title: Co-delivery of proapoptotic peptide and p53 DNA by reduction-sensitive polypeptides for cancer therapy.
abstract: 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.
authors.affiliation: Key Laboratory of Biomedical Polymers of Ministry of Education & Department of Chemistry, Wuhan University, Wuhan 430072, PR China. xz-zhang@whu.edu.cn.
authors.forename: Si
authors.initials: S
authors.lastname: Chen
authors.forename: Lei
authors.initials: L
authors.lastname: Rong
authors.forename: Hui-Zhen
authors.initials: HZ
authors.lastname: Jia
authors.forename: Si-Yong
authors.initials: SY
authors.lastname: Qin
authors.forename: Xuan
authors.initials: X
authors.lastname: Zeng
authors.forename: Ren-Xi
authors.initials: RX
authors.lastname: Zhuo
authors.forename: Xian-Zheng
authors.initials: XZ
authors.lastname: Zhang
mesh_terms: D017209:Apoptosis; D045744:Cell Line, Tumor; D057846:Cell-Penetrating Peptides / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D004247:DNA / Q000737:chemistry* / Q000378:metabolism; D004220:Disulfides / Q000737:chemistry* / Q000378:metabolism; D016158:Genes, p53 / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D008928:Mitochondria / Q000737:chemistry* / Q000378:metabolism; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism
chemical_list: D057846:Cell-Penetrating Peptides; D004220:Disulfides; D010455:Peptides; C000611578:xPolyR8-KLA(TPP); D004247:DNA