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WIREs Nanomed Nanobiotechnol
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Advances in the development of aptamer drug conjugates for targeted drug delivery

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A key goal of modern medicine is target‐specific therapeutic intervention. However, most drugs lack selectivity, resulting in ‘off‐target’ side effects. To address the requirements of ‘targeted therapy,’ aptamers, which are artificial oligonucleotides, have been used as novel targeting ligands to construct aptamer drug conjugates (ApDC) that can specifically bind to a broad spectrum of targets, including diseased cells. Accordingly, the application of aptamers in targeted drug delivery has attracted broad interest due to their impressive selectivity and affinity, low immunogenicity, easy synthesis with high reproducibility, facile modification, and relatively rapid tissue penetration with no toxicity. Functionally, aptamers themselves can be used as macromolecular drugs, and they are also commonly used in biomarker discovery and targeted drug delivery. In this review, we will highlight the most recent advances in the development of aptamers and aptamer conjugates, and discuss their potential in targeted therapy. WIREs Nanomed Nanobiotechnol 2017, 9:e1438. doi: 10.1002/wnan.1438 This article is categorized under: Diagnostic Tools > Biosensing Diagnostic Tools > In Vitro Nanoparticle-Based Sensing Biology-Inspired Nanomaterials > Nucleic Acid-Based Structures
Schematic illustration of the cell‐SELEX process. (Reprinted with permission from Ref . Copyright 2015 Springer)
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Schematic illustration of stimuli‐responsive DNA nanohydrogel formation. (Reprinted with permission from Ref . Copyright 2015 American Chemical Society)
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Schematic diagrams of nanoplatforms based on aptamer‐conjugated gold nanoparticles for targeted drug delivery. (a) Apt‐HAuNS‐Dox nanoscale drug carrier. (b) AuNR‐based mesoporous silica nanocarrier. (Reprinted with permission from Ref . Copyright 2015 The Royal Society of Chemistry)
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Aptamer‐tethered DNA nanotrains (aptNTrs) used to transport drugs for theranostic applications. (a) Schematic diagram depicting the self‐assembly of aptNTrs from two partially complementary short hairpin monomers upon initiation by an aptamer‐tethered probe through hybridization chain reaction. Atomic‐Force Microscopy (AFM) images (1–3) show the morphologies of the corresponding nanostructures. (b) Drugs were specifically transported to target cancer cells by aptNTrs and unloaded to induce cytotoxicity to target cells. (c) Potent antitumor efficacy and reduced side effects of drugs transported by aptNTrs. Tumor volumes of subcutaneous CEM xenograft mouse tumors were measured after drug administration up to day 10 (n = 5). Asterisk on day 10 represents significant differences between tumor volumes of free Dox‐ and sgc8‐NTr‐Dox‐treated mice (*P < 0.05, n = 5; Student's t test). (d) Percentage of surviving mice after treatment initiation. (Reprinted with permission from Ref . Copyright 2013 PNAS)
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Sgc8c‐Dox conjugates for targeted drug delivery. (a) Schematic diagrams depicting sgc8c‐Dox covalent conjugation via acid‐labile linkages. (b) Distribution of sgc8c‐Dox conjugates inside CCRF‐CEM cells after incubation with cells for (1) 30 min, (2) 1 h, and (3) 2 h. From left to right, the fluorescence confocal images were monitored for sgc8c‐Dox, transferrin‐Alexa633, overlay of these two channels, and bright field channel, respectively. (c) Flow cytometry assay for the binding of biotin‐labeled TDO5 and sgc8c with three different cell lines: CCRF‐CEM, NB‐4, and Ramos. Cells (105/mL) were incubated with biotin‐labeled TDO5 and sgc8c at 37oC for 20 min in 100 μL culture medium without fetal bovine serum (FBS). After washing twice, cells were mixed with streptavidin‐(R‐phycoerythrin) (20 min on ice), and the fluorescence was determined by flow cytometry. (Reprinted with permission from Ref . Copyright 2009 John Wiley and Sons)
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Diagnostic Tools > In Vitro Nanoparticle-Based Sensing
Diagnostic Tools > Biosensing
Biology-Inspired Nanomaterials > Nucleic Acid-Based Structures

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