| Abstract: | 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. |