Dissertation/Thesis Abstract

Development of Dual Functional DNA/RNA Nanostructures for Drug Delivery
by Valsangkar, Vibhav A., Ph.D., State University of New York at Albany, 2020, 121; 27964522
Abstract (Summary)

In addition to the traditional biochemical functions, DNA and RNA have been increasingly studied as building blocks for the formation of various 2D and 3D nanostructures. DNA has emerged as a versatile building block for programmable self-assembly. DNA-based nanostructures have been widely applied in biosensing, bioimaging, drug delivery, molecular computation and macromolecular scaffolding. A variety of strategies have been developed to functionalize these nanostructures. The major advantage is that DNA is a very stable molecule and its base-pairing properties can be easily utilized to control and program the formation of desired nanostructures. In addition, some of these DNA/RNA nanostructures have been shown to have special properties in targeting cancer cells. In this project, we have utilized 2D and 3D DNA/RNA nanostructures as the platform to demonstrate a facile “Click” strategy to incorporate functional ligands into these nanostructures. Specifically, the DNA three-point star tile (3PST), RNA three-way junction (3WJ) and DNA tetrahedron (TET) are selected as the targets. Using solid-phase oligonucleotide synthesis, we incorporated the desired modifications into the respective nanostructures. The DNA/RNA strands, with various lengths and sequences, could be annealed in specific ratios to generate homogeneous nano complexes from a couple of hours (3WJ) to maximum 48 hours (TET). We modified the DNA/RNA with 2′-O-propargyl groups and observed the formation of the desired nanostructure post functionalization through the modifications. The addition of an azido-modified metal chelating ligand or fluorescent tag as well did not affect the assembly formation. Such modified complexes have great potentials to be used as general delivery platforms for metals or drugs. We further demonstrate proof-of-concept dual functionality nucleic acid nanostructures, where we use click chemistry for the payload attachment on the nanostructures and use light as a trigger to release an attached moiety. For controlled release, we incorporated a photocleavable linker in the strands that can be activated by UV. We confirmed the dual functionality and the viability of this strategy for the application of drug delivery on nucleic acid nanostructures of different size and materials, from simple junctions up to complex assemblies.

Indexing (document details)
Advisor: Sheng, Jia
Commitee: Halvorsen, Ken, Pande, Jayanti, Royzen, Maksim, Yigit, Mehmet
School: State University of New York at Albany
Department: Chemistry
School Location: United States -- New York
Source: DAI-B 81/12(E), Dissertation Abstracts International
Subjects: Chemistry, Biochemistry, Nanotechnology, Medicine
Keywords: DNA nanotechnology, Drug delivery, Nanotechnology, Nucleic acid chemistry, Nucleic acid modifications, RNA nanotechnology
Publication Number: 27964522
ISBN: 9798635281130
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