Postformulation peptide drug loading of nanostructures.

Cytolytic peptides have commanded attention for their anticancer potential because the membrane-disrupting function that produces cell death is less likely to be overcome by resistant mutations. Congruently, peptides that are involved in molecular recognition and biological activities become attractive therapeutic candidates because of their high specificity, better affinity, reduced immunogenicity, and reduced off target toxicity. However, problems of inadequate delivery, rapid deactivation in vivo, and poor bioavailability have limited clinical application.

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

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.

Lipid membrane editing with peptide cargo linkers in cells and synthetic nanostructures.

Current strategies for deploying synthetic nanocarriers involve the creation of agents that incorporate targeting ligands, imaging agents, and/or therapeutic drugs into particles as an integral part of the formulation process. Here we report the development of an amphipathic peptide linker that enables postformulation editing of payloads without the need for reformulation to achieve multiplexing capability for lipidic nanocarriers. To exemplify the flexibility of this peptide linker strategy, 3 applications were demonstrated: converting nontargeted nanoparticles into targeting vehicles; adding cargo to preformulated targeted nanoparticles for in vivo site-specific delivery; and labeling living cells for in vivo tracking.

Detergent-activated BAX protein is a monomer.

BAX is a pro-apoptotic member of the BCL-2 protein family. At the onset of apoptosis, monomeric, cytoplasmic BAX is activated and translocates to the outer mitochondrial membrane, where it forms an oligomeric pore. The chemical mechanism of BAX activation is controversial, and several in vitro and in vivo methods of its activation are known.