Spleen-targeted mRNA delivery via long-chain PEGylated lipids at low molar ratio enhances antitumor immunity against melanoma

T cell populations, and significantly inhibited tumor growth in a B16-ovalbumin (OVA) melanoma model. Collectively, our results establish a rational strategy via precise PEGylated lipid engineering to redirect LNP biodistribution from the liver to the spleen. These findings validate the spleen as a critical target for mRNA vaccines and provide a versatile platform for next-generation cancer immunotherapies.