PMID- 36194390 OWN - NLM STAT- MEDLINE DCOM- 20221027 LR - 20221222 IS - 1530-6992 (Electronic) IS - 1530-6984 (Linking) VI - 22 IP - 20 DP - 2022 Oct 26 TI - Phosphatidylserine Lipid Nanoparticles Promote Systemic RNA Delivery to Secondary Lymphoid Organs. PG - 8304-8311 LID - 10.1021/acs.nanolett.2c03234 [doi] AB - Secondary lymphoid organs (SLOs) are an important target for mRNA delivery in various applications. While the current delivery method relies on the drainage of nanoparticles to lymph nodes by intramuscular (IM) or subcutaneous (SC) injections, an efficient mRNA delivery carrier for SLOs-targeting delivery by systemic administration (IV) is highly desirable but yet to be available. In this study, we developed an efficient SLOs-targeting carrier using phosphatidylserine (PS), a well-known signaling molecule that promotes the endocytic activity of phagocytes and cellular entry of enveloped viruses. We adopted these biomimetic strategies and added PS into the standard four-component MC3-based LNP formulation (PS-LNP) to facilitate the cellular uptake of immune cells beyond the charge-driven targeting principle commonly used today. As a result, PS-LNP performed efficient protein expression in both lymph nodes and the spleen after IV administration. In vitro and in vivo characterizations on PS-LNP demonstrated a monocyte/macrophage-mediated SLOs-targeting delivery mechanism. FAU - Luozhong, Sijin AU - Luozhong S AUID- ORCID: 0000-0001-8697-9480 AD - Meinig School of Biomedical Engineering, Cornell University, Ithaca, New York 14853, United States. FAU - Yuan, Zhefan AU - Yuan Z AUID- ORCID: 0000-0002-4724-6214 AD - Meinig School of Biomedical Engineering, Cornell University, Ithaca, New York 14853, United States. FAU - Sarmiento, Tara AU - Sarmiento T AD - Meinig School of Biomedical Engineering, Cornell University, Ithaca, New York 14853, United States. FAU - Chen, Yu AU - Chen Y AD - Department of Materials Science and Engineering, Cornell University, Ithaca, New York 14853, United States. FAU - Gu, Wenchao AU - Gu W AUID- ORCID: 0000-0002-0967-1682 AD - Meinig School of Biomedical Engineering, Cornell University, Ithaca, New York 14853, United States. FAU - McCurdy, Caleb AU - McCurdy C AD - Meinig School of Biomedical Engineering, Cornell University, Ithaca, New York 14853, United States. FAU - Gao, Wenting AU - Gao W AD - Department of Microbiology and Immunology, Cornell University, Ithaca, New York 14853, United States. FAU - Li, Ruoxin AU - Li R AD - Meinig School of Biomedical Engineering, Cornell University, Ithaca, New York 14853, United States. FAU - Wilkens, Stephan AU - Wilkens S AD - Department of Biochemistry and Molecular Biology, SUNY Upstate Medical University, Syracuse, New York 13210, United States. FAU - Jiang, Shaoyi AU - Jiang S AUID- ORCID: 0000-0001-9863-6899 AD - Meinig School of Biomedical Engineering, Cornell University, Ithaca, New York 14853, United States. LA - eng GR - S10 OD025049/OD/NIH HHS/United States GR - R35 GM141908/GM/NIGMS NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, Non-P.H.S. DEP - 20221004 PL - United States TA - Nano Lett JT - Nano letters JID - 101088070 RN - 0 (Lipid Nanoparticles) RN - 0 (Phosphatidylserines) RN - 0 (RNA, Small Interfering) RN - 0 (RNA, Messenger) SB - IM MH - *Phosphatidylserines MH - *Nanoparticles/chemistry MH - RNA, Small Interfering/genetics MH - RNA, Messenger/genetics OTO - NOTNLM OT - cell-targeting delivery OT - lipid nanoparticles OT - mRNA delivery OT - secondary lymphoid organs EDAT- 2022/10/05 06:00 MHDA- 2022/10/28 06:00 CRDT- 2022/10/04 11:22 PHST- 2022/10/05 06:00 [pubmed] PHST- 2022/10/28 06:00 [medline] PHST- 2022/10/04 11:22 [entrez] AID - 10.1021/acs.nanolett.2c03234 [doi] PST - ppublish SO - Nano Lett. 2022 Oct 26;22(20):8304-8311. doi: 10.1021/acs.nanolett.2c03234. Epub 2022 Oct 4.