mRNA-Loaded Lipid Nanoparticles Targeting Dendritic Cells for Cancer Immunotherapy

Dendritic cells (DCs) are attractive antigen-presenting cells to be targeted for vaccinations. However, the systemic delivery of mRNA to DCs is hampered by technical challenges. We recently reported that it is possible to regulate the size of RNA-loaded lipid nanoparticles (LNPs) to over 200 nm with...

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Bibliographic Details
Published in:Pharmaceutics 2022-07, Vol.14 (8), p.1572
Main Authors: Sasaki, Kosuke, Sato, Yusuke, Okuda, Kento, Iwakawa, Kazuki, Harashima, Hideyoshi
Format: Article
Language:English
Subjects:
Analysis
Antibodies
Antigens
Cancer
cancer immunotherapy
Cloning
Coronaviruses
COVID-19 vaccines
Cytoplasm
delivery
Dendritic cells
Ethanol
Gene expression
Health aspects
Kinases
Ligands
lipid nanoparticles
Lipids
Messenger RNA
mRNA
Nanoparticles
Particle size
Polyethylene glycol
Proteins
Severe acute respiratory syndrome coronavirus 2
Testing
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Summary:Dendritic cells (DCs) are attractive antigen-presenting cells to be targeted for vaccinations. However, the systemic delivery of mRNA to DCs is hampered by technical challenges. We recently reported that it is possible to regulate the size of RNA-loaded lipid nanoparticles (LNPs) to over 200 nm with the addition of salt during their formation when a microfluidic device is used and that larger LNPs delivered RNA more efficiently and in greater numbers to splenic DCs compared to the smaller counterparts. In this study, we report on the in vivo optimization of mRNA-loaded LNPs for use in vaccines. The screening included a wide range of methods for controlling particle size in addition to the selection of an appropriate lipid type and its composition. The results showed a clear correlation between particle size, uptake and gene expression activity in splenic DCs and indicated that a size range from 200 to 500 nm is appropriate for use in targeting splenic DCs. It was also found that it was difficult to predict the transgene expression activity and the potency of mRNA vaccines in splenic DCs using the whole spleen. A-11-LNP, which was found to be the optimal formulation, induced better transgene expression activity and maturation in DCs and induced clear therapeutic antitumor effects in an E.G7-OVA tumor model compared to two clinically relevant LNP formulations.
ISSN:1999-4923
1999-4923
DOI:10.3390/pharmaceutics14081572