The precise design strategies that achieve structural optimization of both metallodrugs and self-reported metallodrug carriers can overcome the major limitations of metallodrug development. Herein, we Show more
The precise design strategies that achieve structural optimization of both metallodrugs and self-reported metallodrug carriers can overcome the major limitations of metallodrug development. Herein, we structurally modified a conventional half-sandwich Ru(arene)(bipyridine) complex into a fluorogenic and esterase-responsive prodrug nanosystem via functionalizing the N,N'-bidentate bipyridine ligand with 10,12-pentacosadiynoic acid derivative, thereby designing an amphiphilic complex with the ability for coassembly. Prior to obtaining the nanoassembly, in an attempt to infer the benefits of functionalizing the ligand, a series of four organoruthenium complexes, including the amphiphilic complex, was prepared and characterized. The nanoassembly is found to release the Ru complex in the presence of porcine liver esterase concomitantly with a 4-fold increase in its fluorescence intensity. Such a stimuli-responsive behavior is exploited for real-time release monitoring of Ru complex and understanding its functionality to induce cell death in HeLa and THP-1 cancer cells. Compared to the free Ru complex, this nanosystem exhibits better cellular uptake and 100-fold higher cytotoxicity in HeLa cancer cells while being less toxic in noncancerous GM5756 cells. N-Acetylcysteine-induced GSH augmentation studies revealed that the nanoassembly exerts antiproliferative activity through oxidative stress. Toxicity analysis in zebrafish embryos confirmed the biocompatibility of the nanoformulations, suggesting a promising future in vivo studies. Show less
A novel strategy in metallodrug discovery today is incorporating clinically approved drugs into metal complexes as coordinating ligands. Using this strategy, various drugs have been repurposed to prep Show more
A novel strategy in metallodrug discovery today is incorporating clinically approved drugs into metal complexes as coordinating ligands. Using this strategy, various drugs have been repurposed to prepare organometallic complexes to overcome the resistance of drugs and to design promising alternatives to currently available metal-based drugs. Notably, the combination of organoruthenium moiety and clinical drug in a single molecule has been shown, in some instances, to enhance pharmacological activity and reduce toxicity in comparison to the parent drug. Thus, for the past two decades, there has been increasing interest in exploiting metal-drug synergism to develop multifunctional organoruthenium drug candidates. Herein, we summarized the recent reports of rationally designed half-sandwich Ru(arene) complexes containing different FDA-approved drugs. This review also focuses on the mode of coordination of drugs, ligand-exchange kinetics, mechanism of action, and structure-activity relationship of organoruthenated complexes containing drugs. We hope this discussion may serve to shed light on future developments in ruthenium-based metallopharmaceuticals. Show less