BiomacromoleculesNov 27, 2025

Lipid Nanoparticles without PEG for mRNA Delivery Using Water-Loving Sulfoxide Polymer Coatings

mRNA Technology Weekly Brief ↗PubMed ↗DOI ↗

Updated Jan 7, 2026

Abstract

Lipid nanoparticles (LNPs) made with the sulfoxide polymer PMSEA show superior transfection efficiency compared to traditional PEG-based formulations.

PMSEA-DSPE conjugates were developed to improve the stability and immunogenicity of LNPs for mRNA delivery.
These new LNPs exhibited excellent stability and low immunogenicity, which are beneficial for mRNA therapeutics.
PMSEA-LNP formulations demonstrated higher transfection efficiency than PEG-based LNPs in preliminary evaluations.
The findings suggest that PMSEA could be a promising alternative for enhancing mRNA nanocarrier performance.

Simplified

Lipid nanoparticles (LNPs) are the most widely applied nanocarriers for mRNA delivery in clinical use. However, the limited stability and increasingly recognized immunogenicity of PEG-based LNP formulations are potential impediments to the more widespread development of mRNA therapeutics. To address shortcomings in current LNP polymer coatings, we have developed a polymer-lipid conjugate based on the low-fouling sulfoxide polymer poly(2-(methylsulfinyl)ethyl acrylate) (PMSEA). The results show that LNPs formed from the PMSEA-DSPE conjugates with optimized polymer chain length have excellent stability, highly effective shielding, and low immunogenicity, favorable properties for PMSEA-DSPE to be incorporated as a component of mRNA nanocarriers. mRNA-LNP formulations were prepared with PMSEA-DSPE as an alternative to the PEGylated formulations. The stability,behavior, and transfection efficiency of the mRNA nanocarriers were evaluated, with PMSEA providing superior transfection efficiency compared with the PEG equivalents. This work demonstrates the potential of PMSEA mRNA-LNPs for further development as therapeutic delivery vehicles. in vitro

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Lipid Nanoparticles without PEG for mRNA Delivery Using Water-Loving Sulfoxide Polymer Coatings

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