Longuide Biopharma Corporation has developed an extensive library of thousands of novel ionizable lipid candidates through the application of combinatorial chemistry. We extended chemical diversity of the ionizable lipids by incorporating diverse biodegradable linkers and by fine- tuning the position of linkers and the hydrophobicity of the tails. Inspired by the two FDA-approved lipids used in COVID-19 mRNA vaccines, SM-102 and ALC-0315, hydroxyl group were introduced to the amine headgroups of LLNP lipids to enhance interaction with mRNA molecules via hydrogen bonding, thus leading to higher mRNA encapsulating efficiency. Next, by tuning the ratio of lipid components of LNP and employing in vivo high-throughput screening, we have identified several promising lipid candidates that target specific organs or tissues, including the lung, spleen, liver, lymph node, and adipose tissue. The lung-targeting delivery platform shows potential in treating pulmonary diseases such as lung cancer, cystic fibrosis, and lung infection diseases, while spleen and lymph node-targeting delivery platforms can be utilized in cancer immunotherapy. Additionally, the adipose tissue-targeting delivery platform holds promise in the treatment of diabetes and endocrine diorders.