Abstract: Protein-based nanoparticles for treating cancer, such as those characterized by intracranial tumors, and methods of forming such protein-based nanoparticles via electrohydrodynamic jetting methods are provided. The nanoparticle may comprise a water-soluble protein having an average molecular weight of ?about 8 kDa and ?about 700 kDa. In certain variations, the water-soluble protein is cross-linked (e.g., with an optional crosslinking agent) and defines a mesh structure having an average linear mesh size of ?about 1 nm to ?about 4 nm. The nanoparticle may have a transcription factor such as a therapeutic nucleic acid in the mesh structure. Methods of making such nanoparticles may include jetting a liquid comprising the water-soluble protein through a nozzle, followed by exposing the liquid to an electric field sufficient to solidify the liquid and form the protein-based nanoparticles described above.