Synthesis of a dendritic cell-targeted self-assembled polymeric nanoparticle for selective delivery of mRNA vaccines to elicit enhanced immune responses

• Published in: Chemical science (Cambridge) Vol. 15; no. 29; pp. 11626 - 11632
• Main Authors: Fan, Chen-Yo, Wang, Szu-Wen, Chung, Cinya, Chen, Jia-Yan, Chang, Chia-Yen, Chen, Yu-Chen, Hsu, Tsui-Ling, Cheng, Ting-Jen R, Wong, Chi-Huey
• Format: Journal Article
• Language: English
• Published: England Royal Society of Chemistry 24.07.2024; The Royal Society of Chemistry
• Subjects: Chemical synthesis; Chemistry; Copolymers; Dendritic structure; Immune system; Lipids; Nanoparticles; Self-assembly; Vaccines
• ISSN: 2041-6520; 2041-6539
• DOI: 10.1039/d3sc06575h

Recent development of SARS-CoV-2 spike mRNA vaccines to control the pandemic is a breakthrough in the field of vaccine development. mRNA vaccines are generally formulated with lipid nanoparticles (LNPs) which are composed of several lipids with specific ratios; however, they generally lack selective delivery. To develop a selective delivery method for mRNA vaccine formulation, we reported here the synthesis of polymeric nanoparticles (PNPs) composed of a guanidine copolymer containing zwitterionic groups and a dendritic cell (DC)-targeted aryl-trimannoside ligand for encapsulation and selective delivery of an mRNA to dendritic cells. A DC-targeted SARS-CoV-2 spike mRNA-PNP vaccine was shown to elicit a stronger protective immune response in mice compared to the traditional mRNA-LNP vaccine and those without the selective delivery design. It is anticipated that this technology is generally applicable to other mRNA vaccines for DC-targeted delivery with enhanced immune response. Dendritic cell-targeted mRNA-PNP vaccines.