This invention provides compositions comprising at least one protein nanoparticle comprising a protein and a non-ionic surfactant. In certain embodiments, the nanoparticle further comprises a therapeutic agent, such as a siRNA. In other embodiments, the nanoparticle further comprises a cell surface receptor ligand. Also included in the invention are methods of preparing the compositions of the present invention, and methods of treating, ameliorating or preventing a disease or disorder in a subject in need thereof using the compositions of the present invention.