Gene Carrier Showing All-or-None Response to Cancer Cell Signaling

In this work we designed a novel nano carrier, a linear polyethylenimine (LPEI)-peptide conjugate, for cancer-specific expression of transgenes. The conjugate was easily synthesized by using a click chemistry scheme orthogonal to the reactive side groups of the peptide, which is the substrate of protein kinase C alpha (PKC alpha). Polyplexes of the conjugates with plasmid DNA (pDNA) were intact and stably dispersed even in the presence of cell lysate. Despite this stability, the polyplexes readily dissociated upon phosphorylation of the grafted peptides by PKC alpha. Because of its endosomal escape ability and adequate susceptibility to PKC alpha, the polyplexes showed an all-or-none type response to PKC alpha activity in transgene expression in vitro. The polyplexes achieved cancer tissue-specific transgene expression even for a tumor with a relatively low PKC alpha activity. Thus the LPEI-peptide conjugate has high potential as a nanocarrier for cancer-targeted gene therapy.