Biomimetic Polymeric Particles for Biomedical Therapeutics

The overall goal of this thesis is to investigate the various applications in which micron and nanometer sized polymeric particles could be synthesized to mimic biological cells and tissues to achieve a therapeutic effect. Particularly, the emphasis of this particle design is on the development of artificial antigen presenting cells (aAPC) for immunotherapy. Although the work in this thesis is varied in nature, this dissertation can be broadly categorized in three aims. In Aim 1, the role of shape in the design of aAPC was investigated with respect to use for cancer immunotherapy. An automated process was developed for the generation of anisotropic particles as well as a model system with which to evaluate their therapeutic efficacy in combination with immune checkpoint blockades. These therapeutics were then evaluated in a murine model and non-spherical aAPC were found to outperform spherical aAPC. Furthermore, the core polymeric material was modified to generate much stronger aAPC, with sufficient immunostimulation to engage the endogenous immune cells. In Aim 2, the role of surface chemistry was investigated in the design and use of particles for biomimetic drug delivery applications. Particles with biomimetic surface bound lipid membranes were synthesized to mimic the natural biological membrane of a cell. Anisotropic particles were synthesized and coated with naturally derived red blood cell membranes and were found to outperform equivalently coated spherical nanoparticles in various important drug delivery parameters such as pharmacokinetics and cellular uptake and elimination. In Aim 3, the role of stimulus response was investigated with respect to particle design. Particles with thermally triggered shape memory effect were synthesized and found to allow for spatiotemporally controlled shape control of spherical and ellipsoidal particles. In addition, focused ultrasound triggered drug delivery particles were synthesized to enable focal, noninvasive neuromodulation in a rat seizure model. The particle therapeutic systems developed as part of this thesis will have a wide and diverse impact on multiple fields in medicine including immunotherapy, regenerative medicine, and neuromodulation