  In this manuscript, we propose a simple and versatile methodology to design
nanosystems based on biocompatible and multicomponent mesoporous silica
nanoparticles (MSNs) for infection management. This strategy relies on the
combination of antibiotic molecules and antimicrobial metal ions into the same
nanosystem, affording a significant improvement of the antibiofilm effect
compared to that of nanosystems carrying only one of these agents. The
multicomponent nanosystem is based on MSNs externally functionalized with a
polyamine dendrimer (MSN-G3) that favors internalization inside the bacteria
and allows the complexation of multiactive metal ions (MSN-G3-Mn+).
Importantly, the selection of both the antibiotic and the cation may be done
depending on clinical needs. Herein, levofloxacin and Zn2+ ion, chosen owing to
both its antimicrobial and osteogenic capability, have been incorporated. This
dual biological role of Zn2+ could have and adjuvant effect thought destroying
the biofilm in combination with the antibiotic as well as aid to the repair and
regeneration of lost bone tissue associated to osteolysis during infection
process. The versatility of the nanosystem has been demonstrated incorporating
Ag+ ions in a reference nanosystem. In vitro antimicrobial assays in planktonic
and biofilm state show a high antimicrobial efficacy due to the combined action
of levofloxacin and Zn2+, achieving an antimicrobial efficacy above 99%
compared to the MSNs containing only one of the microbicide agents. In vitro
cell cultures with MC3T3-E1 preosteoblasts reveal the osteogenic capability of
the nanosystem, showing a positive effect on osteoblastic differentiation while
preserving the cell viability.
