Amphiphile-Assisted Synthesis of Ruthenium Nanoparticles for Controlled Release and Enhanced Antibacterial Activity

A novel procedure for preparing Ruthenium nanoparticles (RuNPs) based on low-molecular-weight amphiphilic molecules and Ru(III) complexes as antibacterial agents with controlled release properties has been developed. Two hydrophobic Ru(III) complexes, Ru-TOA and Ru-Benza, analogs to the NAMI-A prodrug, are encapsulated within the core of the micelles formed through the self-assembly of these amphiphiles. The self-assembly of amphiphile I, which contains a double polar head, results in highly water-stable and monodispersed RuNPs incorporating both hydrophobic Ru complexes. These RuNPs exhibit hydrodynamic sizes ranging from 26.7 to 104.2 nm for NPs derived from Ru-TOA complex, and ≈10 nm for those derived from Ru-Benza. Compared to Ru(III) complexes, these RuNPs offer several advantages, including protection from aqueous degradation and enhanced bacterial uptake. Moreover, post-synthesis modification of the RuNPs with molecular staples based on polyethylene glycol chains of varying lengths enables controlled Ru release, reducing the burst effect. Interestingly, these RuNPs demonstrate excellent antibacterial activity, with minimum inhibitory concentration (MIC) values of 16 mg·L^-1 and minimum bactericidal concentration (MBC) values of 32 mg·L^-1 against a broad range of Gram-positive bacteria, including S. aureus, Staphylococus pseudintermedius, and Enterococcus faecalis, highlighting their potential efficacy against clinically relevant bacterial strains.