Engineering delivery systems for the treatment of Non-Hodgkin lymphoma

Hematological cancers, including various leukemias and lymphomas, are among the top 10 cancers diagnosed in people. The leukemia and lymphoma society estimates that there are nearly 1.7 million people in the United States living with or in remission from hematological cancers. The frontline therapeutics for these diseases usually consist of conventional chemotherapeutics, such as RCHOP (i.e., Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, and Prednisolone), a commonly used therapeutic regimen for many Non-Hodgkin lymphomas. While therapeutic remission can occur in 50 percent - 80 percent of these patients, nearly half are expected to develop relapsing or refractory disease. There exists a clear clinical need to generate targeted therapeutics that avoid undesirable side effects as well as can sufficiently address primary cancer to prevent follow-on disease. To address this issue, peptides have emerged in recent years as a novel improvement in cancer treatment, however, these drugs are limited by their poor cell penetration and serum instability. Lipidation of peptides, producing peptide amphiphiles, has been shown to allow for hydrophobically-driven self-assembly into peptide amphiphile micelles. There are many advantages to employing peptide amphiphile micelles as drug delivery devices, including improved serum stability, higher local therapeutic concentration, and co-loading of other materials, such as chemotherapeutic drugs or multiple PAs. In this dissertation, materials will be presented that utilize the peptide amphiphile micelle platform for the treatment of cancer along with the optimization of targeting elements that may be used to improve their drug delivery capacity. First to be discussed is the delivery of a novel, cytotoxic peptide (i.e., POSH(3.3A)-Tat) by micelle for the treatment of Non- Hodgkin lymphoma and multiple myeloma. This will be followed by foundational work focused on the targeting of Non-Hodgkin lymphoma using aptamers. Finally, a complement to aptamers in the antibody-mediated targeting of peptide amphiphile micelles will be covered.