A tumor mRNA-triggered photodynamic molecular beacon based on oligonucleotide hairpin control of singlet oxygen production

Research output: Journal Publications and Reviews (RGC: 21, 22, 62)21_Publication in refereed journal

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Author(s)

  • Juan Chen
  • Jonathan F. Lovell
  • Klara Stefflova
  • Mark Niedre
  • Brian C. Wilson
  • Gang Zheng

Detail(s)

Original languageEnglish
Pages (from-to)775-781
Journal / PublicationPhotochemical and Photobiological Sciences
Volume7
Issue number7
Publication statusPublished - 2008
Externally publishedYes

Abstract

We report a new class of photodynamic molecular beacon (PMB) with tumor specific mRNA-triggered control of singlet oxygen (1O2) production. The beacon contains a single-stranded oligonucleotide linker that forms a stem-loop structure (hairpin) in which the sequence is an antisense oligonucleotide (AS-ON) complementary to a target mRNA. The stem is formed by the annealing of two complementary arm sequences that are on either side of the loop sequence. A photosensitizer molecule (PS) is attached to the end of one arm and a quencher (Q) is similarly attached to the other end. The conformationally-restricted hairpin forces Q to efficiently silence the photoreactivity of PS. In the presence of target mRNA, the hairpin opens and the PS is no longer silenced. Upon irradiating with light, the PS then emits fluorescence and generates cytotoxic 1O2. To show proof of concept, we have synthesized a c-raf-1 mRNA-triggered PMB using pyropheophorbide (Pyro) as PS, carotenoid as Q and c-raf-1 mRNA-targeted AS-ON as the loop sequence. We show that the 1O2 production of Pyro is quenched in its native state by 15-fold and is restored 9-fold by the addition of the target RNA. Comparing this to our recently reported self-folding peptide linker-based PMB, the hairpin effect results in an enhanced 1O2 quenching efficiency that decreases the residual 1O2 production by over 3-fold, thus providing enhanced control of 1O2 production upon target-linker interactions. When incubated with c-raf-1 expressing MDA-MB-231 cancer cells, the PMB displayed efficient cellular uptake and subsequently effective PDT activation in targeted cells. © The Royal Society of Chemistry and Owner Societies.

Citation Format(s)

A tumor mRNA-triggered photodynamic molecular beacon based on oligonucleotide hairpin control of singlet oxygen production. / Chen, Juan; Lovell, Jonathan F.; Lo, Pui-Chi; Stefflova, Klara; Niedre, Mark; Wilson, Brian C.; Zheng, Gang.

In: Photochemical and Photobiological Sciences, Vol. 7, No. 7, 2008, p. 775-781.

Research output: Journal Publications and Reviews (RGC: 21, 22, 62)21_Publication in refereed journal