3D-Printed Drug Capture Materials Based on Genomic DNA Coatings

基于基因组 DNA 涂层的 3D 打印药物捕获材料

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作者:Daryl W Yee, Steven W Hetts, Julia R Greer

Abstract

The toxic side effects of chemotherapy have long limited its efficacy, prompting expensive and long-drawn efforts to develop more targeted cancer therapeutics. An alternative approach to mitigate off-target toxicity is to develop a device that can sequester chemotherapeutic agents from the veins that drain the target organ before they enter systemic circulation. This effectively localizes the chemotherapy to the target organ, minimizing any hazardous side effects. 3D printing is ideal for fabricating these devices, as the geometric control afforded allows us to precisely dictate its hemodynamic performance in vivo. However, the existing materials compatible with 3D printing do not have drug-binding capabilities. Here, we report the stable coating of genomic DNA on a 3D-printed structure for the capture of doxorubicin. Genomic DNA is an effective chemotherapeutic-agent capture material due to the intrinsic DNA-targeting mechanism of action of these drugs. Stable DNA coatings were achieved through a combination of electrostatic interactions and ultraviolet C (UVC, 254 nm) cross-linking. These UVC cross-linked DNA coatings were extremely stable-leaching on average 100 pg of genomic DNA per mm2 of 3D-printed structure over a period of 30 min. In vitro studies of these materials in phosphate buffered saline and human serum demonstrated that they were able to capture, on average, 72 and 60 ng of doxorubicin per mm2 of structure, respectively. The stability and efficacy of these genomic DNA-coated 3D-printed materials represent a significant step forward towards the translation of these devices to clinical applications for the potential improvement of chemotherapy treatment.

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