An additional issue with current LNP technology is that, only a very small percentage of the cargo, in the case of RNA, actually reaches the cytosol of target cells. One of the biggest hurdles is the cargo endosomal escape. To optimize this crucial process, it is necessary to enhance LNP fusion with the endosome while avoiding excessive fusogenicity with other lipid compartments . Understanding the pH-dependent phase behavior of LNPs is essential for optimizing endosomal escape . Despite several studies that attempt to shed light on the matter, a comprehensive understanding is still lacking due to the multivariate nature of LNPs .