Intracellular nucleic acid delivery via pH-responsive ionizable lipid-mediated endosomal escape

This target refers to the mechanism by which nucleic acids (such as mRNA, siRNA, or DNA) are delivered into the cytoplasm of cells using lipid nanoparticles (LNPs) that contain pH-responsive ionizable lipids. The key challenge in this process is overcoming endosomal entrapment: after cellular uptake by endocytosis, LNPs are sequestered within endosomes. Efficient delivery requires these particles to escape from the endosome before degradation occurs in lysosomes. The mechanism involves pH-dependent protonation of ionizable lipids, leading to membrane interactions, phase transitions, and ultimately endosomal disruption and release of the nucleic acid payload.

Other names

LNP-mediated endosomal escapepH-responsive lipid nanoparticle deliveryIonizable lipid mediated nucleic acid deliveryEndosomal escape of nucleic acids

Protonation of ionizable lipids in the acidic environment of endosomes leads to membrane disruption and release of encapsulated nucleic acids into the cytoplasm.