On March 3, reporters learned from the Southwest Hospital of the Army Medical University that the team led by Professor Chen Lei from the Department of Gastroenterology, in collaboration with Professor Zhang Dinglin of the Army Medical University, published a research paper titled "Targeted Delivery of Programmed Death Ligand-1 for the Treatment of Acute and Chronic Colitis" in the international academic journal Nature Communications. This study introduces, for the first time, a reactive oxygen species-responsive nanomaterial capable of precisely delivering programmed death ligand-1 to the sites of intestinal inflammation, effectively alleviating symptoms of colitis and offering a new strategy for the treatment of inflammatory bowel disease (IBD).
"Inflammatory bowel disease is a chronic inflammatory condition of the gastrointestinal tract that recurs over time, mainly including ulcerative colitis and Crohn's disease. Patients often suffer from abdominal pain, diarrhea, and bloody stools, and in severe cases, may experience complications like gastrointestinal strictures and perforations," explained Professor Chen Lei. The chronic and difficult-to-cure nature of the disease severely impacts the patients' quality of life, posing significant burdens on the patients and their families.
According to Professor Chen, a substantial amount of research has been conducted on inflammatory bowel disease. Studies have shown that drugs containing programmed death ligand-1, though effective in reducing inflammation, can lead to a decrease in immunity over long-term use, potentially endangering lives. Therefore, developing safe and low-side-effect drugs for the clinical treatment of IBD has become a major focus.
"Numerous studies have indicated that inflammatory responses are often accompanied by the excessive production of reactive oxygen species. This led us to wonder whether we could use a material responsive to reactive oxygen species to precisely deliver the drug programmed death ligand-1 to the sites of intestinal inflammation," said Professor Chen. In collaboration with Professor Zhang Dinglin, who has extensive experience in drug delivery systems, they developed a reactive oxygen species-responsive and scavenging nanomaterial composed of α-cyclodextrin and 4-hydroxymethyl phenylboronic acid pinacol ester. They explored the therapeutic effects of this material on mice with acute and chronic colitis.
"During our research, we combined the programmed death ligand-1 with the reactive oxygen species-responsive nanomaterial to create a new nanodrug," Professor Chen remarked. Upon administering this new nanodrug to mice, they discovered that, compared to the injection of drugs containing programmed death ligand-1 alone, the new nanodrug could be precisely delivered "point-to-point" to the sites of colitis. It could alleviate symptoms of colitis by adjusting the ratio of immune cells and reshaping the gut microbiota to the greatest extent possible. More importantly, the study also found that delivering programmed death ligand-1 in this manner could reduce its nonspecific distribution in other organs, lowering the risk of lung infections and effectively reducing the side effects of such protein drugs, providing a new direction for treating inflammatory bowel disease.
