The project proposes a novel delivery strategy to maximize in vivo delivery of small interfering RNA (siRNA) loaded nanocarriers to tumor tissue. Hybrid core-shell nanoparticles are envisioned, consisting of a siRNA loaded matrix core that is surrounded by a functionalized lipid bilayer. The resulting nanoparticles will be characterized in depth with regard to their physicochemical properties and intracellular siRNA delivery potential. In a next step, the designed nanoparticles will be anchored to the surface of tumoritropic cells in a reversible manner. In this way, following tumor infiltration of the carrier cells, siRNA loaded nanocarriers can be released in the microenvironment, enabling siRNA delivery of the neighboring tumor cells. The influence of the nanoparticle coupling strategy on the key functions of the carrier cell will be analyzed. The tumor accumulation of both nanoparticles and carrier cell will be visualized and quantified using non-invasive optical imaging. Finally, the ability of the nanoparticles to induce an RNAi effect in vivo will be evaluated in a tumor mouse model.