The Double-Edged Sword Effect of Macrophage Targeting Delivery System in Different Macrophage Subsets Related Diseases

Abstract Background: Monocyte/macrophage-targeting delivery systems (MTDSs) have been focused upon as an emerging routine for delivering drugs to treat various macrophage-related diseases. However, the ability of MTDSs to distinguish different macrophage-related diseases and their impact on macrophage function and disease progression have not been systematically revealed, which is important for actively targeted therapeutic or diagnostic strategies. Results: Herein, we used dextran-modified polystyrene nanoparticles (DEX-PS) to demonstrate that modification of nanoparticles by dextran can specifically enhance their recognition by M2 macrophages in vitro , but it is obstructed by monocytes in peripheral blood according to in vivo assays. DEX-PS not only targeted and became distributed in tumors, an M2 macrophage-related disease, but was also highly distributed in an M1 macrophage-related disease, namely acute peritonitis. Thus, DEX-PS acts as a double-edged sword in these two different diseases by reeducating macrophages to a pro-inflammatory phenotype. Conclusions: Our results suggest that MTDSs, even those designed based on differential expression of receptors on specific macrophage subtypes, lack the ability to distinguish different macrophage subtype-related diseases in vivo . In addition to the potential impact of these carrier materials on macrophage function, studies of MTDSs should pay greater attention to the distribution of nanoparticles in non-target macrophage-infiltrated disease sites and their impact on disease processes.