Interactions at the Target Cell

The plasma membrane presents cationic polymers with a substantial barrier to successfully gaining entry to the cell, as it is a dynamic and a relatively lipophilic structure that restricts the admittance of large, hydrophilic or charged molecules. The contribution of certain pathways in the uptake of cationic polymer-mediated gene delivery is not well understood it is generally believed that the uptake of polyplexes predominantly oecurs through endocytosis, although multiple mechanisms for endocytosis have been described to date and the current question is which pathway of endocytosis is responsible for cationic polymer uptake. 

The proton sponge effect was first proposed by Behr and co-workers. The proton sponge nature of PEI and other materials, which display relatively high transfection efficiencies, such as lipopolyamines, PAMAM den-drimers and various imidazole-containing polymers, is thought 

Further Interactions with cdiuiar organelles induding mitochorKirial 

It is clear the interrelationships between the molecular characteristics of the cationic polymer and its proton buffering capability are more complicated than one can simplistically deduce from the amine groups found on the polymer. There is currently insufficient data regarding which molecular features govern the proton titratability of cationic polymers to rationally guide the design of new or enhanced polymer materials, which possess improved intracellular trafficking efficiencies. 

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