RT Journal Article T1 Antibiotic delivery from bone-targeted mesoporous silica nanoparticles for the treatment of osteomyelitis caused by methicillin-resistant Staphylococcus aureus A1 Aguilera Correa, John Jairo A1 Gisbert Garzarán, Miguel A1 Mediero, A. A1 Pablo Velasco, David De A1 Fernández Aceñero, María Jesús A1 Lozano Borregón, Daniel A1 Esteban, J. A1 Vallet Regí, María Dulce Nombre AB Osteomyelitis is a hard-to-treat infection of the bone and bone marrow that is mainly caused by Staphylococcus aureus, with an increasing incidence of methicillin-resistant S. aureus (MRSA). Owing to the aggressiveness of these bacteria in colonizing and destroying the bone, systemic antibiotic treatments fail to eradicate the infection. Instead, it normally entails surgery to remove the dead or infected bone. In this work, we report bone-targeted mesoporous silica nanoparticles for the treatment of osteomyelitis. The nanoparticles have been engineered with a functional gelatine/colistin coating able to hamper premature release from the mesopores while effectively disaggregating the bacterial biofilm. Because antibiotic resistance is a global emergency, we have designed two sets of identical nanoparticles, carrying each of them a clinically relevant antibiotic, that have demonstrated to have synergistic effect. The bone-targeted nanoparticles have been thoroughly evaluated in vitro and in vivo, obtaining a notable reduction of the amount of bacteria in the bone in just 24 h after only one dose, and paving the way for localized, nanoparticle-mediated treatment of MRSA-caused osteomyelitis.Statement of significanceIn this work, we propose the use of bone-targeted mesoporous silica nanoparticles to address S. aureus-caused osteomyelitis that render synergistic therapeutic effect via multidrug delivery. Because the bacterial biofilm is responsible for an aggressive surgical approach and prolonged antibiotic treatment, the nanoparticles have been functionalized with a functional coating able to both disaggregate the biofilm, hamper premature antibiotic release and protect the intact bone. These engineered nanoparticles are able to effectively target bone tissue both in vitro and in vivo, showing high biocompatibility and elevated antibacterial effect. PB Elsevier SN 1742-7061 YR 2022 FD 2022-10-28 LK https://hdl.handle.net/20.500.14352/72580 UL https://hdl.handle.net/20.500.14352/72580 LA eng NO Aguilera Correa, J. J., Gisbert Garzarán, M., Mediero, A. et al. «Antibiotic Delivery from Bone-Targeted Mesoporous Silica Nanoparticles for the Treatment of Osteomyelitis Caused by Methicillin-Resistant Staphylococcus Aureus». Acta Biomaterialia, vol. 154, diciembre de 2022, pp. 608-25. DOI.org (Crossref), https://doi.org/10.1016/j.actbio.2022.10.039. NO CRUE-CSIC (Acuerdos Transformativos 2022)RESEARCHER ID S-2443-2016 (Miguel Gisbert Garzarán)ORCID 0000-0001-9815-0354 (Miguel Gisbert Garzarán)RESEARCH ID B-5081-2017  (Daniel Lozano Borregón)ORCID 0000-0001-5902-9201 (Daniel Lozano Borregón)RESEARCHER ID M-3378-2014 (María Vallet Regí)ORCID 0000-0002-6104-4889 (María Vallet Regí) NO Unión Europea NO Instituto de Salud Carlos III DS Docta Complutense RD 9 abr 2025