Drug capture materials based on genomic DNA-functionalized magnetic nanoparticles

Creators: Blumenfeld, Carl M.; Schulz, Michael D.; Aboian, Mariam S.; Wilson, Mark W.; Moore, Terilynn; Hetts, Steven W.; Grubbs, Robert H.

Abstract

Chemotherapy agents are notorious for producing severe side-effects. One approach to mitigating this off-target damage is to deliver the chemotherapy directly to a tumor via transarterial infusion, or similar procedures, and then sequestering any chemotherapeutic in the veins draining the target organ before it enters the systemic circulation. Materials capable of such drug capture are yet to be fully realized. Here, we report the covalent attachment of genomic DNA to iron-oxide nanoparticles. With these magnetic materials, we captured three common chemotherapy agents—doxorubicin, cisplatin, and epirubicin—from biological solutions. We achieved 98% capture of doxorubicin from human serum in 10 min. We further demonstrate that DNA-coated particles can rescue cultured cardiac myoblasts from lethal levels of doxorubicin. Finally, the in vivo efficacy of these materials was demonstrated in a porcine model. The efficacy of these materials demonstrates the viability of genomic DNA-coated materials as substrates for drug capture applications.

Additional Information

© The Author(s) 2018. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. Received: 12 May 2017 Accepted: 20 June 2018. Published online: 20 July 2018. The authors gratefully acknowledge the financial support from the NIH (R01CA194533, Hetts; 5T32EB001631-13, Aboian). Confocal imaging was performed in the Biological Imaging Facility, with the support of the Caltech Beckman Institute and the Arnold and Mabel Beckman Foundation. The authors additionally acknowledge support from the Beckman Institute of the California Institute of Technology to the Molecular Materials Research Center. The authors wish to thank Dr. Andres Collazo for assistance with imaging, Mr. Daryl Yee for assistance with X-ray photoelectron spectroscopy, and Wesley Kuo for performing flow model experiments and for assisting with fluoroscopy image acquisition during in vivo porcine experiments. We would like to thank UCSF Interventional Radiology laboratory members for assisting with in vivo porcine experiments including Carol Stillson, Dr. Maythem Saeed, Anqi Liang, Joshua Fisher, Jay Yu, and Dr. Caroline Jordan. We would also like to thank Sravani Kondapavulur for expert advice on the assembly of the magnetic device. These authors contributed equally: Carl M. Blumenfeld, Michael D. Schulz. Author Contributions: C.M.B. and M.D.S. designed materials and devices, synthesized materials, and assisted with in vitro experiments. M.S.A performed cell culture experiments, and performed in vitro and in vivo experiments with the magnetic device. T.M., M.W.W., and S.W.H. supervised and performed in vivo experiments. R.H.G. and S.W.H. supervised the project. All authors discussed the results. Data availability: All data supporting the findings of this study are available within the article and its Supplementary Information. All other data are available from the corresponding author upon reasonable request. Competing interests: S.W.H. and M.W.W. have a royalty agreement through the University of California and currently licensed to Penumbra, Inc., should a medical device resulting from the underlying endovascular filtration technology be developed and marketed. A patent application (WO2018048829A1) has been filed by the California Institute of Technology that covers the materials described in this paper. The remaining authors declare no competing interests.

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