UC San Diego

Nanomedicine is a flourishing scientific field involving the design and control of matter on the nanometer scale for therapeutic use. One emerging avenue within the nanomedicine field is biodetoxification-based therapy, in which nano-sized structures are used to capture and retain biotoxins that would otherwise attack host cells, cause cellular damage, and trigger damage-associated signaling pathways to propagate diseases. Particularly, inflammation is a biological process that involves complex signaling networks and disease-specific cellular responses, posing significant challenge for designing medicine with high specificity and potency. To this end, the design flexibility of nanoparticle size and surface modification, and unique particle-cell interaction at the nanoscale can lead to novel and efficacious routes for anti-inflammatory therapy. Herein, we discuss the new generations of cell membrane-coated nanoparticles specifically tailored for biodetoxification-based anti-inflammatory therapy. Firstly, recent advances in neutralizing inflammatory cytokine will be discussed. The second portion of this dissertation will present neutrophil membrane-coated nanoparticle (neutrophil-NP) for therapeutic treatment of inflammatory arthritis. Neutrophil-NPs targeted and penetrated into the inflamed tissue, and effectively neutralized inflammatory cytokines. The third portion will cover the development of macrophage membrane-coated nanoparticle for neutralization of bacterial endotoxin and inflammatory cytokines, and management of bacterial sepsis. Finally, we will focus on the design of a unique ‘lure and kill’ nanoparticle for effective inhibition of phospholipase A2 (PLA2). The cell membrane works synergistically with a PLA2 attractant to ‘lure’ PLA2 for attack, then the PLA2 inhibitor in the cell membrane further ‘kills’ the enzyme. With effective inhibition of venomous PLA2, these nanoparticles further demonstrated strong inhibitory activity against PLA2 and attenuation of the inflammatory cascade during acute pancreatitis progression. This dissertation will serve as a paradigm for rational design of cell membrane-coated nanoparticles for therapeutic treatment of inflammatory disorders. By tapping into the biological challenges associated with anti-inflammatory therapy, cell membrane-coated nanoparticles can be tailored towards its designated biological target. By harnessing the design flexibility, this nanotechnology holds great potential to be developed into a class of drug-free anti-inflammatory nanomedicine that will be extraordinarily valuable for biomedical researchers and clinicians alike.