Delivery of RIPK4 small interfering RNA for bladder cancer therapy using natural halloysite nanotubes

Sci Adv. 2019 Sep 25;5(9):eaaw6499. doi: 10.1126/sciadv.aaw6499. eCollection 2019 Sep.

Abstract

RNA interference (RNAi) technology can specifically silence the expression of a target gene and has emerged as a promising therapeutic method to treat cancer. In the present study, we showed that natural halloysite nanotube (HNT)-assisted delivery of an active small interfering RNA (siRNA) targeting receptor-interacting protein kinase 4 ( RIPK4 ) efficiently silenced its expression to treat bladder cancer. The HNTs/siRNA complex increased the serum stability of the siRNA, increased its circulation lifetime in blood, and promoted the cellular uptake and tumor accumulation of the siRNA. The siRNA markedly down-regulated RIPK4 expression in bladder cancer cells and bladder tumors, thus inhibiting tumorigenesis and progression in three bladder tumor models (a subcutaneous model, an in situ bladder tumor model, and a lung metastasis model), with no adverse effects. Thus, we revealed a simple but effective method to inhibit bladder cancer using RIPK4 silencing, indicating a promising therapeutic method for bladder cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / genetics
  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • Chemistry Techniques, Synthetic
  • Disease Models, Animal
  • Drug Carriers*
  • Gene Transfer Techniques*
  • Genetic Therapy
  • Humans
  • Lysosomes / metabolism
  • Mice
  • Models, Biological
  • NF-kappaB-Inducing Kinase
  • Nanotubes* / chemistry
  • Nanotubes* / ultrastructure
  • Protein Serine-Threonine Kinases / genetics*
  • Protein Serine-Threonine Kinases / metabolism
  • RNA Interference
  • RNA, Small Interfering / administration & dosage
  • RNA, Small Interfering / chemistry
  • RNA, Small Interfering / genetics*
  • Urinary Bladder Neoplasms / genetics
  • Urinary Bladder Neoplasms / metabolism
  • Urinary Bladder Neoplasms / pathology
  • Urinary Bladder Neoplasms / therapy
  • Xenograft Model Antitumor Assays

Substances

  • Drug Carriers
  • RNA, Small Interfering
  • RIPK4 protein, human
  • Protein Serine-Threonine Kinases