A prostate cancer-targeted polyarginine-disulfide linked PEI nanocarrier for delivery of microRNA

Tingting Zhang, Xiang Xue, Dalin He, Jer Tsong Hsieh

Research output: Contribution to journalArticle

35 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)156-165
Number of pages10
JournalCancer Letters
Volume365
Issue number2
DOIs
StatePublished - Sep 1 2015

Keywords

  • MicroRNA
  • Polyplex
  • Prostate cancer
  • R11 peptide

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Fingerprint Dive into the research topics of 'A prostate cancer-targeted polyarginine-disulfide linked PEI nanocarrier for delivery of microRNA'. Together they form a unique fingerprint.

  • Cite this