Researchers from NYU Abu Dhabi’s (NYUAD) chemistry program and colleagues from the University’s biology program have developed and studied the biological activity of five new, metal-organic hybrid knotted molecules, termed metal-organic trefoil knots (M-TKs). These molecules can effectively deliver metals to cancer cells, demonstrating the potential to act as a new category of anti-cancer agents.
In a study published in the journal Chemical Science, NYUAD Research Scientists Farah Benyettou and Thirumurugan Prakasam from the Trabolsi Research Group, led by Ali Trabolsi, NYUAD Associate Professor of Chemistry, report that these nanoscale, water-soluble M-TKs showed high potency in vitro against six cancer cell lines and in vivo in zebrafish embryos.
The M-TKs, generated by metal-templated self-assembly of a simple pair of chelating ligands, were well tolerated in vitro by non-cancer cells but were significantly more potent than cisplatin, a common chemotherapy medication, in both human cancer cells—including those that were cisplatin-resistant—and in zebrafish embryos. In cultured cells, M-TKs introduce reactive oxygen species (ROS) that damage the mitochondria of cancer cells, but not the nuclear DNA or the plasma membrane.
“The cytotoxicity and wide scope for structural variation of M-TKs indicate the potential of synthetic metal-organic knots as a new field of chemical space for pharmaceutical design and development,” Trabolsi said. “There is significant promise for developing new cancer therapies that can complement the existing chemotherapy options that are currently used to treat nearly half of all cancer patients undergoing chemotherapy.”