Neutrophil-Specific Drug Delivery as a Novel Mode for Colitis Immunotherapy

Ulcerative colitis is an inflammatory disorder of the colon. It is characterized by alternating periods of exacerbation or remission. Patients suffer from multiple symptoms such as rectal bleeding, diarrhea, and abdominal pain that can lead to hospitalization. In the most severe cases, surgery is inevitable. The causes of the disease remain unclear, however, factors such as diet, medications and stress that can modify the intestinal microbiome favor the development of the disease. In addition, several studies show that the neutrophils contribute to the progression of the disease. As part of the innate immune system, neutrophils play a critical role in the defense against infections through the production of reactive oxygen species (ROS), the formation of NETs (Neutrophil extracellular traps) and their ability to release cytotoxic mediators through degranulation. Neutrophil generated ROS was previously shown to aggravate the symptoms of colitis. Lowering the neutrophils production of ROS, therefore becomes an attractive potential therapy for colitis. To test this, we utilized a nanoparticle-based neutrophil-specific targeting platform developed in our lab. We used this platform to deliver compounds capable of reducing ROS production, specifically in neutrophils. We show that the delivery of such compounds, in a neutrophil-specific fashion, significantly reduces the progression of the disease in a colitis mouse model. Still under development, this platform shows great promise and our data suggests that modulation of neutrophil function may serve as a novel mode of immunotherapy for colitis as well as for a wide range of clinical conditions where neutrophils play a critical role.