Folic acid ameliorates the immunogenicity of PEGylated liposomes

As PEGylated liposomes have witnessed remarkable advancements in drug delivery, their immunogenicity has emerged as a notable challenge. In this study, we discovered that a simple pre-injection of folic acid (FA) effectively mitigated the immunogenicity of PEGylated liposomes and enhanced their in vivo performance by tolerating splenic marginal zone B cells. FA specifically inhibited the internalization of PEGylated liposomes by splenic marginal zone B cells, thereby reducing splenic lymphocyte proliferation and specific IgM secretion. This modulation alleviated IgM-mediated accelerated blood clearance and adverse accumulation of the PEGylated liposomes in the skin. These findings provide new insights into the immunomodulatory effects of FA and promising avenues to enhance the efficacy and safety of PEGylated liposomal nanomedicines.