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Theranostics 2024; 14(2):830-842. doi:10.7150/thno.90071 This issue Cite

Research Paper

Quaternization drives spleen-to-lung tropism conversion for mRNA-loaded lipid-like nanoassemblies

Yixuan Huang1, Jiacai Wu1,2, Sanpeng Li1, Zhen Liu1, Zhenghua Li1, Boping Zhou1,2, Bin Li1,2,✉

1. Department of Infectious Disease, Shenzhen People's Hospital, The First Affiliated Hospital of Southern University of Science and Technology & The Second Clinical Medical College of Jinan University, Shenzhen 518020, China.
2. School of Medicine, Southern University of Science and Technology, Shenzhen, 518055, China.

✉ Corresponding author: E-mail address: libinsustech.edu.cn (B. Li).

Citation:
Huang Y, Wu J, Li S, Liu Z, Li Z, Zhou B, Li B. Quaternization drives spleen-to-lung tropism conversion for mRNA-loaded lipid-like nanoassemblies. Theranostics 2024; 14(2):830-842. doi:10.7150/thno.90071. https://www.thno.org/v14p0830.htm
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Abstract

Graphic abstract

Background: As the overwhelming majority of advanced mRNA delivery systems are preferentially accumulated in the liver, there is an accelerating growth in the demand for the development of non-liver mRNA delivery platforms.

Methods: In this study, we prepared cationic lipid-like nanoassemblies through a N-quaternizing strategy. Their physicochemical properties, in vitro mRNA delivery efficiency, and organ tropism in mice were investigated.

Results: Introduction of quaternary ammonium groups onto lipid-like nanoassemblies not only enhances their mRNA delivery performance in vitro, but also completely alters their tropism from the spleen to the lung after intravenous administration in mice. Quaternized lipid-like nanoassemblies exhibit ultra-high specificity to the lung and are predominantly taken up by pulmonary immune cells, leading to over 95% of exogenous mRNA translation in the lungs. Such mRNA delivery carriers are stable even after more than one-year storage at ambient temperature.

Conclusions: Quaternization provides an alternative method for design of new lung-targeted mRNA delivery systems without incorporation of targeting ligands, which should extend the therapeutic applicability of mRNA to lung diseases.

Keywords: quaternization, lipid-like nanoassembly, systemic mRNA delivery, lung targeting, ultra-high selectivity

Citation styles

APA
Huang, Y., Wu, J., Li, S., Liu, Z., Li, Z., Zhou, B., Li, B. (2024). Quaternization drives spleen-to-lung tropism conversion for mRNA-loaded lipid-like nanoassemblies. Theranostics, 14(2), 830-842. https://doi.org/10.7150/thno.90071.

ACS
Huang, Y.; Wu, J.; Li, S.; Liu, Z.; Li, Z.; Zhou, B.; Li, B. Quaternization drives spleen-to-lung tropism conversion for mRNA-loaded lipid-like nanoassemblies. Theranostics 2024, 14 (2), 830-842. DOI: 10.7150/thno.90071.

NLM
Huang Y, Wu J, Li S, Liu Z, Li Z, Zhou B, Li B. Quaternization drives spleen-to-lung tropism conversion for mRNA-loaded lipid-like nanoassemblies. Theranostics 2024; 14(2):830-842. doi:10.7150/thno.90071. https://www.thno.org/v14p0830.htm

CSE
Huang Y, Wu J, Li S, Liu Z, Li Z, Zhou B, Li B. 2024. Quaternization drives spleen-to-lung tropism conversion for mRNA-loaded lipid-like nanoassemblies. Theranostics. 14(2):830-842.

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