“…Throughout the maturation of the endosomes, the pH decreases from physiological pH 7.4 to pH≈6.5 in the early endosome, pH≈6.0 in the late endosome and pH≈5.0 in the lysosome due to the activity of membrane‐bound ATPase pumps (proton pumps), which pump protons across the endosome and lysosome membrane into the vesicle interior through ATP hydrolysis [234] . The presence of cationic polymers, such as PEI, [91, 142, 144, 147, 152, 235] polyamidoamine, [151] succinyl tetraethylene pentamine, [164] spermine, [89, 139–141, 161, 162, 236] and imidazole‐containing molecules, such as histidine, [83, 90] can all lead to endosomal rupture via the “proton‐sponge” effect. This effect is associated to the large buffering ability of these molecules due to proton binding, which leads to more protons being pumped.…”