This study aimed to investigate the connection between PEI modification, internal DNA packing structure, and pH response of the resultant PEI-based polyplexes. We modified commercially available 25-kDa branched PEI (bPEI) using either acetic anhydride or succinic anhydride to synthesize a range of acetylated PEI (acPEI, 10-50%) and succinylated, or zwitterion-like, PEI (zPEI, 2-40%) polymers, following reaction schemes (Figure ) adapted from previous work.