Cytosolic Delivery of Peptide Inhibitors of Protein-Protein Interactions

Peptide inhibitors of the SPSB-iNOS interaction hold promise as novel, host-directed anti-infective compounds. These peptides act on the human innate immune system by enhancing the ability of macrophage cells to fight pathogens. This thesis explores the intracellular delivery of SPSB-iNOS inhibitors to macrophages using multiple drug delivery strategies. We uncovered the mechanistic basis for the uptake of cell-penetrating peptides, developed a basis for future research on nanoparticle-based delivery approaches, and ultimately were successful in delivering a meaningful amount of several peptide inhibitors into the cytosol.