Light-Triggered Release of Bioactive Molecules from DNA Nanostructures.

Recent innovations in DNA nanofabrication allow the creation of intricately shaped nanostructures ideally suited for many biological applications. To advance the use of DNA nanotechnology for the controlled release of bioactive molecules, we report a general strategy that uses light to liberate encapsulated cargoes from DNA nanostructures with high spatiotemporal precision. Through the incorporation of a custom, photolabile cross-linker, we encapsulated cargoes ranging in size from small molecules to full-sized proteins within DNA nanocages and then released such cargoes upon brief exposure to light. This novel molecular uncaging technique offers a general approach for precisely releasing a large variety of bioactive molecules, allowing investigation into their mechanism of action, or finely tuned delivery with high temporal precision for broad biomedical and materials applications.

[1]  Wael Mamdouh,et al.  Single-molecule chemical reactions on DNA origami. , 2010, Nature nanotechnology.

[2]  Hao Yan,et al.  DNA Gridiron Nanostructures Based on Four-Arm Junctions , 2013, Science.

[3]  Björn Högberg,et al.  Spatial control of membrane receptor function using ligand nanocalipers , 2014, Nature Methods.

[4]  Pekka Orponen,et al.  DNA rendering of polyhedral meshes at the nanoscale , 2015, Nature.

[5]  Hao Yan,et al.  DNA-directed artificial light-harvesting antenna. , 2011, Journal of the American Chemical Society.

[6]  N. Seeman.  Nanomaterials based on DNA. , 2010, Annual review of biochemistry.

[7]  Shawn M. Douglas,et al.  A Logic-Gated Nanorobot for Targeted Transport of Molecular Payloads , 2012, Science.

[8]  Hao Yan,et al.  Structural DNA Nanotechnology: State of the Art and Future Perspective , 2014, Journal of the American Chemical Society.

[9]  Xue Han,et al.  Light sensitization of DNA nanostructures via incorporation of photo-cleavable spacers. , 2015, Chemical communications.

[10]  Jordi Soriano,et al.  Development of input connections in neural cultures , 2008, Proceedings of the National Academy of Sciences.

[11]  Shawn M. Douglas,et al.  DNA-nanotube-induced alignment of membrane proteins for NMR structure determination , 2007, Proceedings of the National Academy of Sciences.

[12]  Peng Yin,et al.  Casting inorganic structures with DNA molds , 2014, Science.

[13]  N. Seeman,et al.  Programmable materials and the nature of the DNA bond , 2015, Science.

[14]  M. Bathe,et al.  Quantitative prediction of 3D solution shape and flexibility of nucleic acid nanostructures , 2011, Nucleic acids research.

[15]  Tao Zhang,et al.  Hierarchical assembly of metal nanoparticles, quantum dots and organic dyes using DNA origami scaffolds. , 2013, Nature nanotechnology.

[16]  Johannes B. Woehrstein,et al.  Multiplexed 3D Cellular Super-Resolution Imaging with DNA-PAINT and Exchange-PAINT , 2014, Nature Methods.

[17]  Adam H. Marblestone,et al.  Rapid prototyping of 3D DNA-origami shapes with caDNAno , 2009, Nucleic acids research.

[18]  Hao Yan,et al.  Self-assembled DNA nanostructures for distance-dependent multivalent ligand-protein binding. , 2008, Nature nanotechnology.

[19]  N. Seeman.  DNA in a material world , 2003, Nature.

[20]  Shawn M. Douglas,et al.  Self-assembly of DNA into nanoscale three-dimensional shapes , 2009, Nature.

[21]  C. Holmes.  Model Studies for New o-Nitrobenzyl Photolabile Linkers: Substituent Effects on the Rates of Photochemical Cleavage. , 1997, The Journal of organic chemistry.

[22]  Hao Yan,et al.  Encapsulation of gold nanoparticles in a DNA origami cage. , 2011, Angewandte Chemie.

[23]  T. G. Martin,et al.  Facile and Scalable Preparation of Pure and Dense DNA Origami Solutions** , 2014, Angewandte Chemie.

[24]  P. Rothemund.  Folding DNA to create nanoscale shapes and patterns , 2006, Nature.

[25]  Björn Högberg,et al.  DNA origami delivery system for cancer therapy with tunable release properties. , 2012, ACS nano.

[26]  A. Kasko,et al.  Photodegradable macromers and hydrogels for live cell encapsulation and release. , 2012, Journal of the American Chemical Society.

[27]  H. Dietz,et al.  Dynamic DNA devices and assemblies formed by shape-complementary, non–base pairing 3D components , 2015, Science.

[28]  Rafael Yuste,et al.  RuBi-Glutamate: Two-Photon and Visible-Light Photoactivation of Neurons and Dendritic spines , 2009, Front. Neural Circuits.

[29]  Hao Yan,et al.  DNA origami as a carrier for circumvention of drug resistance. , 2012, Journal of the American Chemical Society.

[30]  Mingdi Yan,et al.  Stereoselective synthesis of light-activatable perfluorophenylazide-conjugated carbohydrates for glycoarray fabrication and evaluation of structural effects on protein binding by SPR imaging. , 2011, Organic & biomolecular chemistry.

[31]  Hao Yan,et al.  Lattice-free prediction of three-dimensional structure of programmed DNA assemblies , 2014, Nature Communications.

[32]  M. Finn,et al.  Analysis and optimization of copper-catalyzed azide-alkyne cycloaddition for bioconjugation. , 2009, Angewandte Chemie.

[33]  G. Ellis‐Davies,et al.  Optically selective two-photon uncaging of glutamate at 900 nm. , 2013, Journal of the American Chemical Society.

[34]  Yasushi Miyashita,et al.  Dendritic spine geometry is critical for AMPA receptor expression in hippocampal CA1 pyramidal neurons , 2001, Nature Neuroscience.