Synthesis and aptamer-targeted nanoparticle delivery of ruthenium(III) theranostics

Two novel fluorescent analog of the Ru(III) compound, NAMI, were synthesized and characterized. Chapter 2 explored the effects of functionalization using lipophilic trifluoromethyl groups. This significantly increased the lipophilicity, cellular uptake, and in-vitro activity of the ruthenium complex, suggesting its potential as a potent anticancer agent. Aqueous ligand-exchange behaviour of the ruthenium complexes determined that the dissociation of a chloride ligand is favored to form active mono-aquo species. In chapter 3, nanoencapsulation of the NAMI analogs in aptamer-functionalized PLGA-PEG nanoparticles, showed promising results in enhancing drug transport into cells. The drug release behaviour of the nanoparticles revealed the existence of a burst-release phase, followed by a gradual and sustained leaching of drugs out of the nanoparticles. Despite achieving negligible cytotoxicity with nanoencapsulation, higher intracellular ruthenium content was observed. This work highlights the potential of nanoencapsulation strategies for improving the efficacy of ruthenium-based chemotherapeutics.