Post‐formulation of peptide‐nanostructures for metered control of NF‐kB signaling

The NF‐kB signaling pathway is an attractive therapeutic target for cancer and chronic inflammatory diseases. In this study, we report the first strategy to achieve NF‐kB inhibition with a peptide inhibitor loaded into perfluorocarbon nanoparticles with the use of a simple post‐formulation mixing approach that utilizes an amphipathic cationic fusion peptide linker strategy for cargo insertion. A stable peptidenanoparticle complex is formed (dissociation constant of 0.14 mM) and metered inhibition of NF‐kB signaling and its downstream gene expression (ICAM‐1) is demonstrated in leukemia/lymphoma cells. This post‐formulation cargo loading strategy enables the use of a generic synthetic or biologic lipidic nanostructure for drug conjugation that permits flexible specification of types and doses of peptides and/or other materials as diagnostic or therapeutic agents for metered incorporation and cellular delivery.