Aptamer-conjugated DNA Tetrahedron For The Detection Of Breast Cancer And Target Delivery Of Doxrubincin

Cancer is a serious threat to human health and life. The early detection and diagnosis and to take timely and effective treatment is a key factor in the successful treatment of cancer. Recently, a plenty of molecular probes were developed to achieve the needs of clinical applications. On the other hand, the effective treatment is very important to improve the rate of survivors. Among them, chemotherapy is the most commonly used clinical treatment, but its has many drawbacks such as poor solubility, poor specificity, toxic side effects, multi-drug resistance and so on. Hence, it has great significance to develop nanocarriers to reduce side effects, enhance the therapeutic effect and overcome the multi-drug resistance.Aptamer has attracted lots of interests due to its high specificity and affinity. However, pure aptamer can hardly resist the enzymatic degradation in the complicated physiological environment. Studies have shown that the nanomaterials can protect the degradation of aptamers, and also to provide a platform for multivalent aptamer connection.DNA nanotechnology has draw great attentions in biological testing and drug delivery fields because of its programmability, biocompatibility, and no significant cytotoxicity and immune stimulating. Wherein, DNA tetrahedron has been widely used in the design of drug delivery and biosensors. Many papers have reported to use of DNA tetrahedron to successful delivery CpG, doxorubincin, and small interfering RNA into the cells. Thus, DNA tetrahedron is considered a safe, good biocompatibility, high stability and efficient nanocarrier.The article was composed of three chapters. The research background and significance of the work were elaborated. Methods and results of the experiments were described. The potential application and development of the drug delivery system were also discussed.In chapter one, the damage of cancer and the importance of its diagnose and therapy were reviewed briefly. Secondly, traditional methods of cancer diagnose and therapy were introduced. Thirdly, we described in detail DNA nanotechnology and its applications in cancer diagnose and therapy.In chapter two, a novel fluorescent probe based on aptamer conjugated DNA tetrahedral was used for the detection of breast cancer. This probe can high selectively bind to MUC 1 expressed on MCF-7 cells. At the presence of MUC 1, the conformation of the probe changes, result in a "turn-on" signal. DNA tetrahedral can protect the aptamer probe from degradation of nuclease. The results suggested that this probe achieved sensitive and specific detection of MCF-7 cells, with a limit of 300 cells.In chapter three, we developed an aptamer-DNA tetrahedron for the nuclei-target delivery of anticancer drugs to overcome multidrug resistance. So far, most current nanocarriers are designed to target cells, not nuclei, posing an apparent drawback in these systems. Specifically, free drugs released from the nanocarriers into the cytoplasm are re-exposed to the efflux pump, partially reducing therapeutic efficacy. To address that problem, we conjugated AS 1411 aptamer to delivery the anticancer drug doxorubicin to the cell nuclei directly, and in that way overcome the multidrug resistance of cancer cells.