Site-Specific Surface Functionalization of Gold Nanorods Using DNA Origami Clamps Chenqi Shen, † Xiang Lan, † Xuxing Lu, † Travis A. Meyer, ‡ Weihai Ni, † Yonggang Ke,* ,‡ and Qiangbin Wang* ,† † Key Laboratory of Nano-Bio Interface, Division of Nanobiomedicine and i-Lab, Suzhou Institute of Nano-Tech and Nano-Bionics, Chinese Academy of Sciences, Suzhou 215123, China ‡ Wallace H. Coulter Department of Biomedical Engineering, Georgia Tech and Emory University, Emory School of Medicine, Atlanta, Georgia 30322, United States * S Supporting Information ABSTRACT: Precise control over surface functionalities of nanomaterials offers great opportunities for fabricating complex functional nanoarchitectures but still remains challenging. In this work, we successfully developed a novel strategy to modify a gold nanorod (AuNR) with specific surface recognition sites using a DNA origami clamp. AuNRs were encapsulated by the DNA origami through hybridization of single-stranded DNA on the AuNRs and complementary capture strands inside the clamp. Another set of capture strands on the outside of the clamp create the specific recognition sites on the AuNR surface. By means of this strategy, AuNRs were site- specifically modified with gold nanoparticles at the top, middle, and bottom of the surface, respectively, to construct a series of well-defined heterostructures with controlled “chemical valence”. Our study greatly expands the utility of DNA origami as a tool for building complex nanoarchitectures and represents a new approach for precise tailoring of nanomaterial surfaces. S urface functionalities of nanomaterials play a particularly decisive role in regulating their physical and chemical properties, such as biocompatibility 1 and catalytic activity, 2 because of their high surface-to-volume ratios. Therefore, methods for surface modification of nanoparticles have been investigated in depth. Classic surface modification processes isotropically decorate the whole nanoparticle surface, thus creating a single type of surface functionality. 3 In recent years, more efforts have been dedicated to fabricating surface- anisotropic nanoparticles displaying multiple surface function- alities 4 by utilizing methods such as deposition, 5 lithography, 6 templating, 7 etc. Nonetheless, these anisotropic functionaliza- tion methods still lack the precision needed to manufacture functional nanomaterials with custom-designed individual recognition sites. A new strategy that can generate nanomaterial surfaces with arbitrary single-site modifications could facilitate the construction of new nanomaterials with greater complexity and potentially new functionalities. DNA has emerged as a powerful molecule for surface- anisotropic functionalization 8 because of its outstanding features including sequence programmability, 9 distinctive molecular recognition, 10 and facile chemical modifications. 11 For instance, Mirkin and co-workers 12 fabricated gold nano- particles (AuNPs) asymmetrically surface-functionalized with both normal and extended oligonucleotides with the assistance of magnetic microparticles, and these anisotropic particles were further used as building blocks for the construction of unique heterostructures. With the advancement of DNA nano- technology, self-assembled DNA origami has proven to be a versatile platform for constructing fully addressable, arbitrary- shaped nanostructures. 13 Noble-metal nanoparticles, 14 quan- tum dots, 15 fluorescent probes, 16 and biomolecules 17 have been precisely docked to specific locations on DNA origami scaffolds to fabricate a variety of well-ordered nanoarchitectures. Therefore, the use of DNA origami could be a promising technique to realize single-site surface modification of nano- particles, which has not been reported before. In this work, we developed a novel strategy to render a gold nanorod (AuNR) with specific surface recognition sites using a DNA origami nanostructure. An open DNA origami nano- structure, termed a “DNA clamp”, was designed with capture strands on the inside faces, causing the DNA clamp to close around the AuNR after hybridization with the complementary DNA strands on the AuNR surface, fully encapsulating the nanorod surface. The DNA-clamp-covered AuNR possesses a fully addressable surface, offering unprecedented site-specific functionality and promising more precise construction of complex nanostructures. Furthermore, this new approach expands the usage of DNA origami from addressable assembly of functional components to site-specific surface modification of nanomaterials, enabling the rational design and precise fabrication of functional nanomaterials and nanostructures. Figure 1 schematically illustrates the step-by-step process for surface functionalization of the AuNR. First, a DNA clamp consisting of two half-tubes with equal lengths of 56 nm linked by two flexible hinges was designed. A total of 16 capture strands were arranged in three stripes protruding from the inside faces of the DNA clamp. A 13 nm × 38 nm AuNR functionalized with thiolated single-stranded DNA (ssDNA) was mixed with the self-assembled DNA clamp, leading to hybridization of ssDNA on the AuNR surface with the complementary capture strands inside the clamp. This Received: November 4, 2015 Published: January 29, 2016 Communication pubs.acs.org/JACS © 2016 American Chemical Society 1764 DOI: 10.1021/jacs.5b11566 J. Am. Chem. Soc. 2016, 138, 1764-1767