title: A prostate cancer-targeted polyarginine-disulfide linked PEI nanocarrier for delivery of microRNA.
abstract: Recent advances in efficient microRNA (miRNA) delivery techniques using prostate cancer-targeted nanoparticles offer critical information for understanding the functional role of miRNAs in vivo, and for supporting targeted gene therapy in terms of treating miRNA-associated prostate cancer. Here, we report the polyarginine peptide (R11)-labeled non-toxic SSPEI nanomaterials capable of prostate cancer-specific miR-145 delivery to prostate cancer in vivo where they display full bioactivity at completely nontoxic concentrations. The R11-labeled BPEI-SS (R11-SSPEI) nanocarrier showed less toxicity in prostate cancer, and electrostatic interaction of R11-SSPEI with miR-145 exhibited optimal transfection efficacy. The R11-SSPEI/miR-145 polymer could be specifically uptaken in prostate cancer using FAM-miR-145 mixed with R11-SSPEI. The functional action of miR-145 oligomers released from polyplexes was evaluated by a reporter vector containing a miR-145-binding sequence, and showed a significantly reduced reporter signal in a dose-dependent manner. More importantly, in a peritoneal mouse tumor model, the systemic administration of the R11-SSPEI/FAM-miR-145 complex leads to the delivery of miR-145 into the tumors, dramatically inhibiting tumor growth and prolonged survival time. Hence, we establish a novel and prostate cancer-specific targeting system for the systemic in vivo application of microRNAs through R11-SSPEI complexation as a powerful tool for future therapeutic use.
authors.affiliation: Department of Gynecology, The Second Affiliated Hospital of Medical College of Xi'an Jiaotong University, Xi'an, China; Oncology Research Lab, Key Laboratory of Environment and Genes Related to Diseases, Ministry of Education, Xi'an, China. Electronic address: surgenzhang@163.com.
authors.forename: Tingting
authors.initials: T
authors.lastname: Zhang
authors.affiliation: Department of Gynecology, The Second Affiliated Hospital of Medical College of Xi'an Jiaotong University, Xi'an, China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Xue
authors.affiliation: Oncology Research Lab, Key Laboratory of Environment and Genes Related to Diseases, Ministry of Education, Xi'an, China; Department of Urology, The First Affiliated Hospital of Medical College of Xi'an Jiaotong University, Xi'an, China.
authors.forename: Dalin
authors.initials: D
authors.lastname: He
authors.affiliation: Department of Urology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
authors.forename: Jer-Tsong
authors.initials: JT
authors.lastname: Hsieh
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000235:genetics; D045744:Cell Line, Tumor; D004337:Drug Carriers / Q000627:therapeutic use*; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D006801:Humans; D008297:Male; D051379:Mice; D035683:MicroRNAs / Q000235:genetics / Q000627:therapeutic use*; D053758:Nanoparticles / Q000627:therapeutic use; D010455:Peptides / Q000627:therapeutic use; D010534:Peritoneal Neoplasms / Q000188:drug therapy*; D011471:Prostatic Neoplasms / Q000188:drug therapy*; D014162:Transfection
chemical_list: D014408:Biomarkers, Tumor; D004337:Drug Carriers; C541010:MIRN145 microRNA, human; D035683:MicroRNAs; D010455:Peptides; C015462:polyarginine
keywords: MicroRNA; Polyplex; Prostate cancer; R11 peptide