Since the discovery of RNA interference (RNAi), by which the activity of specific genes can be efficiently suppressed, synthetic small interfering RNA (siRNA)-mediated RNAi has been of substantial interest for various disease treatments.[1] However, the safe and effective delivery of siRNA to target cells remains a major hurdle for its widespread clinical applications.[2] Due to its polyanionic and macromolecular characteristics, naked siRNA cannot readily cross the cell membrane, and thus requires specific delivery vehicles to facilitate its intracellular uptake and cytosolic delivery for bioactivity. These delivery vehicles are also expected to improve the pharmacological properties of siRNA by reducing its susceptibility to serum nucleases, renal filtration, and uptake by the mononuclear phagocyte system.