The facile synthesis of a novel bis-(guanidinium)-tetrakis-(beta-cyclodextrin) tetrapod, the first example of a new host family, was described, and the ability of the cyclodextrin CyD tetrapod to form molecular association with siRNA and DNA guest molecules was demonstrated. Affinity capillary electrophoresis was used to determine the binding constant with the evaluation of the shift in the electrophoretic mobility mu of injected siRNA when various CyD tetrapod concentrations were added to the run buffer. A significant association constant (K(a) =16,000 M(-1)) was obtained with borate buffer when double-stranded siRNA was primarily opened with the help of temperature. An efficient cellular transfection of siRNA into human embryonic lung fibroblasts was observed by fluorescence microscopy.