Antibiotic delivery from bone-targeted mesoporous silica nanoparticles for the treatment of osteomyelitis caused by methicillin-resistant Staphylococcus aureus

Osteomyelitis is a hard-to-treat infection of the bone and bone marrow that is mainly caused by Staphy-lococcus aureus, with an increasing incidence of methicillin-resistant S. aureus (MRSA). Owing to the ag-gressiveness 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 pre-mature release from the mesopores while effectively disaggregating the bacterial biofilm. Because an-tibiotic 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 significance In 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 bac-terial 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 an-tibacterial effect. (c) 2022 The Author(s). Published by Elsevier Ltd on behalf of Acta Materialia Inc. This is an open access article under the CC BY license ( http://creativecommons.org/licenses/by/4.0/ )