Cell transcytosing poly-arginine coated magnetic nanovector for safe and effective siRNA delivery

Omid Veiseh, Forrest M. Kievit, Hyejung Mok, Joseph Ayesh, Cassra Clark, Chen Fang, Matthew Leung, Hamed Arami, James O. Park, Miqin Zhang

Research output: Contribution to journalArticle

75 Scopus citations

Abstract

Lack of safe and effective carriers for delivery of RNA therapeutics remains a barrier to its broad clinical application. We report the development of a cell tanscytosing magnetic nanovector engineered as an siRNA carrier. Iron oxide nanoparticles were modified with poly(ethylene glycol) (PEG), small interfering RNA (siRNA), and a cationic polymer layer. Three nanovector formulations with cationic polymer coatings of poly-arginine (pArg), polylysine (pLys), and polyethylenimine (PEI), respectively, were prepared. The three nanovector formulations where evaluated for safety and ability to promote gene silencing in three types of cancer cells C6/GFP+, MCF7/GFP+, and TC2/GFP+, mimicking human cancers of the brain, breast, and prostate, respectively. Cell viability and fluorescence quantification assays revealed that pArg-coated nanovectors were most effective in promoting gene knockdown and least toxic of the three nanovector formulations tested. Transmission electron microscopy (TEM) imaging of nanovector treated cells further demonstrated that pArg-coated nanovectors enter cells through cell transcytosis, while pLys and PEI coated nanovectors enter cells endocytosis. Our findings suggest that NPs engineered to exploit the cell transcytosis intracellular trafficking pathway may offer a more safe and efficient route for siRNA delivery.

Original languageEnglish (US)
Pages (from-to)5717-5725
Number of pages9
JournalBiomaterials
Volume32
Issue number24
DOIs
StatePublished - Aug 2011

Keywords

  • Cancer
  • Gene therapy
  • Iron oxide nanoparticle
  • MRI
  • SiRNA
  • Transcytosis

ASJC Scopus subject areas

  • Bioengineering
  • Ceramics and Composites
  • Biophysics
  • Biomaterials
  • Mechanics of Materials

Fingerprint Dive into the research topics of 'Cell transcytosing poly-arginine coated magnetic nanovector for safe and effective siRNA delivery'. Together they form a unique fingerprint.

  • Cite this

    Veiseh, O., Kievit, F. M., Mok, H., Ayesh, J., Clark, C., Fang, C., Leung, M., Arami, H., Park, J. O., & Zhang, M. (2011). Cell transcytosing poly-arginine coated magnetic nanovector for safe and effective siRNA delivery. Biomaterials, 32(24), 5717-5725. https://doi.org/10.1016/j.biomaterials.2011.04.039