Small interfering RNA (siRNA) has a great potential in human disease treatment and life science research. But its delivery to cells is one of the most significant barriers to a successful application. Hence, new and optimized strategies for highly efficient siRNA delivery are urgently needed. However, a systematic optimization is hard to follow up because most siRNA-formulations are heterogeneous due to the existence of different particle sub-species. Consequently, it is not clear which species is responsible for the overall effect. We propose that gold nanoparticles that are coated with siRNA in a layer-by-layer approach (LbL-coated AuNPs) are excellent to overcome this limitation due to their high uniformity. In addition, the straightforward tailoring of their physicochemical properties makes them a favorable tool to identify parameters for highly efficient siRNA delivery. To follow up this approach we will focus on 1.) the fabrication LbL-coated AuNPs with a spatially defined release of siRNA inside cells, 2.) the correlation between physicochemical properties of LbL-coated AuNPs, the adsorption of proteins on their surface, the pathway of cellular uptake and silencing efficacy, 3.) the synthesis of fluorescently-labeled siRNA probes that allow for the discrimination between active and inactive siRNA inside cells. This project is only possible due to the collaboration of scientists from the field of Pharmaceutical Technology who bring their expertise in siRNAformulations and Organic Chemistry who have a profound knowledge in sophisticated fluorescent nucleic acid probes.
