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Review
. 2024 Sep 22;25(18):10166.
doi: 10.3390/ijms251810166.

Development of mRNA Lipid Nanoparticles: Targeting and Therapeutic Aspects

Yaping Liu  1   2 , Yingying Huang  1   2 , Guantao He  2   3 , Chun Guo  1 , Jinhua Dong  1 , Linping Wu  2   4
Affiliations
Review

Development of mRNA Lipid Nanoparticles: Targeting and Therapeutic Aspects

Yaping Liu et al. Int J Mol Sci. .

Abstract

Lipid nanoparticles (LNPs) have emerged as leading non-viral carriers for messenger RNA (mRNA) delivery in clinical applications. Overcoming challenges in safe and effective mRNA delivery to target tissues and cells, along with controlling release from the delivery vehicle, remains pivotal in mRNA-based therapies. This review elucidates the structure of LNPs, the mechanism for mRNA delivery, and the targeted delivery of LNPs to various cells and tissues, including leukocytes, T-cells, dendritic cells, Kupffer cells, hepatic endothelial cells, and hepatic and extrahepatic tissues. Here, we discuss the applications of mRNA-LNP vaccines for the prevention of infectious diseases and for the treatment of cancer and various genetic diseases. Although challenges remain in terms of delivery efficiency, specific tissue targeting, toxicity, and storage stability, mRNA-LNP technology holds extensive potential for the treatment of diseases.

Keywords: cancer; genetic diseases; infectious disease; lipid nanoparticles; mRNA vaccine.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Composition and models of mRNA lipid nanoparticles: (a) Chemical structure of representative lipids used for delivery of therapeutic nucleic acids. (b) Multilamellar vesicle (onion-like). (c) Particle with a nanostructured core. (d) Homogeneous core–shell structure. (b–d) are reprinted with permission from [15]. Copyright 2023 Elsevier Inc.
Figure 2
Figure 2
The mRNA–LNP vaccine immune response process. Reprinted with permission from [35]. Copyright 2022 Elsevier Inc.
Figure 3
Figure 3
Representative surface modification strategies for LNP targeting. Reprinted with permission from [39]. Copyright 2023 Wiley.
Figure 4
Figure 4
Selective organ targeting (SORT) technology achieves liver- and lung-specific mRNA delivery. Reprinted with permission from [63]. Copyright 2023 Elsevier Inc.
Figure 5
Figure 5
Key steps in the cancer immune cycle. Reprinted with permission from [123]. Copyright 2023 Elsevier Inc.
Figure 6
Figure 6
Schematic illustration of the mRNA–LNP cancer vaccines. Reprinted with permission from [39]. Copyright 2023 Wiley.
Figure 7
Figure 7
Representative administration routes and their applications of mRNA–LNP.
See this image and copyright information in PMC

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