Layered Nanoparticles Boost mRNA Delivery

Core-shell lipid nanoparticles show early gains in mRNA release but raise new design and safety questions

25 Feb 2026

A redesigned lipid nanoparticle structure is drawing attention in the mRNA field, as early studies suggest it could improve how genetic therapies reach their target inside cells. Researchers in the United States reported that a so-called core-shell architecture, tested in laboratory and animal experiments, doubled measures of endosomal escape and increased functional protein production compared with more conventional formulations.

The findings, presented at a major drug delivery conference, remain preclinical. Still, they address a persistent challenge in mRNA therapeutics. After nanoparticles enter a cell, much of the mRNA cargo can become trapped inside endosomes, cellular compartments that limit its ability to reach the cytoplasm, where protein translation occurs. By redesigning the particle’s physical structure rather than altering individual lipid ingredients alone, the researchers sought to improve the odds that more of the genetic material escapes into the cell’s interior.

The work comes as drugmakers broaden mRNA research beyond vaccines into oncology, rare diseases and other complex conditions. Across these efforts, delivery efficiency has emerged as a central concern. Improved intracellular release, according to researchers in the field, could lower required doses and make manufacturing more efficient. The layered nanoparticle approach reflects a wider push to refine how particle design shapes stability, biodistribution and cellular uptake.

Yet significant questions remain. Results in animal models do not necessarily translate into safe or effective therapies for people. More complex particle structures could complicate large-scale production, and regulators are likely to require extensive data on toxicity, durability and reproducibility. Enhancing interactions with cellular membranes, a strategy intended to promote escape, must also be balanced against the risk of unintended biological effects.

Even so, the study highlights a shift in mRNA research toward deeper engineering of delivery systems. Rather than focusing solely on new genetic payloads, scientists are rethinking how formulation design influences therapeutic performance. Whether core-shell nanoparticles can meet clinical and regulatory standards will determine how much they shape the next phase of mRNA medicine.