Plaza-GA, IsmaelManzaneda González, VanesaKisovec, MaticAlmendro Vedia, Víctor GalileoMuñoz Úbeda, MónicaAnderluh, GregorGuerrero Martínez, AndrésNatale, PaoloLópez-Montero, Iván2023-06-172023-06-1720191477-315510.1186/s12951-019-0543-6https://hdl.handle.net/20.500.14352/12302The 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)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.engAtribución 3.0 Españajournal articlehttps://doi.org/10.1186/s12951-019-0543-6open accessNanoparticlesLysosomal escapeListeriolysin O toxinQuantum dotsDrug deliveryFísica (Química)Biotecnología3399 Otras Especialidades Tecnológicas