Visualization of the Cellular Uptake and Trafficking of DNA Origami Nanostructures in Cancer Cells

• Type of Material: Article
• Authors: Pengfei Wang, Georgia Institute of Technology; Aminur Rahman, Emory University; Zhixiang Zhao, Emory University; Kristin Weiss, Georgia Institute of Technology; Chao Zhang, Emory University; Zhengjia Chen, Emory University; Selwyn Hurwitz, Emory University; Georgia Chen, Emory University; Dong Shin, Emory University; Yonggang Ke, Emory University
• Language: English
• Date: 2018-02-21
• Publisher: American Chemical Society
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2018 American Chemical Society
• Final Published Version (URL): http://dx.doi.org/10.1021/jacs.7b09024
• Title of Journal or Parent Work: Journal of the American Chemical Society
• Volume: 140
• Issue: 7
• Start Page: 2478
• End Page: 2484
• Grant/Funding Information: This work was supported by grants from the NCI R21EB022828-01A1 to D.M.S. and Y.K., and Winship Cancer Institute grant #IRG-14-188-0 from the American Cancer Society to Y.K.; The EM data was collected on a Hitachi HT7700 120 kv TEM supported by the Georgia Clinical and Translational Science Alliance under award number UL1TR002378 to the Robert P. Apkarian Integrated Electron Microsocpy Core at the Emory College of Arts and Sciences and the Emory University School of Medicine.; This research used an AFM supported by NIH grants GM084070 and 3R01GM084070-07S1 to Laura Finzi in the Department of Physics at Emory University. We thank Dr. Anthea Hammond for her assistance in critical reading and editing of the manuscript.
• Keywords: Gold nanoparticles; Chemistry, Multidisciplinary; Drug resistance; Mechanisms; Folding DNA; Plasmonic nanostructures; Nanoscale shapes; Science & Technology; Chemistry; Scavenger receptors; Delivery; Therapy; Physical Sciences; Endocytosis
• Research Categories: Biology, Genetics; Health Sciences, Oncology; Chemistry, Biochemistry

Abstract

DNA origami is a promising molecular delivery system for a variety of therapeutic applications including cancer therapy, given its capability to fabricate homogeneous nanostructures whose physicochemical properties (size, shape, surface chemistry) can be precisely tailored. However, the correlation between DNA-origami design and internalization efficiency in different cancer cell lines remains elusive. We investigated the cellular uptake of four DNA-origami nanostructures (DONs) with programmed sizes and shapes in multiple human cancer cell lines. The cellular uptake efficiency of DONs was influenced by size, shape, and cell line. Scavenger receptors were responsible for the internalization of DONs into cancer cells. We observed distinct stages of the internalization process of a gold nanoparticle (AuNP)-tagged rod-shape DON, using high-resolution transmission electron microscopy. This study provides detailed understanding of cellular uptake and intracellular trafficking of DONs in cancer cells, and offers new insights for future optimization of DON-based drug delivery systems for cancer treatment.