TARGETED DELIVERY DNA-TETRAHEDRON ASSEMBLED THERAPEUTICS

As advanced as we have become with current cancer therapeutics, there are still challenges that need to be addressed. One of them is the non-specific killing of normal cells in addition to cancerous cells in certain cancer therapies. Ideal cancer therapeutics should be targeted specifically toward tumor cells. Due to the robust self-assembly and versatile addressability of DNA-nanostructures, we explore a DNA tetrahedron nanostructure as a drug carrier. The nanostructure can be decorated with various molecules to either increase immunogenicity, toxicity, or affinity to a specific cell type. The efficiency of the specific binding and internalization of the chosen molecules are measured via flow cytometry. After determining the optimum molecule or combination of molecules to assemble onto the structure for targeting specificity, the delivery capabilities will be evaluated. The drug doxorubicin will be used to load the DNA-nanostructure and attempt to inhibit cancer cell growth. We have found that adding a certain antibody to the DNA-nanostructure appeared to provide specific binding to a B cell mouse lymphoma line and facilitated cellular internalization. We have also found that the presence of CpG seems to aid in the binding of nanostructures decorated with other molecules, as compared to nanostructures with no CpG. Internalization was observed to have a similar trend amongst nanostructures with and without CpG. Currently we are testing a G-quadruplex aptamer and its specific binding efficiency. The feasibility of this therapeutic strategy will be further tested in vivo in tumor-bearing mice. Our DNA-nanostructure has the benefit of being self-assembled and customizable. We have shown that we can bind to and internalize into a cancer cell line. The next steps are to test the drug-loading and unloading capabilities of our structure, and to compare the uptake of drugs delivered via our nanostructure compared to that of free drugs.