Genomic DNA coated 3D printed devices for chemotherapy

Abstract

Since the discovery of chemotherapy, 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. 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. Working together with medical doctors, computational fluid dynamics experts, and material chemists, we demonstrate the fabrication of DNA coated 3D printed 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 coating cheaply available genomic DNA to these materials, a departure from commonly used synthetic DNA. The efficacy of these coated materials were demonstrated in PBS, where we obsd. a marked decrease in doxorubicin concn. over a period of 20 min, highlighting the viability of this as a method of drug capture. We also discuss the in-vitro stability of these DNA coatings, with approx. 400 pg of DNA lost/mm² of coated material over 30 min in PBS at 37 C.

Additional details