The present invention is directed to protocells for specific targeting of hepatocellular and other
cancer cells which comprise a
nanoporous silica core with a supported
lipid bilayer; at least one agent which facilitates
cancer cell death (such as a traditional
small molecule, a macromolecular cargo (e.g. siRNA or a
protein toxin such as
ricin toxin A-chain or
diphtheria toxin A-chain) and / or a
histone-packaged
plasmid DNA disposed within the
nanoporous silica core (preferably supercoiled in order to more efficiently
package the
DNA into protocells) which is optionally modified with a
nuclear localization sequence to assist in localizing protocells within the
nucleus of the
cancer cell and the ability to express peptides involved in therapy (
apoptosis /
cell death) of the
cancer cell or as a reporter, a targeting
peptide which targets cancer cells in tissue to be treated such that binding of the protocell to the targeted cells is specific and enhanced and a
fusogenic peptide that promotes endosomal escape of protocells and encapsulated
DNA. Protocells according to the present invention may be used to treat cancer, especially including hepatocellular (liver) cancer using novel binding peptides (c-MET peptides) which selectively bind to hepatocellular tissue or to function in diagnosis of cancer, including
cancer treatment and
drug discovery.