Lay summary
Dendrimers are nano-size macromolecules possessing an overall spherical structure with radiating branching units and functional end groups on the surface. Because of these unique structural and functional properties, dendrimers provide an ideal platform to build nanoparticles that might be used as nanovectors for systemic delivery of complex therapeutic agents, like small interfering RNAs (siRNAs). In this project, we will develop biocompatible dendrimers modified with low molecular weight ligands or antibodies to achieve selective delivery of siRNA therapeutics to specifically targeted prostate cancer cells or HIV-infected cells. For this purpose, various dendrimer conjugates will be designed via computer-aided modeling and assembled via chemical synthesis. Their assembly into nanoparticles and interaction with siRNAs, their ability to protect siRNA from degradation, deliver siRNA into the targeted cells and produce the desired gene silencing effect will be investigated using HIV-infected human primary cells and prostate cancer cells. Further in vivo validation of the nanovector systems will be done using humanized HIV-infected mice and prostate tumor-xenografts in mice models to assess the antiviral and anticancer activity as well as toxicity. The goal of this project is to exploit the potential of dendrimers as effective nanovectors for targeted delivery of siRNA therapeutics by combining specific and complementary expertise in nanotechnology and biomedicine in the context of a transnational collaboration within Europe.