Time-Lapse Live Cell Imaging to Monitor Doxorubicin Release from DNA Origami Nanostructures


Self-assembled DNA nanostructures have attracted significant research interest in biomedical applications because of their excellent programmability and biocompatibility. To develop multifunctional drug delivery from DNA nanostructures, considerable key information is still needed for clinical application. Traditional fixed endpoint assays do not reflect the dynamic and heterogeneous responses of cells with regard to drugs, and may lead to the misinterpretation of experimental results. For the first time, an integrated time-lapse live cell imaging system was used to study the cellular internalization and controlled drug release profile of three different shaped DNA origami/doxorubicin (DOX) complexes for three days. Our results demonstrated the dependence of DNA nanostructures on shape for drug delivery efficiency, while the rigid 3D DNA origami triangle frame exhibited enhanced cellular uptake capability, as compared with flexible 2D DNA structures. In addition, the translocation of released DOX into the nucleus was proved by fluorescence microscopy, in which a DOX-loaded 3D DNA triangle frame displayed a stronger accumulation of DOX in nuclei. Moreover, given the facile drug loading and auto fluorescence of the anti-cancer drug, DOX, our results suggest that the DNA nanostructure is a promising candidate, as a label-free nanocarrier, for DOX delivery, with great potential for anticancer therapy as well.




This article is part of the themed collection: 2018 Journal of Materials Chemistry B HOT Papers (recommended by referees).

This work was supported by University of Missouri Research Board, Material Research Center and Center of Biomedical Research of Missouri S&T to R. W. This study was supported, in part, by National Institutes of Health grants R01 CA178831 and CA191785, Department of Defense Breast Cancer Research Program Breakthrough Level II grant BC151845 to L. X.

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© 2018 Royal Society of Chemistry, All rights reserved.

Publication Date

21 Mar 2018