Peptides have enormous potential as therapeutic agents due to their ease of rational design and target specificity, but they are limited by low stability and their ability to reach their desired target. This work demonstrates that a membrane destabilizing peptide linked to a hydrophobic domain self-assembles and disrupts the outer membrane of cancer cells in vitro. The peptide amphiphile can be coassembled with PEG-lipids into small spherical micelles 11 nm in diameter. The PEG chain shields the peptide amphiphile upon incubation with cells in vitro. Overtime, the micelles dissociate and the peptide amphiphile is internalized. It then localizes to the mitochondria and induces apoptosis. The method put forward in this work, the conjugation of a hydrophobic tail and subsequent incorporation into micelles with PEG-lipids, could be used as a general method to protect and deliver a wide variety of peptide therapeutics.

Peptides are also capable of stimulating an immune response but are generally weak immunogens on their own and require strong adjuvants to be effective, prohibiting their use in clinical applications. Peptide amphiphiles concentrate peptide antigens into self-assembled micelles and can increase uptake by immune cells. In this work, a peptide from the model antigen ovalbumin is linked to a lipid-like tail and is shown to self-assemble into cylindrical micelles. The micelles induce a higher cytotoxic T-cell response in mice compared to the peptide delivered in a standard adjuvant -- incomplete Freund's adjuvant (IFA). This work also investigates B-cell epitopes and shows that assembly into cylindrical micelles stabilizes the secondary structure of peptide antigens more than small spherical micelles do. To improve the immune response to both cytotoxic T-cell epitopes and B-cell epitopes, toll-like receptor agonists were incorporated into peptide amphiphile micelles without significantly changing the structure of the micelles. This indicates that peptide amphiphile micelles can provide a versatile platform for the development of modular, multivalent peptide-based vaccines.