A Comprehensive Screen of Metal Oxide Nanoparticles for DNA Adsorption, Fluorescence Quenching, and Anion Discrimination

This document is the Accepted Manuscript version of a Published Work that appeared in final form in Applied Materials & Interfaces, copyright © American Chemical Society after peer review and technical editing by publisher. To access the final edited and published work see http://dx.doi.org/10.1021/acsami.5b08004Although DNA has been quite successful in metal cation detection, anion detectioin remains challenging because of the charge repulsion. Metal oxides represent a very important class of materials, and different oxides might interact with anions differently. In this work, a comprehensive screen of common metal oxide nanoparticles (MONPs) was carried out for their ability to adsorb DNA, quench fluorescence, and release adsorbed DNA in the presence of target anions. A total of 19 MONPs were studied, including Al2O3, CeO2, CoO, Co3O4, Cr2O3, Fe2O3, Fe3O4, In2O3, ITO, Mn2O3, NiO, SiO2, SnO2, a-TiO2 (anatase), r-TiO2 (rutile), WO3, Y2O3, ZnO, ZrO2. These MONPs have different DNA adsorption affinity. Some adsorb DNA without quenching the fluorescence, while others strongly quench adsorbed fluorophores. They also display different affinity toward anions probed by DNA desorption. Finally, CeO2, Fe3O4, and ZnO were used to form a sensor array to discriminate phosphate, arsenate, and arsenite from the rest using linear discriminant analysis. This study not only provides a solution for anion discrimination using DNA as a signaling molecule but also provides insights into the interface of metal oxides and DNA.Natural Sciences and Engineering Research Council || Discovery and Strategic Project Grant: STPGP-447472-2013 05576

Accelerating peroxidase mimicking nanozymes using DNA

DNA-capped iron oxide nanoparticles are nearly 10-fold more active as a peroxidase mimic for TMB oxidation than naked nanoparticles. To understand the mechanism, the effect of DNA length and sequence is systematically studied, and other types of polymers are also compared. This rate enhancement is more obvious with longer DNA and, in particular, poly-cytosine. Among the various polymer coatings tested, DNA offers the highest rate enhancement. A similar acceleration is also observed for nanoceria. On the other hand, when the positively charged TMB substrate is replaced by the negatively charged ABTS, DNA inhibits oxidation. Therefore, the negatively charged phosphate backbone and bases of DNA can increase TMB binding by the iron oxide nanoparticles, thus facilitating the oxidation reaction in the presence of hydrogen peroxide.University of Waterloo || Canadian Foundation for Innovation || Natural Sciences and Engineering Research Council || Ontario Ministry of Research and Innovation |

DNA adsorption by magnetic iron oxide nanoparticles and its application for arsenate detection

Iron oxide nanoparticles adsorb fluorescently labeled DNA oligonucleotides via the backbone phosphate and quench fluorescence. Arsenate displaces adsorbed DNA to increase fluorescence, allowing detection of arsenate down to 300 nM. This is a new way of using DNA: analyte recognition relies on its phosphate instead of the bases

DNA Adsorption by Indium Tin Oxide (ITO) Nanoparticles

This document is the Accepted Manuscript version of a Published Work that appeared in final form in Langmuir, copyright © American Chemical Society after peer review and technical editing by publisher. To access the final edited and published work see http://dx.doi.org/10.1021/la503917jThe high conductivity and optical transparency of indium tin oxide (ITO) has made it a popular material in the electronic industry. Recently, its application in biosensors is also explored. To understand its biointerface chemistry, we herein investigate its interaction with fluorescently labeled single-stranded oligonucleotides using ITO nanoparticles (NPs). The fluorescence of DNA is efficiently quenched after adsorption, and the interaction between DNA and ITO NPs is strongly dependent on the surface charge of ITO. At low pH, the ITO surface is positively charged to afford a high DNA adsorption capacity. Adsorption is also influenced by the sequence and length of DNA. For its components, In2O3 adsorbs DNA more strongly while SnO2 repels DNA at neutral pH. The DNA adsorption property of ITO is an averaging result from both components. DNA adsorption is confirmed to be mainly by the phosphate backbone via displacement experiments using free phosphate or DNA bases. Last, DNA-induced DNA desorption by forming duplex DNA is demonstrated on ITO, while the same reaction is more difficult to achieve on other metal oxides including CeO2, TiO2, and Fe3O4 because these particles adsorb DNA more tightly.University of Waterloo || Canadian Foundation for Innovation || Natural Sciences and Engineering Research Council || Ontario Ministry of Research and Innovation |

