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

Area of Science:

• Inorganic chemistry
• Medicinal chemistry
• Cancer research

Background:

• Development of novel anticancer agents is crucial for global cancer management.
• Previous work focused on nonoxidovanadium(IV) complexes for insulin mimetic and cytotoxic activity.
• This study expands on evaluating bioimaging properties alongside cytotoxicity.

Purpose of the Study:

• To synthesize and characterize new nonoxidovanadium(IV) complexes using aroylhydrazone ligands.
• To evaluate their biomolecular interactions, in vitro cytotoxicity, and bioimaging capabilities.
• To identify potential multifunctional theranostic agents for cancer therapy.

Main Methods:

• Synthesis of four nonoxidovanadium(IV) complexes [VIV(L1-4)2] (1-4) with aroylhydrazone ligands.
• Physicochemical characterization and solution phase stability assessment.
• In vitro cytotoxicity assays against A549 and LN-229 cancer cell lines.
• Live cell imaging to determine cellular localization and reactive oxygen species (ROS) production.

Main Results:

• Complexes 1-4 were successfully synthesized and characterized.
• Complex 2 exhibited the highest in vitro cytotoxicity against tested cancer cell lines.
• The complexes demonstrated fluorescent activity and targeted lysosomes in live cells.
• Significant ROS production (9.7-fold increase) was observed, leading to lysosomal damage and potential apoptosis.

Conclusions:

• Nonoxidovanadium(IV) complexes, particularly complex 2, show promise as anticancer agents.
• The observed lysosomal targeting and ROS generation highlight a potential mechanism for inducing cancer cell apoptosis.
• Complex 2 has potential as a multifunctional theranostic agent, combining anticancer and bioimaging properties.