Show simple item record

dc.contributor.advisor Halas, Naomi J.
dc.creatorHuschka, Ryan
dc.date.accessioned 2013-06-05T15:49:25Z
dc.date.accessioned 2013-06-05T15:49:29Z
dc.date.available 2013-06-05T15:49:25Z
dc.date.available 2013-06-05T15:49:29Z
dc.date.created 2012-12
dc.date.issued 2013-06-05
dc.date.submitted December 2012
dc.identifier.urihttp://hdl.handle.net/1911/71296
dc.description.abstract Plasmon-resonant nanoparticle complexes show promising potential for light-triggered, controllable delivery of deoxyribonucleic acids (DNA) for research and therapeutic purposes. For example, the approach of RNA interference (RNAi) ‒ using antisense DNA or RNA oligonucleotides to silence activity of a specific pathogenic gene transcript and reduce expression of the encoded protein ‒ is very useful in dissecting genetic function and holds promise as a molecular therapeutic. Herein, we investigate the mechanism and probe the in vitro therapeutic potential of DNA light-triggered release from plasmonic nanoparticles. First, we investigate the mechanism of light-triggered release by dehybridizing double-stranded (dsDNA) via laser illumination from two types of nanoparticle substrates: gold (Au) nanoshells and Au nanorods. Both light-triggered and thermally induced releases are distinctly observable from nanoshell-based complexes. Surprisingly, no analogous measurable light-triggered release was observable from nanorod-based complexes below the DNA melting temperature. These results suggest that a nonthermal mechanism may play a role in light-triggered DNA release. Second, we demonstrate the in vitro light-triggered release of molecules non-covalently attached within dsDNA bound to the Au nanoshell surface. DAPI (4',6-diamidino-2-phenylindole), a bright blue fluorescent molecule that binds reversibly to double-stranded DNA, was chosen to visualize this intracellular light-induced release process. Illumination through the cell membrane of the nanoshell-dsDNA-DAPI complexes dehybridizes the DNA and releases the DAPI molecules within living cells. The DAPI molecules diffuse to the nucleus and associate with the cell’s endogenous DNA. This work could have future applications towards drug delivery of molecules that associate with dsDNA. Finally, we demonstrate an engineered Au nanoshell (AuNS)-based therapeutic oligonucleotide delivery vehicle, designed to release its cargo on demand upon illumination with a near-infrared (NIR) laser. A poly(L)lysine peptide (PLL) epilayer coated onto the AuNS surface (AuNS-PLL) is used to capture intact, single-stranded antisense DNA oligonucleotide, or alternatively, double-stranded short-interfering RNA (siRNA) molecules. A green fluorescent protein (GFP)-expressing human lung cancer H1299 cell line was used to determine cellular uptake and GFP gene silencing mediated by AuNS-PLL delivery vector. The light-triggered release of oligonucleotides could have broad applications in the study of cellular processes and in the development of intracellular targeted therapies.
dc.format.mimetype application/pdf
dc.language.iso eng
dc.subjectNanoparticles
Plasmons
Gene therapy
Controlled release
DNA
SiRNA
Nanoshells
Gold nanoshells
Plasmon resonance
Light triggered release
Downregulation
dc.title Light-Triggered Release of DNA from Plasmon-Resonant Nanoparticles
dc.contributor.committeeMember Link, Stephan
dc.contributor.committeeMember Nordlander, Peter J.
dc.contributor.committeeMember Ji, Lin
dc.date.updated 2013-06-05T15:49:30Z
dc.identifier.slug 123456789/ETD-2012-12-247
dc.type.genre Thesis
dc.type.material Text
thesis.degree.department Chemistry
thesis.degree.discipline Natural Sciences
thesis.degree.grantor Rice University
thesis.degree.level Doctoral
thesis.degree.name Doctor of Philosophy
dc.identifier.citation Huschka, Ryan. "Light-Triggered Release of DNA from Plasmon-Resonant Nanoparticles." (2013) PhD diss., Rice University. http://hdl.handle.net/1911/71296.


Files in this item

Thumbnail

This item appears in the following Collection(s)

Show simple item record