In the last decade, N-heterocyclic carbene (NHC ) gold (I) complexes have emerged as a new generation of potential anticancer agents due to their impressively high cytotoxicity and stability. NHC-Au complexes induce cell apoptosis by targeting mitochondrial-related cellular pathways. Though these gold-based metallodrugs inhibit the growth of tumor cells, they also interact with human normal cells, a characteristic common for metal-based drugs, thus limiting their potential as cancer therapeutics. Cell-selectivity is an obvious area in need of improvement.<br/>This work describes a strategy to target cancer cells efficiently while potentially reducing metal-based side effects. The strategy involves covalently binding a cytotoxic NHC-Au(I) complex to a DNA aptamer. Aptamers are short single-stranded oligonucleotides, which are biocompatible, stable and more importantly, they are able to specifically recognize and effectively bind to their targets—in this case—cancer cells. As a model, we describes the synthesis and characterization of novel N-heterocyclic carbene (NHC) gold(I) complexes and their bio-conjugation to the CCRF-CEM leukemia specific aptamer sgc8c. Confirmation of successful bio-conjugation was achieved by using fluorescent tags on both the NHC-Au(I) complex and the aptamer. Cell viability assays indicate the NHC-Au(I)-aptamer conjugate <b>sgc8c-1</b> is more cytotoxic than the NHC-gold complex alone. A combination of flow cytometry, confocal microscopy, and cell viability assays provide clear evidence that the NHC-Au(I)-aptamer conjugate is selective for targeted CCRF-CEM leukemia cells.

N-Heterocyclic carbene gold(I) complexes conjugated to DNA-aptamers for targeted drug delivery

253rd National Meeting (2017)

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