Enhanced gene and siRNA delivery by polycation-modified mesoporous silica nanoparticles loaded with chloroquine

David Oupicky, Shanta Raj Bhattarai, Elayaraja Muthuswamy, Amit Wani, Michal Brichacek, Antonio L. Castañeda, Stephanie L. Brock

Research output: Contribution to journalArticlepeer-review

91 Scopus citations

Abstract

Purpose To prepare mesoporous silica-based delivery systems capable of simultaneous delivery of drugs and nucleic acids. Methods The surface of mesoporous silica nanoparticles (MSN) was modified with poly(ethylene glycol) (PEG) and poly(2-(dimethylamino)ethylmethacrylate) (PDMAEMA) or poly (2-(diethylamino)ethylmethacrylate) (PDEAEMA). The particles were then loaded with a lysosomotropic agent chloroquine (CQ) and complexed with plasmid DNA or siRNA. The ability of the synthesized particles to deliver combinations of CQ and nucleic acids was evaluated using luciferase plasmid DNA and siRNA targeting luciferase and GAPDH. Results The results show a slow partial MSN dissolution to form hollow silica nanoparticles in aqueous solution. The biological studies show that polycation-modified MSN are able to simultaneously deliver CQ with DNA and siRNA. The codelivery of CQ and the nucleic acids leads to a significantly increased transfection and silencing activity of the complexes compared with MSN not loaded with CQ. Conclusion PEGylated MSN modified with polycations are promising delivery vectors for combination drug/nucleic acid therapies.

Original languageEnglish (US)
Pages (from-to)2556-2568
Number of pages13
JournalPharmaceutical Research
Volume27
Issue number12
DOIs
StatePublished - Dec 2010

Keywords

  • Gene delivery
  • Mesoporous
  • Nanoparticles
  • Polycation
  • SiRNA
  • Silica

ASJC Scopus subject areas

  • Biotechnology
  • Molecular Medicine
  • Pharmacology
  • Pharmaceutical Science
  • Organic Chemistry
  • Pharmacology (medical)

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