Methods and compositions for tracking or monitoring uptake of siRNA by mammalian cells are provided. The methods and compositions may be used to monitoring the silencing activity of the internalized siRNA. The compositions contain an siRNA, an optically or magnetically detectable nanoparticle such as a quantum dot and, optionally, a transfection reagent. Cells are contacted with an siRNA and an optically or magnetically detectable nanoparticle, optionally in the presence of a transfection reagent. Detection of internalized nanoparticles is indicative of siRNA uptake. The invention allows analysis, identification, processing, etc., of cells that have efficiently taken up siRNA. In one embodiment, cells are sorted into at least two populations based on the amount of siRNA taken up.