Development of a Highly In Vivo Efficacious Dual Antitumor and Antiangiogenic Organoiridium Complex as a Potential Anti-Lung Cancer Agent.

While the phenomenal clinical success of blockbuster platinum (Pt) drugs is highly encouraging, the inherent and acquired resistance and dose-limiting side effects severely limit their clinical application. To find a better alternative with translational potential, we synthesized a library of six organo-Ir half-sandwich [(η-Cp)Ir(N∧N)Cl]-type complexes. screening identified two lead candidates [(η-Cp)Ir(PhPhen)Cl] (, Cp = tetramethyl-phenyl-cyclopentadienyl and PhPhen = 4,7-diphenyl-1,10-phenanthroline) and [(η-Cp)Ir(PhPhen)Cl] (, Cp = tetramethyl-biphenyl-cyclopentadienyl) with nanomolar IC values. Both and efficiently overcame Pt resistance and presented excellent cancer cell selectivity . Potent antiangiogenic properties of were demonstrated in the zebrafish model. Satisfyingly, and its nanoliposome presented considerably higher antitumor efficacy as compared to cisplatin, as well as earlier reported Ir half-sandwich complexes in mice bearing the A549 non-small lung cancer xenograft. In particular, complex is the first example of this class that exerted dual antiangiogenic and antitumor properties.