UC San Diego

Drug delivery field has benefitted greatly from the advancements in nanoparticle technology. Nanoparticles have been developed to protect the payload, improve targeted delivery, control the release profile, and enhance solubility and bioavailability of drugs. In recent years, cell membrane-coated nanoparticle technology which is a biomimetic platform that utilizes cell membranes has revolutionized the drug delivery field by utilizing the natural characteristics and advantages cell membranes inherently possess. In order to further improve upon the cell membrane-coated nanoparticle technology, genetic engineering can be applied to the membranes thus granting the resulting nanoparticles with enhanced abilities depending on the type of proteins that are being engineered. In this dissertation, the ways in which genetic engineering can enhance the drug delivery capability of cell membrane-coated nanoparticle will be discussed. Herein, the first chapter will discuss the development and the current status of the biomimetic delivery strategies. The following two chapters will discuss the strategies using genetic engineering that can enhance two key aspects of drug delivery: cytosolic delivery and targeted delivery. The second chapter will focus on endosome escaping nanoparticles that enhance the cytosolic delivery of mRNA. The nanoparticle coated with membrane that was genetically engineered to mimic the influenza virus, once taken up by a host cell, is able to escape endosome and deliver mRNA to the cytosol which then can be translated into proteins. Model mRNA was successfully delivered to the cytosol using this platform when injected locally or systemically in a mouse model. The third chapter will focus on nanoparticles coated with membrane that was genetically engineered to target inflammation. The inflammation targeting nanoparticles, when loaded with an anti-inflammatory drug, was able to target and treat lung inflammation in a mouse model. This dissertation aims to demonstrate the versatility of the genetically engineered cell membrane-coated nanoparticle technology that can be applied to many facets of drug delivery. Customizability of its synthetic core, payload, membrane source and engineered membrane protein will allow this platform to suit the needs of vastly different application.