Nanoparticle Internalization Promotes the Survival of Primary Macrophages

Macrophages have emerged as promising therapeutic targets for regulating immune microenvironments. However, tissue-isolated macrophages are plagued by poor survival, which limits the therapeutic efficacy and prevents thorough drug screening and model development. Therefore, developing strategies aimed at prolonging primary macrophage survival is imperative for realizing macrophage therapies and understanding macrophage behavior. We discovered that nanoparticle dosing significantly enhances ex vivo survival of primary macrophages, which is attributed to suppression of apoptosis and is linked to downstream phagocytosis and lysosomal signaling. We report that macrophage survival because of phagocytosis of nanoparticles fabricated with immunologically inert materials does not alter macrophage polarization or lead to aberrant activation. These findings provide a framework for extending the lifespan of primary macrophages ex vivo for drug screening, vaccine studies, and cell therapies. We investigate two groups of bone marrow-derived macrophages (BMMs) with 4 replicates each: 1. Treated with 100 ug/ml polyethylene glycol-based nanoparticles and 2. Untreated