Dendritic Cell‐Mimicking Nanoparticles Promote mRNA Delivery to Lymphoid Organs

• Published in: Advanced science Vol. 10; no. 33; pp. e2302423 - n/a
• Main Authors: Cao, Yiming, Long, Jinrong, Sun, Huisheng, Miao, Yiqi, Sang, Ye, Lu, Haitao, Yu, Changxiao, Zhang, Zhen, Wang, Lin, Yang, Jing, Wang, Shengqi
• Format: Journal Article
• Language: English
• Published: Weinheim John Wiley & Sons, Inc 01.11.2023; Wiley
• Subjects: Antigens; Bone marrow; Cytotoxicity; delivery; dendritic cell membrane; Dendritic cells; Efficiency; Flow cytometry; Immune system; Immunotherapy; Lipids; Lymphatic system; lymphoid organs; Membranes; mRNA vaccine; mRNA vaccines; Nanoparticles; Optimization; Pathogens; Protein expression; Proteins; Severe acute respiratory syndrome coronavirus 2; Spleen; Transmission electron microscopy
• ISSN: 2198-3844; 2198-3844
• DOI: 10.1002/advs.202302423

Spleen and lymphoid organs are important targets for messenger RNA (mRNA) delivery in various applications. Current nanoparticle delivery methods rely on drainage to lymph nodes from intramuscular or subcutaneous injections. In difficult‐to‐transfect antigen‐presenting cells (APCs), such as dendritic cells (DCs), effective mRNA transfection remains a significant challenge. In this study, a lymphatic targeting carrier using DC membranes is developed, that efficiently migrated to lymphoid organs, such as the spleen and lymph nodes. The nanoparticles contained an ionizable lipid (YK009), which ensured a high encapsulation efficacy of mRNA and assisted mRNA with endosomal escape after cellular uptake. Dendritic cell‐mimicking nanoparticles (DCMNPs) showed efficient protein expression in both the spleen and lymph nodes after intramuscular injections. Moreover, in immunized mice, DCMNP vaccination elicited Spike‐specific IgG antibodies, neutralizing antibodies, and Th1‐biased SARS‐CoV‐2‐specific cellular immunity. This work presents a powerful vaccine formula using DCMNPs, which represents a promising vaccine candidate for further research and development. Dendritic cell‐mimicking nanoparticles (DCMNPs), which can effectively deliver mRNA to lymphatic organs, are developed as a novel mRNA delivery carrier. The DCMNPs are formed by encapsulating mRNA in a carrier composed of DC membrane, ionizable lipid YK009 and DOPE. DCMNPs with SARS‐CoV‐2 Spike protein mRNA can triggered a robust neutralizing antibody and SARS‐CoV‐2‐specific cell immunity in mice.