Targeted magnesium ion delivery to macrophages via efferocytosis-mimicking nanoparticles for anti-inflammatory regulation 4167

Abstract Description Macrophages play a vital role in protecting the host through pyroptosis, a self-sacrificial response to aberrant stimuli. This form of death results in the release of inflammatory cytokines that attracts immune cells and activates downstream immune responses. However, pyroptosis can also result in serious localized and systemic damage due to its rapidity and nonspecific nature. In this study, we introduce an innovative design of a magnesium ion-based nano-supplier, referred to as MgC@PS, which is capable of targeted intracellular delivery to macrophages by mimicking the behavior of efferocytosis. The surface coating with dioleoyl phosphatidylserine allows MgC@PS to bio-mimic apoptotic cell membranes, leading to efficient ingestion by macrophages. Our data showed that MgC@PS suppressed pyroptosis effectively and reduced serious inflammatory reactions. Single-cell RNA sequencing and cytokine profiling showed that MgC@PS could promote the phenotypic transition of macrophages from a pro-inflammatory state toward an anti-inflammatory state. In vivo therapeutic investigations showed decreased liver fibrosis and reduced ulcerative colitis by MgC@PS treatment. These findings position MgC@PS as a promising approach toward targeted intracellular delivery of magnesium ion into macrophages for treatment of inflammation. Further experiments are being conducted to elucidate the exact mechanisms by which MgC@PS modulates anti-inflammatory responses in macrophages. Funding Sources Supported by North Carolina Biotechnology Center 2024-FLG-0066; Lung Cancer Initiative; UNCG Internal Research Award Topic Categories Technological Innovations in Immunology (TECH)