Figure 15.

Trafficking of oligonucleotide conjugates containing pH-sensitive linker via endocytosis. The conjugates are internalized into the endosomal pathway by gymnotic uptake or by receptor-mediated uptake. pH-sensitive linkers are relatively stable in extracellular matrix at pH 7.4 and labile in endosomal compartments at pH 5.5–6.5. They can selectively release the oligonucleotide in endosomes and hence, can potentially enhance the endosomal escape of oligonucleotides. Created with BioRender.com, JQ25FK563G.