Enhance Intracellular Delivery of Messenger RNA (mRNA)
Key Words: LNPs (Lipid Nanoparticles) and eLNP (C-24 alkyl phytosterols incorporated LNPs)
Endosomal sequestration of lipid-based nanoparticles (LNPs) stays as a challenging obstacle to drug delivery systems.
In a significant work done by Siddharth Patel et al. it is shown that for keeping the efficient transfection, incorporating C-24 alkyl phytosterols into LNPs (eLNPs) increases gene transfection. They also showed the length of the alkyl tail. The flexibility of the sterol ring and polarity due to -OH groups can also improve the cells' transfection of lipid nanoparticles 1.
In another part of the study, the group ran Cryogenic Transmission Electron Microscopy (cryo-TEM) to study the particles' morphology. Cryo-TEM showed a polyhedral profile for eLNPs when compared to spherical lipid nanoparticles, while x-ray scattering demonstrates a small variation in the core structure of the formulations. eLNPs presented improved cellular uptake and retention, driving to a steady discharge from the endosomes over time 1.
In this work, the 3D single-particle following demonstrated improved intracellular diffusivity of eLNPs comparative to LNPs. These results advised that eLNP traffic to useful pathways for leakage in comparison with the LNPs. Their findings also showed the significance of cholesterol in the subcellular transport of LNPs transport mRNA. Moreover, they highlighted the necessity for a better understanding of these lipid nanoparticles' surface composition and structural properties and their subcellular communications, which enable strategies to enhance endosomal escape1.
For more details, visit the paper, which is an entirely open source by nature communication.
- Patel, S., Ashwanikumar, N., Robinson, E., Xia, Y., Mihai, C., Griffith, J.P., Hou, S., Esposito, A.A., Ketova, T., Welsher, K. and Joyal, J.L., 2020. Naturally-occurring cholesterol analogues in lipid nanoparticles induce polymorphic shape and enhance intracellular delivery of mRNA. Nature communications, 11(1), pp.1-13.