Biomimetic Nanoparticles for Targeted Delivery and Removal

Author(s): Dehaini, Diana | Advisor(s): Zhang, Liangfang | Abstract: Nanoparticle drug delivery has revolutionized the way we think of disease treatment over the last decade. The encapsulation of drugs into nanoparticles has led to better bioavailability, longer circulation times and an extended therapeutic window, and fewer off target effects than free drug administration. Nanoparticles are able to be tailored to specific applications through their size, shape, and surface design. Nanoparticles are just beginning to see clinical translation and FDA approval. Recently, significant efforts have been put into creating biomimetic targeting, particularly utilizing cell membrane coatings. Cell membrane can be used as a biomaterial to “cloak” nanoparticles, endowing them with the surface properties of the parent cell. Each different cell type in the body has a distinct surface structure with lipids, proteins, and receptors perfectly tailored to its purpose and location. Some of these proteins, such as CD47 or the selectins, have well known purposes like immune evasion or specific receptor targeting respectively. Additionally, there are yetundescribed and uncharacterized surface moieties on cells whose properties can be retained by using the entire cell membrane as a biomaterial. By cloaking nanoparticles in cell membrane, they retain many of the properties of the original cell type. We show that this allows for new biointerfacing abilities and a highly specific drug delivery vehicle. This new technology also promises future clinical translation,as the materials are inherently biocompatible. Herein, we will discuss engineered nanoparticle platforms that utilize this biomimetic cell membrane coating technology to improve the delivery of drugs, and additionally the detoxification and removal of pathogens. The biomimetic techniques developed during this PhD range from novel formulations of classical small molecule targeting for cancer therapy, to new methods of utilizing a fusion of natural cell membranes to create custom tailored targeting. These improvements to the field of targeted drug delivery will hopefully lead to better use of drugs and treatment of disease, and a higher level of tailoring ability available to engineers designing future platforms.