Co-delivery of proapoptotic peptide and p53 DNA by reduction-sensitive polypeptides for cancer therapy

In order to produce a more efficient cancer cell death, a dual-functional polypeptide, xPolyR8-KLA(TPP), was synthesized by disulfide cross-linking CR8C and C-KLA(TPP). The obtained xPolyR8-KLA(TPP) could not only initiate tumor cell apoptosis by C-KLA(TPP) with improved cell penetrating ability, but was also capable of loading and delivering the tumor cell suppressing p53 gene. It was found that, after internalization by cancer cells, the xPolyR8-KLA(TPP)/p53 complex released the C-KLA(TPP) moiety and the p53 gene in the cytoplasm due to its reducible disulfide bonds. By regulating both the intrinsic and extrinsic apoptotic pathways, the xPolyR8-KLA(TPP)/p53 complex performed as a synergetic system and lead to a more efficient cancer cell death.