UC San Diego

Nanotechnology is a cutting edge scientific area that is fundamentally changing the way we design and administer medicines and therapies to patients. One area in which nanomedicine can have a large impact is through immune modulation and “nano-immunoengineering”. The size and unique cell-particle interaction patterns enable nanoparticles to interact with the immune system in ways that can impact the immune system in radically new and efficacious ways. This dissertation focuses on demonstrating how cell membrane coating can be merged with nanoparticle design to facilitate immune modulation to improve a variety of pathological conditions. The rationale for cell membrane coating and the use of nanoparticles in immune modulation is discussed in the first chapter of the dissertation.

The second portion of the dissertation concentrates on developing cancer cell membrane-coated nanoparticles for anticancer vaccination. Using the membrane of cancer cells serves as an ideal and multivalent antigen source, while coating around the adjuvant-loaded nanoparticle core provide immune stimulation and a codelivery of both components to the lymphatic system. The third portion of the dissertation dives into the use of erythrocyte membrane-coated nanoparticles for antibacterial vaccination. Pore-forming toxins naturally embed into red blood cell membrane, and can be delivered in the nanoparticulate form to provide intact toxin antigens to the immune system. Formation of anti-toxin antibodies then protect from toxin damage and also provide antivirulence immunity against bacterial infections. Finally, the fourth section of this dissertation will focus on a novel “nanosponge” for immune thrombocytopenia purpura. Platelet membrane coated nanoparticles can specifically absorb anti-platelet antibodies, sparing immune destruction of real platelets and reducing disease symptoms.

This dissertation will serve as an example of applying rational design and engineering of cell membrane coating and nanoparticle synthesis and loading to enhance immune system intervention in a variety of internal and external pathological challenges. By harnessing these tools, cell membrane-coated nanoparticles can have a great impact in the field of immunotherapy, and have much potential to be expanded upon for new therapeutic and prophylactic modalities.