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Multifunctional Nanoparticles for Bio-analytical Applications and Therapeutic Delivery

Deodhar, Tejal Jayant

Abstract Details

2013, Doctor of Philosophy, University of Akron, Chemistry.
This dissertation describes the design, synthesis and applications of nanoparticles for bio-analytical assays and for drug/ gene delivery purposes. A new oligonucleotide attached tridentate molecular surface anchor was synthesized using phosphoramidite chemistry. The surface anchor, which consists of the 2,4,9-trithiaadamantane ring as the base, was synthesized by a multistep synthetic procedure, using phosphorous pentasulfide suspended on basic alumina, as the thionation agent. The methyl ester group at the seventh position of the molecule (7-substituted-2,4,9-trithiaadamantane) was converted to a hexanol group, which was further converted to a phosphoramidite end group. Specific oligonucleotide sequences were synthesized using a solid phase DNA synthesizer, during which the tripodal surface anchor, modified with phosphoramidite end group was added as the last base. These oligonucleotide attached tripodal molecular surface anchors, were used to functionalize gold nanoparticles to form stable DNA capped nanoparticle probes. On the basis of the distance dependent surface plasmon absorbance exhibited by gold nanoparticles, these probes were used in a colorimetric assay to detect target oligonucleotides in solution. UV-vis spectroscopy, transmission electron microscopy (TEM) and surface plasmon resonance spectroscopy (SPR) were used to characterize the oligonucleotide detection assay and differentiate between complementary, non-complementary and 1-base pair mismatch targets. These novel, oligonucleotide attached, tridentate sulfur ligands show a promising approach towards the development of stable oligonucleotide functionalized gold nanoparticles, than the current anchors used, while exhibiting similar hybridization properties. The concept of formation of supramolecular assemblies was further used for the fabrication and synthesis of a novel photo cleavable polymer nanocapsule, serving as a potential in vivo therapeutic delivery agent. A novel difunctional photo cleavable crosslinker, having photo cleavable sites at defined locations, was synthesized and incorporated within a core shell polymer matrix, by an inverse emulsion radical polymerization reaction. The resulting nanocapsules comprise of a hydrophobic shell poly(tert-butyl acrylate), a hydrophilic interior poly(allylamine) and photo cleavable sites (within the crosslinker). The photo cleavage of the polymer nanocapsules was followed by using infrared spectroscopy as a function of time. In order to test the ability of the nanocarriers to encapsulate therapeutic molecules, green fluorescence protein gene containing plasmid was loaded in the hydrophilic interior, based on the ionic interactions between negatively charged DNA and the free quaternary amino groups of poly(allylamine). In vivo studies for testing toxicity and gene expression ability of the nanocarriers were carried out by using zebra fish as a model organism. The advantage of using this novel nanocapsule for therapeutic delivery is that it can serve as a potential trigger to allow controlled and efficient release of therapeutic molecules into cells. The photo open trigger should allow the nanocapsules to be selectively photo cleaved and release guest molecules within specific cells, resulting in targeted therapeutic delivery.
Yi Pang, Dr. (Advisor)
Michael Taschner, Dr. (Committee Member)
Claire Tessier, Dr. (Committee Member)
Sailaja Paruchuri, Dr. (Committee Member)
Qin Liu, Dr. (Committee Member)
201 p.

Recommended Citations

Citations

  • Deodhar, T. J. (2013). Multifunctional Nanoparticles for Bio-analytical Applications and Therapeutic Delivery [Doctoral dissertation, University of Akron]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=akron1367242624

    APA Style (7th edition)

  • Deodhar, Tejal. Multifunctional Nanoparticles for Bio-analytical Applications and Therapeutic Delivery. 2013. University of Akron, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=akron1367242624.

    MLA Style (8th edition)

  • Deodhar, Tejal. "Multifunctional Nanoparticles for Bio-analytical Applications and Therapeutic Delivery." Doctoral dissertation, University of Akron, 2013. http://rave.ohiolink.edu/etdc/view?acc_num=akron1367242624

    Chicago Manual of Style (17th edition)