Unleashing the antibacterial and antibiofilm potential of silica-based nanomaterials functionalized with an organotin(<sc>iv</sc>) compound

Bacterial diseases caused by superbugs are expected to be the main cause of death worldwide within a decade as a consequence of the resistance they are acquiring to the antibiotics currently in use, therefore, the field of new antibacterial treatments is currently being thoroughly studied. The present work focuses on the synthesis, functionalization, characterization and antibacterial behaviour of different systems based on three different silica-based nanostructured materials (MSN, mesoporous silica nanoparticles, SBA-15 Santa Barbara amorphous-15 and FSP fibrous slica nanoparticles) which serve as scaffolds for the support of different platforms to target and treat bacterial diseases and biofilm formation. Thus, (3-carboxypropyl)triphenylphosphonium bromide (PPh3+) and a cytotoxic organotin(IV) fragment (Sn) have been incorporated in the silica-based materials to study their potential activity in different antibacterial applications. After a complete characterization of the synthesized systems, which confirmed the incorporation of both the targeting and the therapeutic fragments within the nanostructured materials, the antibacterial study of the materials demonstrated bactericidal capacity against Escherichia coli and perturbation of the bacteria metabolism via oxidative stress through an enhanced ROS (reactive oxygen species) production. In addition, biofilm inhibition and eradication tests of bacterial strains were carried out, showing that the activity of the materials in both biofilm inhibition and eradication is dependent on the concentration of the material. Furthemore, the material MSN-AP(1:1)-PPh3+-Sn containing the targeting triphenylphosphonium and a "SnPh3" fragment is capable of inhibiting and eradicating up to 50% of the formation of biofilms, which is outstanding for metallodrug-functionalized silica-based systems compared with other materials based on metal nanoparticles supported on silica. Finally, a hemolysis study was carried out with the nanostructured systems proving to be non-toxic, making them adequate for their subsequent use in preclinical trials through in vivo models.