DNA Nanoclews for Stimuli-Responsive Anticancer Drug Delivery
The technique of rolling circle amplification (RCA) emerged recently as a robust tool to generate the regularly patterned DNA structures in addition to its long-recognized ability of amplifying biological signals. Here, we demonstrate the strategy of RCA-
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DNA Nanoclews for Stimuli-Responsive Anticancer Drug Delivery Wujin Sun and Zhen Gu
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Introduction
In addition to DNA’s role as a genetic material to transmit hereditary information, the development of DNA nanotechnology approached DNA as a highly programmable and biocompatible generic material based on Watson-Crick base pairing, revealing huge potential in drug delivery applications (Sun and Gu 2015). As a facile technique to synthesize periodic single-stranded DNA (ssDNA) or RNA, rolling circle replication technique has evolved into a platform technology for preparing nucleic acid structures spanning the spatial range from nano-, micro- to meta-scales (Sun et al. 2015b). With its high programmability and predictability, exquisite DNA nanostructures, such as DNA nano-tetrahedron with multiple targeting ligands (Lee et al. 2012a) or DNA nano-box with a controllable lid (Andersen et al. 2009), could be obtained by W. Sun (*) Joint Department of Biomedical Engineering, University of North Carolina at Chapel Hill and North Carolina State University, Raleigh, NC 27695, USA Division of Molecular Pharmaceutics and Center for Nanotechnology in Drug Delivery, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA e-mail: [email protected] Z. Gu, Ph.D. (*) Joint Department of Biomedical Engineering, University of North Carolina at Chapel Hill and North Carolina State University, Raleigh, NC 27695, USA Division of Molecular Pharmaceutics and Center for Nanotechnology in Drug Delivery, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA Department of Medicine, University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA e-mail: [email protected] © Springer International Publishing Switzerland 2016 V.V. Demidov (ed.), Rolling Circle Amplification (RCA), DOI 10.1007/978-3-319-42226-8_12
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meticulously tuning the complementary sequences of DNA strands with the assistance of computer-based software (Douglas et al. 2009). Additionally, DNA is a polyvalent polymer that could be easily modified or functionalized to generate structurally and functionally more complicated nanoparticles by means of small molecule intercalation (Mo et al. 2014a), nucleic acid hybridization (Jang et al. 2015), electrostatic adsorption (Guo and Huang 2012), or covalent conjugation (Udomprasert et al. 2014). Various types of therapeutically valuable molecules could be tethered or loaded into DNA nanoparticles, including ligands like antibody (Douglas et al. 2012) or aptamer (Wu et al. 2010) for targeted drug delivery; small molecules like doxorubicin (DOX, aka adriamycin) (Zhao et al. 2012) or reactive oxygen species generating photosensitizers for anticancer therapy (Wang et al. 2011); functional nucleic acids like siRNA (Lee et al. 2012b) and antisense nucleotides (Roh et al. 2014) for mRNA regulation; DNA binding proteins like transcription factors for epigenetic regulation (Lee et al. 2015); or the CRISPR-Cas9 system
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