1. pH-triggered endosomal escape of pore-forming Listeriolysin O toxin-coated gold nanoparticles.
- Author
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Plaza-Ga I, Manzaneda-González V, Kisovec M, Almendro-Vedia V, Muñoz-Úbeda M, Anderluh G, Guerrero-Martínez A, Natale P, and López Montero I
- Subjects
- Animals, Cell Line, Fibroblasts metabolism, Hydrogen-Ion Concentration, Listeria monocytogenes metabolism, Lysosomes metabolism, Mice, Models, Molecular, Bacterial Toxins metabolism, Drug Carriers metabolism, Endosomes metabolism, Gold metabolism, Heat-Shock Proteins metabolism, Hemolysin Proteins metabolism, Nanoparticles metabolism
- 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 purified His-LLO H311A mutant protein and its conjugation on the surface of gold nanoparticles to promote the lysosomal escape of 40 nm-sized nanoparticles in mouse embryonic fibroblasts. Surface immobilization of LLO was achieved after specific functionalization of the nanoparticles with nitrile acetic acid, enabling the specific binding of histidine-tagged proteins., Conclusions: Endosomal acidification 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.
- Published
- 2019
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