Poster Presentation 21st International Conference on Biological Inorganic Chemistry 2025

Recent advancements in cancer therapy highlight the promising synergy between chemotherapy and immunotherapy.¹ Particularly intriguing is the induction of Immunogenic Cell Death (ICD) that can trigger the release of damage-associated molecular patterns (DAMPs) from dying cancer cells, activating the immune system to target and suppress distant or metastatic tumors, thereby providing long-term immune protection.²

Several metal complexes have been identified as effective ICD inducers, showing promising results in enhancing immune responses.³ However, previous studies have not compared ICD capabilities between different metallodrugs nor explored the potential of conjugating multiple metal complexes into a single prodrug to assess whether the combination could provide performance greater than the sum of their parts.

This study aims to address this gap by combining distinct metal complexes into a single prodrug, enhancing tumor localization and immunomodulatory activity. We successfully conjugated ICD inducers to an oxaliplatin Pt(IV) scaffold, incorporating axial ligands derived from a gold(I) complex (SS-1) and a ruthenium(II) compound (plecstatin-1). Bi- and tri-metal derivatives were synthesized, purified, and fully characterized. The mechanism of action was investigated, and in-vitro and in-vivo studies were conducted to assess their potential as ICD inducers.

Our results show that these multi-metal complexes exhibit enhanced tumor localization and immunomodulatory effects compared to individual components or their co-administration. The combination of metal complexes in a single prodrug offers a novel approach to improve the efficacy of cancer therapy by harnessing the dual power of chemotherapy and immune activation. These findings provide a promising platform for the development of next-generation cancer treatments with enhanced therapeutic potential.