CBET-0709468 Hill The project goal is to develop and validate the use of chalcopyrite-based nanostructures to target intracellular delivery of small interfering RNAs (siRNAs). The NER team will exploit known signal sequences in designing peptides also linked to the nanostructure platform to specifically concentrate the cargomolecules, siRNAs, within specific sub-cellular compartments. Signal sequences will utilize known cellular transport mechanisms and pathways to target mRNA knock-down. The proposed project has four objectives: 1) Develop a range of novel, functionalizable, fluorescent semiconductor chalcopyrite clusters in the 1-2 nm size range. 2) Describe and quantify delivery of peptide-chalcopyrite nanocluster conjugates into cells. 3) Demonstrate gene knock-down by chalcopyrite nanocluster-conjugated siRNAs. 4) Demonstrate gene knock-down by peptide-targeted chalcopyrite nanocluster delivered siRNAs. Chalcopyrite nanoclusters will be designed and synthesized with characteristics that will provide targeted and potent delivery of siRNA cargo molecules.