Figure 6.

The optimal HK carrier (linear vs. branched) is dependent on the endocytic pH of cells. Upper Panel. At pH 6.5 in the endosomes of transformed and malignant cells, unpacking from the ternary complex (liposome, HK peptide, plasmid) occurs with the release of both linear and branched HK peptides from plasmid DNA. The branched HK peptide with the higher positive charge per molecule than the linear HK results in greater lysis and transfection. Lower Panel. At pH 5.0 in the endosomes of primary cell lines, unpacking occurs, but the branched peptide with an increased charge has a higher affinity toward DNA and is not released (or at least poorly released). In contrast, the highly protonated linear HK (with lower DNA affinity than the branched HK) is released from the plasmid DNA, enabling greater endosomal lysis and transfection.