Mechanisms of DNA Sensing on Graphene Oxide

This document is the Accepted Manuscript version of a Published Work that appeared in final form in Analytical Chemistry copyright © American Chemical Society after peer review and technical editing by publisher. To access the final edited and published work see Liu, B., Sun, Z., Zhang, X., & Liu, J. (2013). Mechanisms of DNA Sensing on Graphene Oxide. Analytical Chemistry, 85(16), 7987–7993. https://doi.org/10.1021/ac401845pAdsorption of a fluorophore-labeled DNA probe by graphene oxide (GO) produces a sensor that gives fluorescence enhancement in the presence of its complementary DNA (cDNA). While many important analytical applications have been demonstrated, it remains unclear how DNA hybridization takes place in the presence of GO, hindering further rational improvement of sensor design. For the first time, we report a set of experimental evidence to reveal a new mechanism involving nonspecific probe displacement followed by hybridization in the solution phase. In addition, we show quantitatively that only a small portion of the added cDNA molecules undergo hybridization while most are adsorbed by GO to play the displacement role. Therefore, it is possible to improve signaling by raising the hybridization efficiency. A key innovation herein is using probes and cDNA with a significant difference in their adsorption energy by GO. This study offers important mechanistic insights into the GO/DNA system. At the same time, it provides simple experimental methods to study the biomolecular reaction dynamics and mechanism on a surface, which may be applied for many other biosensor systems.University of Waterloo || Canadian Foundation for Innovation || Natural Sciences and Engineering Research Council || Ontario Ministry of Research and Innovation |

Cation-Size-Dependent DNA Adsorption Kinetics and Packing Density on Gold Nanoparticles: An Opposite Trend

This document is the Accepted Manuscript version of a Published Work that appeared in final form in Langmuir, copyright © American Chemical Society after peer review and technical editing by publisher. To access the final edited and published work see Liu, B., Kelly, E. Y., & Liu, J. (2014). Cation-Size-Dependent DNA Adsorption Kinetics and Packing Density on Gold Nanoparticles: An Opposite Trend. Langmuir, 30(44), 13228–13234. https://doi.org/10.1021/la503188hThe property of DNA is strongly influenced by counterions. Packing a dense layer of DNA onto a gold nanoparticle (AuNP) generates an interesting colloidal system with many novel physical properties such as a sharp melting transition, protection of DNA against nucleases, and enhanced complementary DNA binding affinity. In this work, the effect of monovalent cation size is studied. First, for free AuNPs without DNA, larger group 1A cations are more efficient in inducing their aggregation. The same trend is observed with group 2A metals using AuNPs capped by various self-assembled monolayers. After establishing the salt range to maintain AuNP stability, the DNA adsorption kinetics is also found to be faster with the larger Cs+ compared to the smaller Li+. This is attributed to the easier dehydration of Cs+, and dehydrated Cs+ might condense on the AuNP surface to reduce the electrostatic repulsion effectively. However, after a long incubation time with a high salt concentration, Li+ allows ∼30% more DNA packing compared to Cs+. Therefore, Li+ is more effective in reducing the charge repulsion among DNA, and Cs+ is more effective in screening the AuNP surface charge. This work suggests that physicochemical information at the bio/nanointerface can be obtained by using counterions as probes.University of Waterloo || Canadian Foundation for Innovation || Natural Sciences and Engineering Research Council || Ontario Ministry of Research and Innovation |

Fluorescent sensors using DNA-functionalized graphene oxide

The final publication is available at Springer via http://dx.doi.org/10.1007/s00216-014-7888-3In the past few years, graphene oxide (GO) has emerged as a unique platform for developing DNA-based biosensors, given the DNA adsorption and fluorescence-quenching properties of GO. Adsorbed DNA probes can be desorbed from the GO surface in the presence of target analytes, producing a fluorescence signal. In addition to this initial design, many other strategies have been reported, including the use of aptamers, molecular beacons, and DNAzymes as probes, label-free detection, utilization of the intrinsic fluorescence of GO, and the application of covalently linked DNA probes. The potential applications of DNA-functionalized GO range from environmental monitoring and cell imaging to biomedical diagnosis. In this review, we first summarize the fundamental surface interactions between DNA and GO and the related fluorescence-quenching mechanism. Following that, the various sensor design strategies are critically compared. Problems that must be overcome before this technology can reach its full potential are described, and a few future directions are also discussed.University of Waterloo || Natural Sciences and Engineering Research Council || Ontario Ministry of Research and Innovation || Foundation for Shenghua Scholar || National Natural Science Foundation of China || Grant No. 81301258, 21301195 Postdoctoral Science Foundation of Central South University and Hunan province ||Grant No. 124896 China Postdoctoral Science Foundation || Grant No. 2013M540644 Hunan Provincial Natural Science Foundation of China || Grant No. 13JJ4029 Specialized Research Fund for the Doctoral Program of Higher Education of China || Grant No. 2013016212007

