A prostate cancer-targeted polyarginine-disulfide linked PEI nanocarrier for delivery of microRNA. Issue 2 (1st September 2015)

• Record Type: Journal Article
• Authors: Zhang, Tingting; Xue, Xiang; He, Dalin; Hsieh, Jer-Tsong
• Is Part Of: Cancer letters. Volume 365:Issue 2(2015)
• Page Start: 156
• Page End: 165
• Publication Date: 2015-09-01
• Subjects: MicroRNA -- R11 peptide -- Prostate cancer -- Polyplex; Cancer -- Periodicals; Neoplasms -- Periodicals; Cancer -- Périodiques; Electronic journals; 616.994
• DOI: 10.1016/j.canlet.2015.05.003
• Languages: English
• ISSNs: 0304-3835

Abstract

Highlights: The R11-nanomaterials could specifically deliver miR-145 to prostate cancer. The functional action of miR-145 oligomers can be released from polyplexes. The R11-nanomaterials could dramatically inhibit tumor growth and prolonged survival time. 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.