Sweet Vector for Gene Delivery: the Sugar Decoration of Polyplexes Reduces Cytotoxicity with a Balanced Effect on Gene Expression

The use of sugar‐functionalized polyplexes as a nonviral gene delivery vector with lower cytotoxicity than the well‐known polymeric carrier branched polyethyleneimine (BPEI) is investigated. The substitution of primary amine groups in the BPEI chains with lactose residues leads to larger polyplexes, presumably due to the higher amount of polymer required to complete DNA condensation. Nevertheless, the sugar functionalization substantially reduces the cytotoxicity of the assemblies. The nanocomplexes are taken up by the cells to a greater extent, whereas the levels of gene expression are maintained compared to those obtained using BPEI, which is known for its excellent transfection efficiency. Accordingly, the preparation of lower‐cytotoxicity polyplexes while maintaining gene expression, which is highly relevant to the field, is demonstrated. The substitution of primary amine groups in branched polyethyleneimine chains by lactose residues enables the preparation of lower‐cytotoxicity polyplexes that are taken up by cells to a greater extent while maintaining the levels of gene expression.