%0 Journal Article
%A John Jairo Aguilera-Correa
%A Yara Tasrini
%A Gisbert Garzarán, Miguel
%A Aude Boulay
%A Tamara Carvalho
%A Fabien P. Blanchet
%A Vallet Regí, María Dulce Nombre
%A Laurent Kremer
%T In vivo antimicrobial activity of engineered mesoporous silica nanoparticles targeting intracellular mycobacteria
%D 2025
%U https://hdl.handle.net/20.500.14352/135062
%X Treatments of Mycobacterium marinum, a common non-tuberculous mycobacterium associated with cutaneous infections are very challenging, emphasizing the development of new therapeutic approaches. Here we report the functionalization of mesoporous silica nanoparticles (MSN) with a series of triphenylphosphonium (TPP) substituents, which endowed them with affinity towards the surface of M. marinum in vitro, as well as within infected THP-1 cells. The presence of these nanoparticles at the bacterial surface prevents their uptake by human macrophages and dendritic cells. When loaded with doxycycline, the nanosystem exerts a potent anti-bacterial effect in planktonic cultures, biofilms, and in M. marinum-infected macrophages. Strikingly, in the M. marinum/zebrafish infection model, the doxycycline-loaded nanoparticles are associated with a pronounced decrease in the bacterial burden and a high embryo survival rate. These results disclose the proposed MSN nanosystems as a promising alternative for the treatment of M. marinum infection and, presumably, against a broader range of mycobacterial infections.
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