Illuminating endosomal escape of polymorphic lipid nanoparticles that boost mRNA delivery
| Autor: | Marco Herrera, Antony Jozic, Gaurav Sahay, Jeonghwan Kim, Yulia Eygeris |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Cell entry
0303 health sciences Messenger RNA Chemistry Endosome Cell Biomedical Engineering Endosomes 02 engineering and technology Gene delivery 021001 nanoscience & nanotechnology Lipids Article Highly sensitive Cell biology 03 medical and health sciences medicine.anatomical_structure medicine Nanoparticles General Materials Science RNA Messenger 0210 nano-technology 030304 developmental biology Galectin |
| Zdroj: | Biomater Sci |
| ISSN: | 2047-4849 2047-4830 |
| Popis: | Lipid-based nanoparticles (LNPs) for the delivery of mRNA have jumped to the forefront of non-viral gene delivery. Despite this exciting development, poor endosomal escape after LNP cell entry remains an unsolved, rate-limiting bottleneck. Here we report the use of galectin 8-GFP (Gal8-GFP) cell reporter system to visualize the endosomal escaping capabilities of LNPs encapsulating mRNA. LNPs substituted with phytosterols in place of cholesterol exhibited various levels of Gal8 recruitment in the Gal8-GFP reporter system. In live-cell imaging, the results of the LNPs containing β-sitosterol (LNP-Sito) showed a 10-fold increase in detectable endosomal perturbation events when compared to the standard cholesterol LNPs (LNP-Chol), suggesting the superior capability of LNP-Sito to escape from endosomal entrapment. Trafficking studies of these LNPs showed strong localization with late endosomes. This highly sensitive and robust Gal8-GFP reporter system can be a valuable tool to elucidate intricacies of LNP trafficking and ephemeral endosomal escape events, enabling the advancement in gene delivery. |
| Databáze: | OpenAIRE |
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