Repolarization of microglia from M1 to M2 by hyaluronic acid-modified lipid nanoparticles delivering IL-10 mRNA

IL10 is an anti-inflammatory cytokine that helps regulate immune response and maintains homeostasis in microglia cells.The microglia cells have different phases of M1 M2 with tissue damage and repair, respectively.Previous studies have shown that IL10 deficiency in microglia environment can lead to elevate their proinflammatory function.The IL10 mRNA is a potential targeting mRNA for M1-activated microglia to suppress their excessive proinflammatory activity and repolarize them to M2 phase.The LNPs as mRNA delivery system showed promising therapeutic potential e.g., mRNA vaccines.However, they could cause unwanted immunogenic signals for activated microglia. On the other hand, the M1-microglia expressed CD44 while M2 not.Hyaluronate(HA) is a CD44 receptor with intrinsic immunomodulatory properties.Based on this feature, in this work the LNPs were decorated with HA as CD44 targeting agent.By these CD44-targeting LNPs it is feasible to target M1activated microglia cells that have e ssential role in chronic neurodegenerative inflammatory disorders such as glaucoma.