Post-formulation peptide drug loading of nanostructures for metered control of NF-κB signaling

Hua Pan, Olena Ivashyna, Bhaswati Sinha, Gregory M. Lanza, Lee Ratner, Paul H. Schlesinger, Samuel A. Wickline

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

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.

Original languageEnglish
Pages (from-to)231-238
Number of pages8
JournalBiomaterials
Volume32
Issue number1
DOIs
StatePublished - Jan 2011

Keywords

  • Drug delivery
  • Inflammation
  • Lipid
  • Membrane
  • Nanoparticle
  • Peptide

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