Delivering molecules or drugs into the body has its challenges, especially when you need to get to a specific place that requires the molecule to pass through the liver first. One of the trickier targets is the bone marrow and its cells. A team led by TU Eindhoven has developed a prototype based on apolipoprotein lipid nanoparticles (aNPs) that can carry small interfering RNA (siRNA), among other things. This can be used to deliver nucleic acid-based drugs to the right place.

The researchers were inspired by the natural nanotransport system of lipoproteins, which consist of apolipoproteins and fatty molecules. Lipoproteins interact with many different cell types and naturally transport microRNA molecules. It is therefore ideal to be able to design this type of package and to modify it so that it goes where you want it to go.

After designing more than seventy aNPs, the researchers selected eight different ones to test further in mice. They did this by seeing how well the packaged siRNAs could knock out the gene for the fluorescent protein LAMP1. Two of the aNPs showed widespread silencing in both bone marrow cells (haematopoietic stem cells) and their precursors (myeloid progenitors).

The team then tested whether either aNP could also carry mRNA and antisense oligonucleotides. The packaging worked well for both types of nucleotides, and they were indeed able to deliver mRNA to the bone marrow of mice, where it could actually perform its function.

The authors believe that the aNP platform could be the basis for clinical applications such as immune regulation, vaccination and even gene editing in stem cells for rare inherited diseases.

Hofstraat, S.R.J. et al (2025) Nat. Nanotechnol, DOI: 10.1038/s41565-024-01847-3