Yoo, Soyeon Faisal, Muhammad Bae, Seo­Hyeon Youn, Kounghwa Park, Hyo­Jung Kwon, Sung Pil Hwang, Il Kwon Lee, Jisun Kim Hyeong Jun Nam, Jae­Hwan Keum, Gyochang Bang, Eun­Kyoung 2024-11-07T11:00:27Z 2024-11-07T11:00:27Z 2024-11-07 2025-03 2192-2640 https://pubs.kist.re.kr/handle/201004/151008 Following their approval by the Food and Drug Administration, lipid nanoparticles (LNPs) have emerged as promising tools for delivering mRNA vaccines and therapeutics. Ionizable lipids are among the essential components of LNPs, as they play crucial roles in encapsulating mRNA and facilitating its release into the cytosol. In this study, 17 innovative ionizable lipids using vitamin B5 are designed as the core structure, aiming to reduce toxicity, to maintain vaccine efficiency, and to ensure synthetic feasibility. The top-performing LNP in terms of mRNA vaccine delivery in the mouse model is LNP 5097, which is generated by incorporating ionizable lipid I97. mRNA⊂LNP 5097 demonstrates favorable structural and physicochemical properties, high mRNA transfection efficiency, and long-term stability. Moreover, mRNA⊂LNP 5097 specifically delivers the mRNA to the spleen and lymph nodes in model mice, induces balanced Th1/Th2 immune responses, and elicits the production of high levels of neutralizing antibodies with low toxicity. The findings here suggest the high utility of LNP 5097, which includes novel vitamin B5-derived ionizable lipids with reduced toxicity, in mRNA vaccine research for both infectious diseases and cancer. English Wiley-Blackwell Novel Less Toxic, Lymphoid Tissue-Targeted Lipid Nanoparticles Containing a Vitamin B5-Derived Ionizable Lipid for mRNA Vaccine Delivery Article 10.1002/adhm.202570043 1 Advanced Healthcare Materials, v.14, no.7 Advanced Healthcare Materials 14 7 N scie scopus Engineering, Biomedical Nanoscience & Nanotechnology Materials Science, Biomaterials Engineering Science & Technology - Other Topics Materials Science Article; Early Access IMMUNE-RESPONSES PANTOTHENIC-ACID DAMAGE vitamin B5 ionizable lipids lipid nanoparticles mRNA vaccine targeted delivery