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Zwitterionic Polymer-Decorated Lipid Nanoparticles for mRNA Delivery in Mammalian Cells
Phim-On Khunsuk1, Chitsuda Pongma2, Tanapat Palaga3,4
1Program in Petrochemistry and Polymer Science, Faculty of Science, Chulalongkorn University, Phayathai Road, Pathumwan, Bangkok 10330, Thailand.
Biomacromolecules
|November 13, 2023
Summary
Researchers developed non-poly(ethylene glycol) (PEG) lipid nanoparticles (LNPs) using zwitterionic polymers. These PMPC-LNPs show promise as safe and effective mRNA carriers, overcoming PEG allergy challenges.
Area of Science:
- Biotechnology
- Materials Science
- Nanomedicine
Background:
- Lipid nanoparticles (LNPs) are crucial for mRNA delivery.
- Poly(ethylene glycol) (PEG) coatings enhance LNP stability but can cause immune reactions (PEG allergies).
- Developing non-PEG alternatives is essential for safer mRNA vaccines and therapeutics.
Purpose of the Study:
- To create and evaluate novel non-PEG lipid nanoparticles using zwitterionic polymers.
- To assess the physicochemical properties, biocompatibility, and mRNA transfection efficiency of these new LNPs.
- To demonstrate the potential of zwitterionic polymer-conjugated LNPs as advanced mRNA carriers.
Main Methods:
- Conjugation of 1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine (DPPE) with poly(2-methyacryloyloxyethyl phosphorylcholine) (PMPC) of varying chain lengths.
- Formulation of PMPC-LNPs and characterization of their size, charge, stability, and stealthiness.
- In vitro assessment of PMPC-LNPs' cytotoxicity using HEK293T cells and inflammatory response using THP-1 cells.
- Evaluation of mRNA transfection efficiency compared to traditional PEG-LNPs.
Main Results:
- Spherical PMPC-LNPs (144-255 nm) with neutral charge and good stability (28 days at 4°C) were successfully formulated.
- PMPC coatings demonstrated significant antifouling properties, achieving near-perfect stealthiness.
- PMPC-LNPs exhibited no toxicity to HEK293T cells and did not induce inflammatory responses in THP-1 cells.
- mRNA transfection efficiency of PMPC-LNPs surpassed that of PEG-LNPs.
Conclusions:
- Zwitterionic polymer-conjugated DPPE-PMPC lipids effectively form stable, non-toxic LNPs.
- These PMPC-LNPs offer superior mRNA delivery performance compared to PEG-LNPs.
- The developed PMPC-LNPs represent a promising, potentially hypoallergenic alternative for mRNA-based therapies and vaccines.
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