Exploring polyethylenimine‐mediated DNA transfection and the proton sponge hypothesis

By Akin Akinc, Mini Thomas, Alexander M. Klibanov, Robert Langer. Journal of Gene Medicine, 2005

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Magnetic nanoparticles for gene and drug delivery (2008, positive): “In addition, PEI facilitates lysosomal release of the complex following internalisation by buffering the intralysosomal pH causing the lysosome to rupture and release it’s contents (Akinc et al 2005).”
Brief update on endocytosis of nanomedicines (2019, background): “While PLL was able to encapsulate nucleic acids, it failed to deliver nucleic acids efficiently due to aggregation and it inability to avoid lysosomes [110,116].”
Nonviral Gene Delivery: Principle, Limitations, and Recent Progress (2009, positive): “The nonprotonated amines in the PEI exert the so-called proton sponge effect, which effectively stops the acidification of the endosomal pH by neutralizing the protons that are pumped by an active membrane transporter, ATPase (6,84).”
Cationic polystyrene nanosphere toxicity depends on cell-specific endocytic and mitochondrial injury pathways. (2008, background): “Moreover, it is known that many of these non-viral transfection systems can induce cellular toxicity and apoptosis based on their cationic charge and interference in proton pump activities.(13,15,38) It has also been reported with polyplexes prepared from the cationic polymer, polyethyleneimine, tha”