title: A specific aptamer-cell penetrating peptides complex delivered siRNA efficiently and suppressed prostate tumor growth in vivo.
abstract: Specific and efficient delivery of siRNA into intended tumor cells remains as a challenge, even though RNAi has been exploited as a new strategy for prostate cancer therapy. This work aims to address both specificity and efficiency of SURVIVIN-siRNA delivery by constructing a therapeutic complex using combinatorial strategies. A fusion protein STD was first expressed to serve as a backbone, consisting of streptavidin, a cell-penetrating peptide called Trans-Activator of Transcription (TAT) and a double-stranded RNA binding domain. A biotinylated Prostate Specific Membrane Antigen (PSMA) specific aptamer A10 and SURVIVIN-siRNA were then linked to STD protein to form the therapeutic complex. This complex could specifically targeted PSMA(+) tumor cells. Compared to lipofectamine and A10-siRNA chimera, it demonstrated higher efficiency in delivering siRNA into target cells by 19.2% and 59.9%, and increased apoptosis by 16.8% and 26.1% respectively. Upon systemic administration, this complex also showed significant efficacy in suppressing tumor growth in athymic mice (p <0.001). We conclude that this therapeutic complex could specifically and efficiently deliver SURVIVIN-siRNA to target cells and suppressed tumor growth in vivo, which indicates its potential to be used as a new strategy in prostate cancer therapy.
authors.affiliation: a Department of Clinical Laboratory Medicine , Xijing Hospital, Fourth Military Medical University , Xi'an , China.|b Public Health England Clinical Microbiology & Public Health Laboratory Cambridge, Cambridge University Hospitals NHS Foundation Trust, Addenbrooke's Hospital , UK.
authors.forename: Yanjun
authors.initials: Y
authors.lastname: Diao
authors.affiliation: a Department of Clinical Laboratory Medicine , Xijing Hospital, Fourth Military Medical University , Xi'an , China.
authors.forename: Jiayun
authors.initials: J
authors.lastname: Liu
authors.affiliation: a Department of Clinical Laboratory Medicine , Xijing Hospital, Fourth Military Medical University , Xi'an , China.
authors.forename: Yueyun
authors.initials: Y
authors.lastname: Ma
authors.affiliation: a Department of Clinical Laboratory Medicine , Xijing Hospital, Fourth Military Medical University , Xi'an , China.
authors.forename: Mingquan
authors.initials: M
authors.lastname: Su
authors.affiliation: b Public Health England Clinical Microbiology & Public Health Laboratory Cambridge, Cambridge University Hospitals NHS Foundation Trust, Addenbrooke's Hospital , UK.
authors.forename: Hongyi
authors.initials: H
authors.lastname: Zhang
authors.affiliation: a Department of Clinical Laboratory Medicine , Xijing Hospital, Fourth Military Medical University , Xi'an , China.
authors.forename: Xiaoke
authors.initials: X
authors.lastname: Hao
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D045744:Cell Line, Tumor; D057846:Cell-Penetrating Peptides / Q000378:metabolism*; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology; D034741:RNA, Small Interfering / Q000235:genetics*; D014162:Transfection
chemical_list: D057846:Cell-Penetrating Peptides; D034741:RNA, Small Interfering
keywords: Efficacy; prostate cancer; siRNA delivery; specificity; survivin