Research Projects

Conventional chemotherapy is a common treatment for cancer, but many chemotherapeutic drugs struggle with poor solubility, selective targeting between normal and cancer cells, lack of specificity to the target site, chemoresistance, and severe side effects. This proposal aims to develop metal-based anticancer agents using a novel class of heterobimetallic iridium(III)-platinum(IV) (Ir-Pt) conjugates to address these issues and combat drug-resistant cancer. The construct will integrate cancer-cell specific, organelle-targeted, (photo)chemotherapeutic, and cell-trackable agents in a single system. The octahedral Pt(IV) prodrug will be tethered to dichloroacetate (DCA), an anticancer agent, and a multifunctional Ir(III) complexes with organelle-targeting capabilities and anticancer and imaging properties. DCA can reverse the Warburg effect, a phenomenon observed in cancer cells by inhibiting a key enzyme in mitochondria and causing apoptosis. Cyclometalated Ir(III) complexes have been highly sought after for their excellent anticancer activity, imaging properties, mitochondria-targeting capabilities, and high photodynamic therapeutic (PDT) effect. The anticancer activity of the developed conjugates will be evaluated in various 2D monolayer cancer cells, including drug-resistant cells and 3D multicellular tumor spheroids. The cellular internalization, imaging capabilities, and cell death mechanism of the conjugates will also be studied. The photocytotoxicity activity of the Ir-Pt conjugates will be investigated to determine their PDT effect. This holistic approach represents a first-in-class example of targeted heterobimetallic Ir-Pt conjugates as anticancer theranostic agents.