Guanidinoamidized linear polyethyleneimine for gene delivery

Polycation-Mediated Transfection: Mechanisms of Internalization and Intracellular Trafficking

“…Filipin also disrupts the linkages between the membrane and actin (hence disrupts macropinocytosis, as well as caveolae) . Both reduce TE, ,,, in a dose-dependent manner where measured . Moderate reductions in attachment are observed and are associated with large reductions in TE. ,,,,, There are a few reports where filipin has little effect. ,, An explanation for these effects with regards to syndecans was found by Payne and co-workers, who found that the removal of cholesterol by these agents prevented movement along the cell surface, and hence inhibited the clustering of polyplex-adherent syndecans (see section ).…”

“…Lack of gene expression is often correlated with the onset of chlorpromazine induced toxicity and varies by polycation, cell-line, and even buffer . Chlorpromazine often has no effect on internalization or TE − or moderately decreases internalization but has no effect or increases TE. − In other studies, it can be shown that chlorpromazine knocks down transfection in a dose-responsive manner, ,− but at high concentrations, both internalization and TE are decreased. , …”

Synthesis and characterization of fourth generation polyester‐based dendrimers with cationic amino acids‐modified crown as promising water soluble biomedical devices

“…Hence, the interest in decorating dendrimer scaffolds also with DMG and MG, never used by us to prepare hetero dendrimers, alongside L‐lysine and L‐arginine was born. If lysine and arginine contribute to provide three types of primary amine groups which favor electrostatic interactions and to supply the guanidine group whose importance is well known, the addition of DM and DMG would have improved the buffer capacity and consequently the transfection efficiency.…”

“…L‐histidine, but above all, L‐arginine appear particularly appealing to functionalize synthetic vectors. The guanidine residue of L‐arginine, when it was introduced into low molecular weight linear polyethyleneimine, dramatically reduced low molecular weight linear polyethyleneimine's toxicity, enhanced its DNA‐packaging capability, cellular uptake, and therefore transfection . Furthermore, a recent work described some representative applications also of D‐amino acids in biomedicine and reported as the stereochemistry inversion of amino acids can influence the geometry, spatial arrangement, resistance, and performance of D‐peptides when used for making peptide hydrogels, drug delivery systems, and protein inhibitors.…”

Synthesis and characterization of versatile amphiphilic dendrimers peripherally decorated with positively charged amino acids

“…The diversity of amino acid residues can be exploited to modulate the buffer capacity of the vector and facilitate its escape from endosomal acidic compartments through membrane disruption of endosomes . Together with l ‐histidine, l ‐arginine is particularly appealing for the functionalization of synthetic vectors for many reasons, among which the presence of the guanidine residue in its structure that, as was observed, when introduced into low‐molecular‐weight linear PEI resulted in the ability to markedly reduce linear PEI toxicity and enhance DNA‐packaging capability, cellular uptake and therefore transfection . One of our recent papers described the preparation of seven biodegradable and non‐cytotoxic polyester‐based hydrophilic arginine dendrimers of fourth and fifth generation.…”