Highly potent double pH-responsive mRNA carriers were developed combining the polar cationizable succinoyl tetraethylene pentamine (Stp) artificial amino acid motif with apolar protonatable lipoamino fatty acid (LAF) domains. LAF units contain tertiary amines to induce a switch in polarity and conformational changes at endosomal pH. Different spatial arrangements (U-shape or bundle topologies) require distinct polar/apolar ratios. To further fine-tune this balance, two different strategies for hydrophobic modification of the Stp motif were applied. Either the succinoyl linker was replaced by dicarboxylic acids with bulky hydrophobic moieties, or the number of secondary amines was reduced. Thus, a library of U-shape and bundle structures with polar/apolar domain ratios of 1:2, 2:4 or 1:4 was synthesized and formulated as mRNA polyplexes. With carriers containing hydrophobically modified dicarboxylic acids, stable polyplex formation was achieved. For structures with reduced number of secondary amines, particle formation was more challenging. Strongest tunability was shown for U-shapes with higher ratios of the polar domain (1:2). In N2a, J774A.1 and DC2.4 cells, in comparison to previous top performers an up to ~10-fold further increase in luciferase transfection efficiency could be achieved with a cyclohexan-1,2-dicarboxylic acid linker. Furthermore, an increase in cell viability was detected in J774A.1 cells upon reduction of secondary amines. In contrast, structures with higher proportion of the apolar domain (2:4 and 1:4) were less affected by hydrophobic fine-tuning. Further investigation of octanol/water distribution (logD), lytic potential and performance in different cell lines will elucidate details of underlying mechanisms and reveal additional structure activity relations.