Abstract: The invention provides modified Transferrin (Tf) molecules and conjugates of the Tf molecules with a therapeutic agent. The invention also provides methods of treating cancer wherein the therapeutic agents are chemotherapeutic agents. The modified Tf molecules improve the delivery of the conjugated agent to a target tissue. In some embodiments, the modified Tf molecule has a mutation which decreases the release of bound iron from a Tf complex. The complex can also contain, for instance, a carbonate, oxalate, or other anion to stabilize the Tf iron complex.

Abstract: The present invention provides transferrin (Tf) conjugates of anti-cancer agents with increased cellular association and increased cellular internalization. The present invention also provides methods of treating cancer comprising administration of a Tf conjugate with increased cellular association to a subject with cancer. The present invention additionally provides methods of making, as well as screening for, Tf conjugates with increased cellular association or cellular internalization. The present invention also provides Tf conjugates with increased cellular association and internalization for delivering nucleic acids to cancer cells.