Insights into the Theranostic Activity of Nonoxido V^IV: Lysosome-Targeted Anticancer Metallodrugs

Developing new anticancer agents can be useful, with the ability to diagnose and treat cancer worldwide. Previously, we focused on examining the effects of nonoxidovanadium(IV) complexes on insulin mimetic and cytotoxicity activity. In this study, in addition to the cytotoxic activity, we evaluated their bioimaging properties. This study investigates the synthesis of four stable nonoxido V^IV complexes [V^IV(L^1-4)₂] (<b>1</b>-<b>4</b>) using aroylhydrazone ligands (H₂L^1-4) and their full characterization in solid state and the solution phase stability using various physicochemical techniques. The biomolecular (DNA/HSA) interaction of the complexes was evaluated by using conventional methods. The <i>in vitro</i> cytotoxicity of <b>1</b>-<b>4</b> was studied against A549 and LN-229 cancer cell lines and found that drug <b>2</b> displayed the highest activity among the four. Since <b>1</b>-<b>4</b> are fluorescently active, live cell imaging was used to evaluate their cellular localization activity. Complexes specifically target the lysosome and damage lysosome integrity by producing an excessive amount (9.7-fold) of reactive oxygen species (ROS) compared to the control, which may cause cell apoptosis. Overall, this study indicates that <b>2</b> has the greatest potential for the development of multifunctional theranostic agents that combine imaging capabilities and anticancer properties of nonoxidovanadium(IV)-based metallodrugs.