Orthogonal Adsorption Onto Nano-Graphene Oxide Using Different Intermolecular Forces for Multiplexed Delivery

This is the peer reviewed version of the following article: Wang, F., Liu, B., Ip, A. C.-F., & Liu, J. (2013). Orthogonal Adsorption Onto Nano-Graphene Oxide Using Different Intermolecular Forces for Multiplexed Delivery. Advanced Materials, 25(30), 4087–4092, which has been published in final form at https://doi.org/10.1002/adma.201301183. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving.Nano-graphene oxide can adsorb both doxorubicin and zwitterionic dioleoyl-sn-glycero-3-phosphocholine (DOPC) liposomes in an orthogonal and non-competing manner with high capacities based on different surface and intermolecular forces taking place on the heterogeneous surface of the graphene oxide. The system forms stable colloids, allowing co-delivery of both cargos to cancer cells.University of Waterloo || Canadian Foundation for Innovation || Natural Sciences and Engineering Research Council || Ontario Ministry of Research and Innovation |

Characterization of glucose oxidation by gold nanoparticles using nanoceria

The final publication is available at Elsevier via http://dx.doi.org/10.1016/j.jcis.2014.04.025." © 2014. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/Gold nanoparticles (AuNPs) can oxidize glucose, producing hydrogen peroxide and gluconic acid, which are the same products as those generated by glucose oxidase (GOx). In this regard, AuNPs are a nanozyme. Herein, a new colorimetric method is developed to understand the surface chemistry of gold nanoparticles for this oxidation reaction. The color of nanoceria is changed to yellow by the hydrogen peroxide generated during glucose oxidation. Using this assay, we find that adsorption of small molecules such as citrate does not deactivate AuNPs, while adsorption of polymers including serum proteins and high molecular weight polyethylene glycol inhibits glucose oxidation. In addition to glucose, AuNPs can also oxidize galactose. Therefore, this reaction is unlikely to be directly useful for glucose detection for biomedical applications. On the other hand, AuNPs might serve as a general oxidase for a broad range of substrates. The glucose oxidation reaction is slower at lower pH. Since the reaction generates an acid product, glucose oxidation becomes slower as the reaction proceeds. The effects of temperature, AuNP size, and reaction kinetics have been systematically studied. This work provides new insights regarding the surface chemistry of AuNPs as a nanozyme.University of Waterloo || Canadian Foundation for Innovation || Natural Sciences and Engineering Research Council || Ontario Ministry of Research and Innovation |

Rationally Designed Nucleobase and Nucleotide Coordinated Nanoparticles for Selective DNA Adsorption and Detection

This document is the Accepted Manuscript version of a Published Work that appeared in final form in Analytical Chemistry copyright © American Chemical Society after peer review and technical editing by publisher. To access the final edited and published work see Wang, F., Liu, B., Huang, P.-J. J., & Liu, J. (2013). Rationally Designed Nucleobase and Nucleotide Coordinated Nanoparticles for Selective DNA Adsorption and Detection. Analytical Chemistry, 85(24), 12144–12151. https://doi.org/10.1021/ac4033627Nanomaterials for DNA adsorption are useful for sequence-specific DNA detection. Current materials for DNA adsorption employ electrostatic attraction, hydrophobic interaction, or π–π stacking, none of which can achieve sequence specificity. Specificity might be improved by involving hydrogen bonding and metal coordination. In this work, a diverse range of nucleobase/nucleotide (adenine, adenosine, adenosine 5′-triphosphate (ATP), adenosine 5′-monophosphate (AMP), and guanosine 5′-triphosphate (GTP)) coordinated materials containing various metal ions (Au(III), Ag(I), Ce(III), Gd(III), and Tb(III)) are prepared. In most cases, nanoparticles are formed. These materials have different surface charges, and positively charged particles only show nonspecific DNA adsorption. Negatively charged materials give different adsorption kinetics for different DNA sequences, where complementary DNA homopolymers are adsorbed faster than other sequences. Therefore, the bases in the coordinated materials can still form base pairs with the DNA. The adsorption strength is mainly controlled by the metal ions, where Au shows the strongest adsorption while lanthanides are weaker. These materials can be used as sensors for DNA detection and can also deliver DNA into cells with no detectable toxicity. By tuning the nanoparticle formulation, enhanced detection can be achieved. This study is an important step toward rational design of materials to achieve specific interactions between biomolecules and synthetic nanoparticle surfaces.University of Waterloo || Canadian Foundation for Innovation || Ontario Ministry of Research & Innovation || Natural Sciences and Engineering Research Council |