Organotin(IV) Azo Hydrazonates as Lysosome-Targeted Imaging and Anticancer Agents

Metallodrugs with organotin(IV) compounds emerging as a potential alternative to platinum-based drugs have revolutionized the field of both diagnosis and therapy, offering enhanced anticancer efficacy and bio-imaging capabilities for targeting intracellular organelles. In this regard, we embarked on an effort to explore the theranostic potential of a new class of azo hydrazone-based organotin(IV) complexes [Sn^IVL^1-4(Ph)₂] (1-4). The speciation studies suggested the complexes possess exceptional hydrolytic stability. Moreover, the hydrophobic nature of complexes, as determined through partition coefficient measurements, allows their efficient cellular penetration. The cytotoxic potential of 1-4 was evaluated against A549, HT-29, and NIH-3T3 cell lines, revealing that 3 was the most toxic among the series, with an IC₅₀ of 7.8 ± 0.2 µM against A549. Further in-depth mechanistic studies revealed that they preferentially accumulate in the lysosome, damage lysosomal membrane potential, and upregulate intracellular reactive oxygen species (ROS), leading to apoptotic-mediated cancer cell death.