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Nanjing University, China
Molecular Design of Metal Complexes for Tumor Targeting
Selective targeting and activation offer the possibility to overcome the side effects and toxicities of clinical anticancer platinum drugs. In this talk, I will summarize some recent approaches to design platinum and copper complexes with targeting properties.
Osteosarcoma is responsible for considerable deaths of children and adolescents worldwide. Standard treatments for osteosarcoma include surgery and neo-adjuvant and adjuvant chemotherapy, and platinum-based anticancer agents such as cisplatin are a mainstay in the clinic. However, systemic toxicities, such as neurotoxicity, ototoxicity, and nephrotoxicity, are major barriers for achieving ideal efficacy of platinum drugs. Bisphosphonates are the most commonly prescribed pharmaceuticals and play a crucial role in bone-related diseases. We have designed a series of Pt(II)-bisphosphonate complexes which demonstrated bone-targeting ability and unique activities against osteosarcoma cell lines. Molecular mechanism of action of these complexes have been investigated.
Tumor metastasis and angiogenesis are the major obstacles in anticancer therapy. Copper complexes are potential anticancer drugs by virtue of their available redox properties and low toxicity. Aiming to overcome these challenges, we have designed lipophilic copper complexes with mitochondrion-targeting ability and potent anti-metastatic and anti-angiogenic activities. These examples demonstrate the versatility of copper(II) complexes for cancer therapy through multiple pathways.