Fig. 3. Use of ionizable cationic lipids provides an escape from the endosomes and they release the cargo in the cytosolic area, thereby protecting the gene from neutralization/degradation in the endosomal pathway.215 The intracellular trafficking demystifies the pathway that ultimately leads to higher transfection efficiency with less toxicity. (A) High-resolution confocal images showing cy5 mRNA encapsulating LNPs in the endosomal pathway. (B) The correlation between efficiently transfected LNPs and the endocytosis pathway. Rab11, EEA1, and APPL1 have a positive correlation with transfection efficiency of LNPs, while LBPA and LAMP1 have a negative correlation. Other endosomes do not have a correlation. (C) The scheme of the LNP's endocytosis pathway to explain the fact that efficient LNPs go to specific endosomes. Reproduced from (Paramasivam et al. 2021) with permission from J. Cell Biol.215.
