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

Yee, Daryl W. and Hetts, Steven W. and Greer, Julia R. (2021) 3D-Printed Drug Capture Materials Based on Genomic DNA Coatings. ACS Applied Materials and Interfaces, 13 (35). pp. 41424-41434. ISSN 1944-8244. doi:10.1021/acsami.1c05209.

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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.

Item Type:Article
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URLURL TypeDescription
Yee, Daryl W.0000-0002-4114-6167
Greer, Julia R.0000-0002-9675-1508
Additional Information:© 2021 American Chemical Society. Received: March 20, 2021; Accepted: June 2, 2021; Published: June 14, 2021. This is a multidisciplinary effort sponsored by the National Cancer Institute (R01CA194533; principal investigator, Steven W. Hetts) involving investigators at multiple institutions. As such, all participants are part of the ChemoFilter Consortium and should be cited as collaborators. The Consortium’s members include the following individuals and institutions: Steven W. Hetts (University of California, San Francisco [hereafter, UCSF]), Mark W. Wilson (UCSF), Anand Patel (UCSF), Shuvo Roy (UCSF), Henry VanBrocklin (UCSF), Terilyn Moore (UCSF), Carol Stillson (UCSF), Aaron Losey (UCSF), Caroline Jordan (UCSF), Colin Yee (UCSF), Bridget Kilbride (UCSF), Jon Chan (UCSF), Nitash Balsara (University of California, Berkeley), Hee Jeung Oh (University of California, Berkeley), Julia R. Greer (Caltech), Daryl Yee (Caltech), Sankarganesh Krishnamoorthy (Caltech), Carl Blumenfeld (Caltech), Michael Schulz (Virginia Tech), Vitaliy Rayz (Purdue), and Nazanin Maani (Purdue). The authors would also like to acknowledge the following people at Caltech: Chi Ma for assistance with EDS analysis, Anthony Kwong and Prakriti Somani for assistance with carbon coatings, and Sammy Shaker for assistance with the experiments. In particular, the authors would also like to acknowledge Sankarganesh Krishnamoorthy and Jeong Hoon Ko for thoughtful discussions on the work. Author Contributions: The manuscript was written through contributions of all authors. All authors have given approval to the final version of the manuscript. D.W.Y., S.W.H., and J.R.G. conceived and designed the experiments. D.W.Y developed the coating methodology and conducted the experimental work. This work was supported by a grant from the National Cancer Institute (R01CA194533). The content is the sole responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The authors declare the following competing financial interest(s): A patent has been filed on this work.
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Subject Keywords:Coating materials, Genetics, Lattices, Antineoplastic agents, Genomics
Issue or Number:35
Record Number:CaltechAUTHORS:20210623-141714887
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Official Citation:3D-Printed Drug Capture Materials Based on Genomic DNA Coatings. Daryl W. Yee, Steven W. Hetts, and Julia R. Greer. ACS Applied Materials & Interfaces 2021 13 (35), 41424-41434; DOI: 10.1021/acsami.1c05209
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:109544
Deposited By: Tony Diaz
Deposited On:23 Jun 2021 18:37
Last Modified:13 Sep 2021 20:20

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