Design And Synthesis Of Self-assembled DNA Nanoflowers And Their Applications In Drug Delivery And Bioimaging

Self-assembled DNA nanostructure are well defined nanoscale shape. With features of excellent biocompatibility, uniform scale, DNA nanostructures have a great potential for bimedical applications in such areas as bioimaging, biosensing, and drug delivery.Cancer is one of the main causes of death. Accordingly to World Cancer Report, the number of cancer patients increased by one thousand and four hundred millions in the world in 2012, and eight million patients died of cancer. The limitations of current cancer diagnosis strategies and the lack of effective treatment are the main reasons for such cancer occurrence and high motility. Thus, establishing effective early-stage detection method and cancer treatment strategy have attracted a lot of attention. This thesis will be focused on the synthesis and application of a type of novel DNA nanostructures-- DNA nanoflowers, and the applications in targeted drug delivery to cancer cells and multicolor imaging for cancer cells.Chapter Two will introduce the construction of DNA nanoflowers. DNA nanoflowers are the crystalized product of highly concent rated DNA solution. The synthesis of DNA nanoflowers was achieved via an enzymatic reaction, Rolling Circle Replications, using DNA templates, DNA primers, DNA polymerase, d NTPs, and appropriate buffer solution. This chapter will introduce the systematic s tudy of the factors that influence the construction of DNA nanoflowers, including reaction time, DNA sequences, and DNA polymerase. Moreover, this chapter will study the stability of DNA nanoflowers in complex biosystem and thermal stability.Chapter Three will demonstrate the applications of DNA nanoflowers in targeted anti-cancer drug delivery. We have studied the drug delivery using DNA nanoflowers in both chemosensitive and multi-drug resistant cancer cells. Specifically, we systematically evaluated DNA nanoflowers for their targeted binding specificity, the ability of cell internalization, and the ability to inhibit cell proliferation.Chapter Four will present the applications of multicolor imaging by DNA nanoflowers. By doping fluorescent molecules to DNA nanoflowers, we developed multicolor DNA nanoflowers based on FRET(fluorescence resonance energy transfer). By changing the ratio of different fluorescent dyes, these DNA nanoflowers exhibited various colors with the excitation by one laser.