Date of Award
Doctor of Philosophy (PhD)
Ivan J. Dmochowski
Oligonucleotide-conjugated bio-hybrid nanomaterials with a dense DNA layer on the surface have been shown to possess extraordinary selectivity and sensitivity for DNA detection as well as promising results as delivery agents, as demonstrated with the exceptional example of polyvalent oligonucleotide-conjugated gold nanoparticles. However, progress in this field has been slowed, since achieving high DNA density functionalization on the nanoparticle surface for materials other than gold is a major challenge. In this body of work, we have developed a general system to conjugate a dense layer of DNA on the surface of nanoparticles by the self-assembly of DNA block copolymer. These hybrid nanostructures demonstrated enhanced DNA binding, where the DNA strands on the surface of the nanoparticles can recognize and bind to complementary DNA strands without the addition of salt, a condition where free DNA strands do not form duplex. These assemblies are also selective in DNA recognition; they can distinguish different number base mismatches of the complementary DNA. It was determined that these assemblies possess a surface DNA density that is four times higher than that of DNA-conjugated gold nanoparticles of the same size, the highest DNA functionalization reported in the literature in this size range. These assemblies were also effectively taken up by cells without the use of a co-transfecting agent. The high DNA density also protects the degradation of the DNA, making them ideal candidates for DNA delivery and antisensing applications. Lastly, these assemblies have been tested for their antisensing capability, and found that they can effectively down regulate a targeted protein.
Chen, Xi-Jun, "Multifunctional Nanomaterials of DNA Block Copolymers: Synthesis, Self- Assembly, Thermodynamic Studies and Biomedical Applications" (2013). Publicly Accessible Penn Dissertations. 743.