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 journalArticle

86 Citations (Scopus)

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 - Jan 1 2010

Fingerprint

Chloroquine
Silicon Dioxide
Nanoparticles
Small Interfering RNA
Genes
Nucleic Acids
Luciferases
Polyethylene glycols
DNA
Plasmids
Ethylene Glycol
Drug Combinations
polycations
Transfection
Dissolution
Pharmaceutical Preparations

Keywords

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

ASJC Scopus subject areas

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

Cite this

Oupicky, D., Bhattarai, S. R., Muthuswamy, E., Wani, A., Brichacek, M., Castañeda, A. L., & Brock, S. L. (2010). Enhanced gene and siRNA delivery by polycation-modified mesoporous silica nanoparticles loaded with chloroquine. Pharmaceutical Research, 27(12), 2556-2568. https://doi.org/10.1007/s11095-010-0245-0

Enhanced gene and siRNA delivery by polycation-modified mesoporous silica nanoparticles loaded with chloroquine. / Oupicky, David; Bhattarai, Shanta Raj; Muthuswamy, Elayaraja; Wani, Amit; Brichacek, Michal; Castañeda, Antonio L.; Brock, Stephanie L.

In: Pharmaceutical Research, Vol. 27, No. 12, 01.01.2010, p. 2556-2568.

Research output: Contribution to journalArticle

Oupicky, D, Bhattarai, SR, Muthuswamy, E, Wani, A, Brichacek, M, Castañeda, AL & Brock, SL 2010, 'Enhanced gene and siRNA delivery by polycation-modified mesoporous silica nanoparticles loaded with chloroquine', Pharmaceutical Research, vol. 27, no. 12, pp. 2556-2568. https://doi.org/10.1007/s11095-010-0245-0
Oupicky, David ; Bhattarai, Shanta Raj ; Muthuswamy, Elayaraja ; Wani, Amit ; Brichacek, Michal ; Castañeda, Antonio L. ; Brock, Stephanie L. / Enhanced gene and siRNA delivery by polycation-modified mesoporous silica nanoparticles loaded with chloroquine. In: Pharmaceutical Research. 2010 ; Vol. 27, No. 12. pp. 2556-2568.
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