@article{Wang2024, 
author = {Fazhan Wang and Meng Zhang and Meiling Tian and Jia Lou and Longze Pan and Xiaoke Gao and Lijing Zhang and Xiaohan Lou and Linyu Zhu and Yuqiao Sheng and Ming Wang and Rui Xue and Wenjing Deng and Shuai Shao and Zhihai Qin},
title = {Natural long-chain saturated fatty acids doped LNPs enabling spleen selective mRNA translation and potent cancer immunotherapy},
year = {2024},
journal = {Nano Research},
volume = {17},
number = {3},
pages = {1804-1817},
keywords = {cancer immunotherapy, mRNA vaccine, lipid nanoparticles, spleen, long-chain saturated fatty acid},
url = {https://www.sciopen.com/article/10.1007/s12274-023-6111-2},
doi = {10.1007/s12274-023-6111-2},
abstract = {Rationally tailored lipid nanoparticles (LNPs) with efficient and tunable delivery of mRNA in vivo are crucial for mRNA vaccines. Selective expression of antigenic protein in lymphoid tissues/organs could improve the immunostimulatory efficacy and safety of LNPs-based mRNA vaccines. Inspired by the metabolic behavior that long-chain saturated fatty acids tending to enter lymphoid tissue rather than the liver, we developed fatty acid-doped LNPs capable of mediating differential protein expressions in the liver and spleen when administered intravenously. When the molar ratio of saturated fatty acid located 60%–70%, the doped LNPs achieved the spleen selective mRNA translation. The mechanism could be attributed to the different cellular uptake behaviors of saturated fatty acids in hepatocytes. Immunization with a model antigen (ovalbumin) mRNA-loaded spleen selective LNPs, we observed enhanced antigen-specific T cell immune responses, and potent immunotherapeutic and immunoprophylactic efficacy in the mouse lymphoma model. Our natural long-chain saturated fatty acids metabolic characteristics-inspired design of LNPs for spleen-selective mRNA vaccines delivery will provide references for designing mRNA vaccines with high efficacy and safety for tumor immunotherapy.}
}