Alkyl cross-linked low molecular weight polypropyleneimine dendrimers as efficient gene delivery vectors

Objective(s): First, ۱۰-bromodecanoic acid was covalently attached to all available surface primary amines of PPI G۲ and G۳ to increase their lipophilicity. In the subsequent step, PPIs were conjugated to the alkylcarboxylate groups of alkylcarboxylate-PPI derivatives to increase the number of surface primary amines. Physicochemical properties of modified PPIs were determined. Transfection experiments (using both luciferase and green fluorescent protein (GFP)- expressing plasmids) and cytotoxicity assay were performed to evaluate the efficiency of the final derivatives. Materials and Methods: First, ۱۰-bromodecanoic acid was covalently attached to all available surface primary amines of PPI G۲ and G۳ to increase their lipophilicity. In the subsequent step, PPIs were conjugated to the alkylcarboxylate groups of alkylcarboxylate-PPI derivatives to increase the number of surface primary amines. Physicochemical properties of modified PPIs were determined. Transfection experiments (using both luciferase and green fluorescent protein (GFP)- expressing plasmids) and cytotoxicity assay were performed to evaluate the efficiency of the final derivatives. Results: Fabricated vectors condensed DNA effectively so that polyplexes with appropriate size (below ۱۵۵ nm) and positive surface charge were constructed. Cross-linked low molecular weight PPIs (G۲ or G۳) with decanoate linkage increased transfection efficiency significantly while maintaining the low cytotoxicity. PPI G۲ derivative exhibited increased buffering capacity which is believed to be responsible for better proton sponge mechanism leading to higher transfection efficiency. Conclusion: Our results indicated that oligomerization of low molecular weight PPI (PPI G۲-alkyl-PPI G۲ conjugate) could be an approach to increase the transfection efficiency and to lower the cytotoxicity of low molecular weight polycations.

کلیدواژه ها:

Alkylcarboxylate chains Gene delivery ، Non-viral vectors ، Polypropyleneimine