Nuclease-Resistant DNA via High-Density Packing in Polymeric Micellar Nanoparticle Coronas
ABSTRACT Herein, we describe a polymeric micellar nanoparticle capable of rendering nucleic acids resistant to nuclease digestion. This approach relies on utilizing DNA as the polar headgroup of a DNA-polymer amphiphile in order to assemble well-defined, discrete nanoparticles. Dense packing of DNA in the micelle corona allows for hybridization of complementary oligonucleotides while prohibiting enzymatic degradation. We demonstrate the preparation, purification, and characterization of the nanoparticles, then describe their resistance to treatment with endo- and exonucleases including snake-venom phosphodiesterase (SVP), a common, general DNA digestion enzyme.
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ABSTRACT: A new tricarbocyanine-based chemosensor exhibited a dramatic Al3+-specific fluorescence turn-on response in the Near-Infrared (NIR) region. The receptor was found to be highly selective towards Al3+ over other metal ions in physiological condition. The sensor was also capable to sense Al3+ in complex medium like environment samples (tap water, lake water and river water). The sensor was non-toxic and could thus be employed as an imaging probe for detecting intracellular Al3+ in live cells. Interestingly, upon interaction with DNA in solution, the L-Al3+ ensemble rendered tracking of DNase activity in solution through a systematic reduction in the fluorescence emission intensity.Analytica Chimica Acta 04/2015; DOI:10.1016/j.aca.2015.04.032 · 4.52 Impact Factor
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ABSTRACT: Herein, we report the synthesis of DNA-functionalized infinite-coordination-polymer (ICP) nanoparticles as biocompatible gene-regulation agents. ICP nanoparticles were synthesized from ferric nitrate and a ditopic 3-hydroxy-4-pyridinone (HOPO) ligand bearing a pendant azide. Addition of Fe(III) to a solution of the ligand produced nanoparticles, which were colloidally unstable in the presence of salts. Conjugation of DNA to the Fe(III) -HOPO ICP particles by copper-free click chemistry afforded colloidally stable nucleic-acid nanoconstructs. The DNA-ICP particles, when cross-linked through sequence-specific hybridization, exhibited narrow, highly cooperative melting transitions consistent with dense DNA surface loading. The ability of the DNA-ICP particles to enter cells and alter protein expression was also evaluated. Our results indicate that these novel particles carry nucleic acids into mammalian cells without the need for transfection agents and are capable of efficient gene knockdown.Angewandte Chemie International Edition in English 11/2014; 54(2). DOI:10.1002/anie.201407946 · 13.45 Impact Factor
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ABSTRACT: We describe a novel two-step method, starting from bulk silicon wafers, to construct DNA conjugated silicon nanoparticles (SiNPs). This method first utilizes reactive high-energy ball milling (RHEBM) to obtain alkene grafted SiNPs. The alkene moieties are subsequently reacted with commercially available thiol-functionalized DNA via thiol-ene click chemistry to produce SiNP DNA conjugates wherein the DNA is attached through a covalent thioether bond. Further, to show the utility of this synthetic strategy, we illustrate how these SiNP ODN conjugates can detect cancer-associated miR-21 via a fluorescence ON strategy. Given that an array of biological molecules can be prepared with thiol termini and that SiNPs are biocompatible and biodegradable, we envision that this synthetic protocol will find utility in salient SiNP systems for potential therapeutic and diagnostic applications.Bioconjugate Chemistry 09/2014; 25(10). DOI:10.1021/bc5004026 · 4.82 Impact Factor