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pH-triggered endosomal escape of pore-forming Listeriolysin O toxin-coated gold nanoparticles

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Plaza-GA, Ismael and Manzaneda González, Vanesa and Kisovec, Matic and Almendro Vedia, Víctor and Muñoz Úbeda, Mónica and Anderluh, Gregor and Guerrero Martínez, Andrés and Natale, Paolo and López-Montero, Iván (2019) pH-triggered endosomal escape of pore-forming Listeriolysin O toxin-coated gold nanoparticles. Journal of Nanobiotechnology, 17 (1). ISSN 1477-3155

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Official URL: https://doi.org/10.1186/s12951-019-0543-6



Abstract

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.


Item Type:Article
Additional Information:

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)

Uncontrolled Keywords:Nanoparticles, Lysosomal escape, Listeriolysin O toxin, Quantum dots, Drug delivery
Subjects:Sciences > Chemistry > Physics
Medical sciences > Biology > Biotechnology
ID Code:60125
Deposited On:22 Apr 2020 17:54
Last Modified:22 Apr 2020 17:54

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