DescriptionBiological systems have evolved complex macromolecular nanostructures to carry out cellular functions with high specificity and efficiency, such as mitochondrial electron transport chains, polymerase and transcription cofactors and light-harvesting antenna in photosynthesis. These organized nanostructures are formed inside cells by spontaneous self-assembly of individual molecular components. In the past few decades, researchers have taken advantage of the self-assembly of nucleic acids to construct various 1D – 3D nanostructures. Self-assembled DNA nanostructures have an inherent advantage of generating programmable nanostructures with controllable parameters of dimension, structural hierarchy and nanometer precision, which can be used for mediating drug release. In this thesis, we have studied single- or double-stranded DNA molecules for forming nanoparticles with minocycline (MH) in the presence of magnesium ions (bridging effect) and π-π stacking interaction. We evaluated multi-dimensional DNA nanostructures (e.g. ssDNA, dsDNA, DNA origami) to load and release MH with sufficient dose during an interval of two weeks. The entrapment efficiency of MH and iii DNA was found to depend on the Mg2+ concentration, DNA length, and types of DNA (i.e. as a function of nitrogen bases). The molecule ssDNA with length > 11-nucleotide (nt) was found to form aggregates with MH in the presence of Mg2+. The titration of Mg2+ concentration showed that the maximum particle formation yield was reached at ~ 4 mM. ssDNA also showed higher dimensional aggregate formation yield than dsDNA, due to the flexible structure of ssDNA allowing more aggregation with MH and Mg2+. In collaboration with Drexel University, we have applied DNA-Mg2+-MH particles to agarose gel encapsulation and release for maintaining the activity of MH during a long period release. This DNA-mediated MH release could be potentially used in the future spinal cord therapy for localized delivery of MH at the injury site.