Cyclodextrin and polyethylenimine functionalized mesoporous silica nanoparticles for delivery of siRNA cancer therapeutics

Jianliang Shen, Han Cheon Kim, Hua Su, Feng Wang, Joy Wolfram, Dickson Kirui, Junhua Mai, Chaofeng Mu, Liang Nian Ji, Zong Wan Mao, Haifa Shen

Research output: Contribution to journalArticle

123 Scopus citations

Abstract

Effective delivery holds the key to successful in vivo application of therapeutic small interfering RNA (siRNA). In this work, we have developed a universal siRNA carrier consisting of a mesoporous silica nanoparticle (MSNP) functionalized with cyclodextrin-grafted polyethylenimine (CP). CP provides positive charge for loading of siRNA through electrostatic interaction and enables effective endosomal escape of siRNA. Using intravital microscopy we were able to monitor tumor enrichment of CP-MSNP/siRNA particles in live mice bearing orthotopic MDA-MB-231 xenograft tumors. CP-MSNP delivery of siRNA targeting the M2 isoform of the glycolytic enzyme pyruvate kinase (PKM2) resulted in effective knockdown of gene expression in vitro and in vivo. Suppression of PKM2 led to inhibition of tumor cell growth, invasion, and migration.

Original languageEnglish (US)
Pages (from-to)487-497
Number of pages11
JournalTheranostics
Volume4
Issue number5
DOIs
StatePublished - 2014

Keywords

  • Cancer therapy
  • Delivery
  • Gene silencing
  • Mesoporous silica nanoparticle
  • siRNA

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Pharmacology, Toxicology and Pharmaceutics (miscellaneous)

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    Shen, J., Kim, H. C., Su, H., Wang, F., Wolfram, J., Kirui, D., Mai, J., Mu, C., Ji, L. N., Mao, Z. W., & Shen, H. (2014). Cyclodextrin and polyethylenimine functionalized mesoporous silica nanoparticles for delivery of siRNA cancer therapeutics. Theranostics, 4(5), 487-497. https://doi.org/10.7150/thno.8263