Programmed self-assembly of nucleic acid (DNA and RNA) provides a powerful approach for constructing a variety of remarkable nanoscale structures and devices. Because of its self-assembling nature, DNA is an excellent candidate for creating predictable and programmable nanoarchitectures. With the ability to combine designed DNA-branched junctions with sticky-end cohesion, structural DNA nanotechnology (SDN) has developed over the past 30 years. A wide range of multidimensional nanoarchitectures has been constructed, providing all sorts of potential applications.

In this thesis, we first describe the design and self-assembly of complex nanoarchitectures from multiple-stranded DNA motifs. Unpurified strands without perfect stoichiometry were mixed to form finite-sized structures....[ Read more ]

Programmed self-assembly of nucleic acid (DNA and RNA) provides a powerful approach for constructing a variety of remarkable nanoscale structures and devices. Because of its self-assembling nature, DNA is an excellent candidate for creating predictable and programmable nanoarchitectures. With the ability to combine designed DNA-branched junctions with sticky-end cohesion, structural DNA nanotechnology (SDN) has developed over the past 30 years. A wide range of multidimensional nanoarchitectures has been constructed, providing all sorts of potential applications.

In this thesis, we first describe the design and self-assembly of complex nanoarchitectures from multiple-stranded DNA motifs. Unpurified strands without perfect stoichiometry were mixed to form finite-sized structures. By utilizing legacy double crossover (DX) motifs with different domain length designs, we successfully constructed the corresponding 2D arrays, and characterized the structure by atomic force microscopy (AFM). A variety of wire-frame structures with different mesh sizes were also successfully built with three-arm junction, four-arm junction and hexagonal motifs.

Secondly, with a strong interest in the cellular applications of DNA nanoarchitectures, we designed and constructed a DNA-based, pH-responsive nanocarrier system for targeted drug delivery. We used the PSMA A10 RNA aptamer to specifically target human prostate LNCaP cells, and employed i-motif as the pH-responsive unit. The nanocarriers were characterized by a particle size analyzer and scanning electron microscopy (SEM). The in vitro pH-responsive drug release was verified by fluorescence spectroscopy. We also demonstrated the specific targeting ability of the nanocarrier system by anti-proliferation assay, as well as cellular uptake visualized by confocal microscopy.

Finally, we developed a DNA-based nanothermometer that utilized triple fluorescent labeled oligonucleotides. Combining FRET effect and temperature-responsive DNA, this thermometer could measure the temperature increases in living Hela cells. The in vitro and in vivo temperature-responsiveness were confirmed by fluorescence spectrometry and confocal microscopy.