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Quaternization drives spleen-to-lung tropism conversion for mRNA-loaded lipid-like nanoassemblies.
Huang, Yixuan; Wu, Jiacai; Li, Sanpeng; Liu, Zhen; Li, Zhenghua; Zhou, Boping; Li, Bin.
Afiliación
  • Huang Y; 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.
  • Wu J; 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.
  • Li S; School of Medicine, Southern University of Science and Technology, Shenzhen, 518055, China.
  • Liu Z; 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.
  • Li Z; 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.
  • Zhou B; 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.
  • Li B; 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.
Theranostics ; 14(2): 830-842, 2024.
Article en En | MEDLINE | ID: mdl-38169552
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Bazo / Nanopartículas Límite: Animals Idioma: En Revista: Theranostics Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Australia
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Bazo / Nanopartículas Límite: Animals Idioma: En Revista: Theranostics Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Australia