| Título: | pH-triggered endosomal escape of pore-forming Listeriolysin O toxin-coated gold nanoparticles |
| Autores: | Plaza-GA, Ismael ; Manzaneda González, Vanesa ; Kisovec, Matic ; Almendro Vedia, Víctor ; Muñoz Úbeda, Mónica ; Anderluh, Gregor ; Guerrero Martínez, Andrés ; Natale, Paolo ; López-Montero, Iván |
| Tipo de documento: | texto impreso |
| Editorial: | BMC, 2019 |
| Dimensiones: | application/pdf |
| Nota general: |
cc_by info:eu-repo/semantics/openAccess |
| Idiomas: | |
| Palabras clave: | Estado = Publicado , Materia = Ciencias: Química: Física , Materia = Ciencias Biomédicas: Biología: Biotecnología , Tipo = Artículo |
| Resumen: |
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. |
| En línea: | https://eprints.ucm.es/id/eprint/60125/1/s12951-019-0543-6 |
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