.14352/12302
UL https://hdl.handle.net/20.500.14352/12302
LA eng
NO The research leading to these results has received funding from the European Research Council under the European Union's Seventh Framework Programme (ERC grant agreement n° 338133)
NO Unión Europea. FP7
NO Ministerio de Ciencia e Innovación (MICINN)
NO Comunidad de Madrid
NO Universidad Complutense de Madrid
DS Docta Complutense
RD 7 oct 2024