Light-mediated activation of siRNA release in diblock copolymer assemblies for controlled gene silencing

Abbygail A. Foster, Chad T. Greco, Matthew Green, Thomas H. Epps, Millicent O. Sullivan

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

Controllable release is particularly important for the delivery of small interfering RNA (siRNA), as siRNAs have a high susceptibility to enzymatic degradation if release is premature, yet lack silencing activity if they remain inaccessible within the cytoplasm. To overcome these hurdles, novel and tailorable mPEG-b-poly(5-(3-(amino)propoxy)-2-nitrobenzyl methacrylate) (mPEG-b-P(APNBMA)) diblock copolymers containing light-sensitive o-nitrobenzyl moieties and pendant amines are employed to provide both efficient siRNA binding, via electrostatic and hydrophobic interactions, as well as triggered charge reversal and nucleic acid release. In particular, siRNA/mPEG-b-P(APNBMA)<inf>23.6</inf> polyplexes show minimal aggregation in physiological salt and serum, and enhanced resistance to polyanion-induced unpackaging compared to polyethylenimine preparations. Cellular delivery of siRNA/mPEG-b-P(APNBMA)<inf>23.6</inf> polyplexes reveals greater than 80% cellular transfection, as well as rapid and widespread cytoplasmic distribution. Additionally, UV irradiation indicates ≈70% reduction in targeted gene expression following siRNA/mPEG-b-P(APNBMA)<inf>23.6</inf> polyplex treatment, as compared to 0% reduction in polyplex-treated cells without UV irradiation, and only ≈30% reduction for Lipofectamine-treated cells. The results here highlight the potential of these light-sensitive copolymers with a well-defined on/off switch for applications including cellular patterning for guided cell growth and extension, and cellular microarrays for exploring protein and drug interactions that require enhanced spatiotemporal control of gene activation.

Original languageEnglish (US)
Pages (from-to)760-770
Number of pages11
JournalAdvanced healthcare materials
Volume4
Issue number5
DOIs
StatePublished - Apr 1 2015
Externally publishedYes

Fingerprint

Gene Silencing
RNA
Methacrylates
Small Interfering RNA
Block copolymers
Genes
Chemical activation
Light
Cells
Irradiation
Drug interactions
Polyethyleneimine
Protein Array Analysis
Nucleic acids
Cell growth
Microarrays
Static Electricity
Hydrophobic and Hydrophilic Interactions
Drug Interactions
Gene expression

Keywords

  • Diblock copolymers
  • Photoresponsiveness
  • Polyplexes
  • RNA interference
  • SiRNA

ASJC Scopus subject areas

  • Biomedical Engineering
  • Biomaterials
  • Pharmaceutical Science

Cite this

Light-mediated activation of siRNA release in diblock copolymer assemblies for controlled gene silencing. / Foster, Abbygail A.; Greco, Chad T.; Green, Matthew; Epps, Thomas H.; Sullivan, Millicent O.

In: Advanced healthcare materials, Vol. 4, No. 5, 01.04.2015, p. 760-770.

Research output: Contribution to journalArticle

Foster, Abbygail A. ; Greco, Chad T. ; Green, Matthew ; Epps, Thomas H. ; Sullivan, Millicent O. / Light-mediated activation of siRNA release in diblock copolymer assemblies for controlled gene silencing. In: Advanced healthcare materials. 2015 ; Vol. 4, No. 5. pp. 760-770.
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