Fluorinated lipid nanoparticles enable real-time tracking of mRNA delivery and uncover spatiotemporal mechanisms of immune activation
Abstract
Messenger RNA (mRNA) vaccines rely on lipid nanoparticles (LNPs) for in vivo delivery, yet conventional formulations exhibit inefficient tissue targeting, undesired hepatic accumulation, and limited understanding of the delivery–response relationship, constraining their therapeutic precision and safety. Here, we report the development of fluorinated LNPs (FLNPs) that enable real-time tracking of mRNA biodistribution and expression via 19 F magnetic resonance spectroscopy/imaging (NMR/MRI)” rather than “magnetic resonance spectroscopy/MRI (NMR). These FLNPs retain robust protein expression comparable to clinical LNPs, while reducing liver accumulation by 94.6%. By integrating fluorine signal quantification with spatial analysis of mRNA translation and antigen presentation, we establish a direct correlation between carrier localization, antigen expression kinetics, and immune cell trafficking. Specifically, we show that antigen-presenting cells internalize FLNP-mRNA at the injection site and subsequently migrate to draining lymph nodes, enabling localized immune priming with minimal systemic exposure. This work provides mechanistic evidence linking in vivo nanocarrier trafficking with spatiotemporal immune activation, offering insights into how delivery kinetics govern vaccine efficacy. The FLNP platform thus enables both precision mRNA delivery and noninvasive tracking, representing a powerful tool for mechanistic studies and rational design of next-generation mRNA vaccines.
Article Details
Journal Info
Proceedings of the National Academy of Sciences
National Academy of Sciences
Authors (13)
Kairu Xie
State Key Laboratory of Magnetic Resonance Spectroscopy and Imaging, National Center for Magnetic Resonance in Wuhan, Wuhan Institute of Physics and Mathematics, Innovation Academy for Precision Measurement Science and Technology, Chinese Academy of Sciences–Wuhan National Laboratory for Optoelectronics, Huazhong University of Science and Technology
Lijun Zhu
State Key Laboratory of Magnetic Resonance Spectroscopy and Imaging, National Center for Magnetic Resonance in Wuhan, Wuhan Institute of Physics and Mathematics, Innovation Academy for Precision Measurement Science and Technology, Chinese Academy of Sciences–Wuhan National Laboratory for Optoelectronics, Huazhong University of Science and Technology
Mojie Duan
State Key Laboratory of Magnetic Resonance Spectroscopy and Imaging, National Center for Magnetic Resonance in Wuhan, Wuhan Institute of Physics and Mathematics, Innovation Academy for Precision Measurement Science and Technology, Chinese Academy of Sciences–Wuhan National Laboratory for Optoelectronics, Huazhong University of Science and Technology
Yu Fu
Haiqiang Wang
College of Environmental & Resource Sciences
Yuhan Shen
State Key Laboratory of Magnetic Resonance Spectroscopy and Imaging, National Center for Magnetic Resonance in Wuhan, Wuhan Institute of Physics and Mathematics, Innovation Academy for Precision Measurement Science and Technology, Chinese Academy of Sciences–Wuhan National Laboratory for Optoelectronics, Huazhong University of Science and Technology
Yu Li
Ruifang Wang
State Key Laboratory of Magnetic Resonance Spectroscopy and Imaging, National Center for Magnetic Resonance in Wuhan, Wuhan Institute of Physics and Mathematics, Innovation Academy for Precision Measurement Science and Technology, Chinese Academy of Sciences–Wuhan National Laboratory for Optoelectronics, Huazhong University of Science and Technology
Zhong-Xing Jiang
School of Pharmaceutical Sciences
Shizhen Chen
State Key Laboratory of Magnetic Resonance Spectroscopy and Imaging, National Center for Magnetic Resonance in Wuhan, Wuhan Institute of Physics and Mathematics, Innovation Academy for Precision Measurement Science and Technology
Jung Soo Suk
Department of Neurosurgery and Medicine Institute for Neuroscience Discovery, University of Maryland School of Medicine
Daiqin Chen
State Key Laboratory of Magnetic Resonance Spectroscopy and Imaging, National Center for Magnetic Resonance in Wuhan, Wuhan Institute of Physics and Mathematics, Innovation Academy for Precision Measurement Science and Technology, Chinese Academy of Sciences–Wuhan National Laboratory for Optoelectronics, Huazhong University of Science and Technology
Xin Zhou