Li et al. show that putting gold nanoparticles inside of LNPs causes marked improvements in endosomal escape efficiency, describe a likely mechanism, and test their complexes with two therapeutic contexts in mice. A simple innovation which could greatly enhance LNP delivery!

Lipid Nanoparticles (LNPs) effectively deliver mRNA to cells but suffer have low levels of endosomal release. Here the authors report on core-shell LNPs with ionizable lipid–coated gold nanoparticle cores with enhanced pH-responsive membrane disruption, endosomal escape, and cytosolic mRNA delivery improving therapeutic efficiency.