title: Post-formulation peptide drug loading of nanostructures for metered control of NF-κB signaling.
abstract: The NF-κB signaling pathway is an attractive therapeutic target for cancer and chronic inflammatory diseases. In this study, we report the first strategy to achieve NF-κB 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 peptide-nanoparticle complex is formed (dissociation constant ∼ 0.14 μM) and metered inhibition of both NF-κB signaling and 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.
authors.affiliation: Department of Medicine, Washington University School of Medicine, St Louis, MO 63110, USA.
authors.forename: Hua
authors.initials: H
authors.lastname: Pan
authors.forename: Olena
authors.initials: O
authors.lastname: Ivashyna
authors.forename: Bhaswati
authors.initials: B
authors.lastname: Sinha
authors.forename: Gregory M
authors.initials: GM
authors.lastname: Lanza
authors.forename: Lee
authors.initials: L
authors.lastname: Ratner
authors.forename: Paul H
authors.initials: PH
authors.lastname: Schlesinger
authors.forename: Samuel A
authors.initials: SA
authors.lastname: Wickline
mesh_terms: D000595:Amino Acid Sequence; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D005466:Fluorocarbons / Q000737:chemistry; D008051:Lipid Bilayers / Q000378:metabolism; D008954:Models, Biological; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D049329:Nanostructures / Q000737:chemistry* / Q000648:ultrastructure; D010455:Peptides / Q000737:chemistry / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D005466:Fluorocarbons; D008051:Lipid Bilayers; D016328:NF-kappa B; D010455:Peptides