Polymeric micro- and nanoparticles have been utilized in the treatment of various diseases, such as cancer and infectious disease, but there is a need for more effective delivery of these particles to their intended targets and enhanced interaction with their target cells. Biomaterial-based devices can have enhanced therapeutic function through biomimicry of naturally occurring structures. The goal of this thesis work was to engineer multiple particle parameters, including size, shape, protein presentation, surface fluidity, polymer structure, hydrophobicity, and targeting capability, to create novel biomimetic polymeric micro- and nanoparticle platforms for enhanced drug delivery and cancer immunotherapy. Immunoengineering is a particularly clinically relevant application for particle therapeutics due to the recent clinical success of cancer immunotherapy and the pervasive role of the immune system in human disease.
Chapter one outlines the guiding aims of this thesis. Chapter two provides background on biomimetic particle design, focusing on cell membrane coating, artificial antigen presenting cells, and biomaterials for gene delivery. Chapters three and four describe the engineering of biomimetic anisotropic red blood cell and platelet membrane-coated particles, respectively, for enhanced stealth drug delivery. In chapter five, I describe the use of anisotropic nanoscale artificial antigen presenting cells for treatment of melanoma. And finally, in chapter six, I detail my work developing novel bioreducible lipophilic poly(beta-amino ester) nanoparticles for targeted mRNA delivery to dendritic cells and their ultimate use as a therapeutic cancer vaccine. Overall, I have developed biomimetic polymeric particles that mimic red blood cells, platelets, antigen presenting cells, and viruses, by precise engineering and modulation of various particle characteristics in order to optimize biomimicry and therapeutic function. The modular off-the-shelf particle platforms developed here have been found to have enhanced efficacy for their respective therapeutic applications and show significant promise in treating a range of disease states
