I know that it is the pivotal driving force for endosomal escape, via "proton-sponge effect", a mechanism explained by the acidification of the endosome or lysosome by "the pumping of protons, accompanied by the influx of chloride ions that compensates the proton influx into the vesicle. This ion influx causes an increase in the osmotic pressure inside the vesicle and thus a swelling process ruptures the endosome/lysosome, allowing the escape of the polyplexes before being degradated"[1].

But why? What does the buffering activity have to do with the acidification / H+ pumping to the intracellular milieu of the cell? Does the polyplex "attract" ions? Why? How?

[1] Agirre, M. et al - Low Molecular Weight Chitosan (LMWC)-based Polyplexes for pDNA Delivery: From Bench to Bedside , Polymers

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