UC San Diego

Harmful reagents, including small molecules, proteins, bacteria, and viruses, have posed a serious threat to public health. The current medical countermeasures reply on accommodating the structures of the causative agents for the design of therapeutic agents. Despite their pivotal roles in treating numerous diseases, these strategies show inadequate efficacy, in part, due to the diversity of toxicants, leading to narrow-spectrum neutralization. Therefore, it is essential to explore innovative methods of biological neutralization that offer enhanced therapeutic efficacy. The dissertation focuses on the development of novel cell membrane-based nanostructures. Cell membraned based nanoparticles represent a unique solution by mimicking susceptible host cells, intercepting harmful agents without knowing their molecular structure. By functionalization of cell membrane coated nanoparticles and exploiting novel nanostructures, these nanoformulations have potential in broad spectrum neutralization of a variety of pathological agents.The first chapter discusses recent advances in biological neutralization using cell membrane coated nanoparticles, which explores different source cell membranes and functionalization strategies. The second chapter of this thesis introduces a new type of neuron cell membrane coated nanoparticles, highlighting its potential in neutralizing neurotoxins. Functioning as neuron decoys, these nanoparticles bind with neurotoxins, diverting them away from attacking the neurons. The third chapter of this thesis will concentrate on the functionalization of CNPs, including surface modification with heparin and ganglioside moieties via metabolic engineering. Heparin functionalized CNPs demonstrate the ability to bind with SARS-CoV-2, inhibiting viral infectivity. Glycan-modified CNPs enhance botulinum toxin binding capacity, which indicate higher detoxification efficacy than nanoparticles made from unmodified CNPs. Finally, the fourth chapter will demonstrate the design and biological neutralization of a new therapeutic platform, nanodiscs, a discoidal-shaped nanostructure. By inheriting native cell membrane functions, these nanodiscs have a broad neutralization ability against bacterial toxins and neurotoxins. The dissertation serves as a paradigm to design nanostructures with different attributes for biological neutralization. By incorporating varying cell membrane types and surface engineering strategies, the functionalities of cell membranes are significantly enhanced. Additionally, nano discs put forth a new strategy for neutralization, counteracting the obstacles related to toxin associated challenges. These cell membrane-based nanostructures broaden the current arsenals for biological neutralization