[연구필요성]
Treatment of inflammatory bowel disease including ulcerative colitis and Crohn’s diseaseAlthough various immunomodulators have been developed and developed, it is essential to develop drugs with new mechanisms because each patient’s drug response varies. Hydrogen sulfide is attracting attention as a new therapeutic candidate due to its excellent anti-inflammatory effect in the gastrointestinal tract. However, it was necessary to develop a system that stably delivers materials that release hydrogen sulfide to the desired area.
[연구성과/기대효과]
Professor Hyungjun Lim’s research team Development of a nanopharmaceutical that can stably contain a hydrogen sulfide donor and target the spleen, the largest lymphatic organand this drug effectively induced systemic immunomodulation. Through this study, it was confirmed that this nanopharmaceutical 1) delivers hydrogen sulfide-releasing drugs to the spleen and inflammatory sites and 2) shows efficient systemic and local immune regulation and tissue restoration effects in the colitis model.
[본문]
Hydrogen sulfide, a gas carrier, is involved in various physiological processes and has anti-inflammatory and cytoprotective effects, especially in the gastrointestinal tract. So far, hydrogen sulfide-releasing drugs have shown excellent therapeutic effects in gastrointestinal disease experiments, but only studies directly injected into the inflammatory site have been reported, and have several limitations. The research team developed stable, spleen-targeted hydrogen sulfide delivery nanoparticles optimized to induce systemic immune effects.
Intravenously injected nanoparticles are naturally captured by phagocytosis of immune cells such as macrophages and dendritic cells. For the foregoing reasons, nanoparticles are in the limelight as effective materials for immunoregulation of various diseases. In addition, studies targeting the spleen, the largest lymphoid organ, are being actively conducted to increase the immunomodulatory effect of nanoparticles. The research team confirmed the components and ratios of the liposomes suitable for targeting the spleen, carrying hydrogen sulfide-releasing substances, and confirmed the excellent spleen targeting efficiency through nuclear medicine imaging through radioisotope labeling.
Professor Hyungjun Lim’s team developed nanoparticles with excellent spleen-targeting efficiency while effectively and stably supporting hydrogen sulfide-releasing materials through comparative experiments on the characteristics of various components and ratios of liposomes. In cell experiments, the nanoparticles effectively induced differentiation into anti-inflammatory macrophages and also induced differentiation into regulatory T cells with anti-inflammatory action in both normal mice and colitis model mice. In the colitis model treatment experiment, it was confirmed that the spleen-targeting nanoparticles have a superior therapeutic effect than the existing inflammatory site-targeting nanoparticles. In addition, through transcript level analysis, it was confirmed that inflammation-related genes were reduced in the colon tissue of the colitis model administered with the spleen-targeting nanoparticles, and an increase in genes reflecting colon tissue restoration was confirmed, resulting in excellent therapeutic effects. .
The research was published in February 2023 in ‘ACS Nano’, an international journal in the field of nanoscience. In addition, this study was carried out with the support of the Convergence Science Research Institute of the University Key Research Institute Support Project and the Innovative New Drug Convergence Research Center of the 4th Phase BK21 Project.