Cell Membrane-Coated Nanoparticles: Bridging Natural and Synthetic Nanomaterials for Novel Therapeutics

The advent of nanomedicine has had a tremendous impact on patient outcomes in the clinic. At the nanoscale, drug-loaded particles exhibit unique attributes that allow them to be more efficacious compared to free drug formulations, leading to better standard of care as well as increased patient compliance. Since the approval of Doxil, a liposomal formulation of the chemotherapy drug doxorubicin, two decades ago, researchers have been focused on leveraging nanotechnology to solve many of the hurdles in modern medicine. Despite the tremendous progress that has been made on this front, there is still much room for improvement. One major challenge in nanomedicine exists at the interface between synthetic nanomaterials and natural biological systems. My work has focused on a novel strategy for addressing the challenge of effective biointerfacing. This involves using natural membrane derived from the surface of cells to camouflage synthetic nanomaterials for the design of more effective and novel therapeutic modalities.;The first portion of this thesis will focus on the design of long-circulating drug delivery carriers by using a red blood cell membrane cloaking strategy to prolong systemic half-life. Building upon an initially reported red blood cell membrane-coated nanoparticle platform, drug-loaded nanocarriers are designed that can be actively targeted to tumors. Not only does natural membrane cloaking enable prolonged circulation for more effective drug delivery, but the presence of the natural membrane coating also facilitates the development of entirely new therapeutic modalities. The second part of this thesis will focus on the use of membrane-coated nanoparticles for the clearance of pathologic moieties. This is demonstrated for both pore-forming toxins that are secreted by bacteria and autoimmune antibodies targeting red blood cells. The final part of this thesis will outline the use of membrane-coated particles for specifically modulating the immune system. The concept is demonstrated for vaccination against both pathogen-derived toxins as well as against autologous cancer cells. Ultimately, the cell membrane-coated nanoparticle platform has the potential to greatly change the landscape of nanomedicine. From more effective drug delivery carriers to novel applications that have yet to be discovered, there are many avenues still waiting to be fully explored.