Genomic DNA functionalized 3D printed architected materials for drug capture

Abstract

Since the discovery of chemotherapy in the beginning of the 20th century, researchers around the world have been actively developing new and more effective chemotherapeutic agents to better treat cancer. Traditionally, chemotherapeutic agents work by interfering with cell division. However, by virtue of their mechanism of action, healthy normal cells can also be targeted and destroyed. As a result, while chemotherapy is an effective way of managing cancer, the resulting side effects limits its use. One approach currently taken to reduce these side effects is to deliver the chemotherapy drugs directly to the tumor via transarterial chemoembolization, or other similar procedures. While this has been effective in reducing systemic toxicity, more can be done to improve this. Ideally, a device that could sequester any unreacted chemotherapy agents could be installed "downstream" of the tumor prior to them entering systemic circulation. Such drug-capture materials have yet to be realized due to the difficulty in achieving materials that have the right surface chem. and geometry for blood flow. Here, we report the fabrication of DNA functionalized 3D printed porous materials that can be used to capture doxorubicin, a commonly used DNA-targeting chemotherapy agent. We discuss the concept behind the device, the use of 3D printed materials as an ideal substrate, and the chemistries considered in drug binding. To achieve scalability of these devices, we developed a method of functionalizing the surface with cheaply available genomic DNA to these materials, a departure from commonly used synthetic DNA. We characterize the surface of the structure and verify the binding of DNA to the surface via XPS, EDS and the use of chem. assays. The efficacy of these functionalized materials were demonstrated in PBS, where we obsd. a >70% redn. in doxorubicin concn. over a period of 10 min, highlighting the viability of this as a method of drug capture.