Our group is interested in studying two and three dimensional nanoparticles for addressing biological, biomedical and environmental challenges.
Mainly our researh program can be categorized in three researh directions.
I. Three dimensional nanoparticle and oligonucleotide assemblies for ultrasensitive detection: The goal of this research direction is to create a transformative approach for the ultrasensitive, cost-efficient and programmable detection of three classes of analytes: (a) oligonucleotides (DNA/RNA), (b) proteins and (c) heavy metal ions using DNA nanotechnology coupled with metallic particles. Our studies illustrate that our instrument-free colorimetric detection approach is simple, but much more sensitive than any other colorimetric methods reported to date. The proposed methodology offers detection of the target analytes from their native environment without any isolation steps. This is particularly important for point-of-care diagnosis or real-time environmental monitoring for translational research. The detection is multiplexed where a single sensor template can be programmed for the detection of multiple analytes in various combinations and formats. The approach relies on the important discovery in the DNA nanotechnology field known as hybridization chain reaction (HCR), where a single short stranded DNA can trigger the formation of a large double stranded DNA polymer by activating two metastable short DNA hairpins. Our goal is to couple the enzyme-free amplification and programmable feature of HCR with the physical properties of nano and micro particles to develop state-of-the-art detection methodologies. This disruptive method will likely revolutionize the current approaches of constructing metallic particle and oligonucleotide based sensors.
Reprogrammable colorimetric detection Detection and classification Ebola Virus Biomarkers Heavy metal ion detection from environmental resources
Endogenous cancer biomarker detection
Publications on topic I:
1. Rapid Visual Screening and Programmable Subtype Classification of Ebola Virus Biomarkers, Advanced Healthcare Materials, 2016, accepted
2. Low picomolar, instrument-free visual detection of mercury and silver ions using low-cost programmable nanoprobes, Chemical Science, in press
3. Reprogrammable Multiplexed Detection of Circulating OncomiRs Using Hybridization Chain Reaction, Chemical Communications, 2016, 52, 3524-3527
4. Multiplexed activity of perAuxidase: DNA-capped AuNPs act as adjustable peroxidase, Analytical Chemistry, 2016, 88 (1), pp 600–605.
5. Locked nucleic acid-modified antisense miR-10b oligonucleotides form stable duplexes on gold nanoparticles, BioNanoScience, 4(2), 2014, 195-200.
II. Two dimensional nanoparticle and oligonucleotide assemblies for fluorogenic detection: The goal of this research direction is to engineer water-soluble two-dimensional nanosaaemblies and develop methodologies to detect circulating small RNAs and DNAs in human body fluids or cell lysates for the state-of-the art diagnostics. The development of non- or minimally invasive, cost-efficient and rapid diagnostic tools and identification of alternative disease biomarkers will have a major impact on fighting human diseases effectively. Our translational approach combines two emerging fields, the role of two dimensional nanosheets in biomedicine and circulating miRNAs and DNAs in human diseases. The proposed detection approach is simple, rapid, inexpensive, enables simultaneous detection, eliminates labor-intensive multi-step procedures, can be performed in a high-throughput fashion using simple equipment and has minimum background signal. Our goal is to fully characterize the two-dimensional nanosheets and advance 2D nanoassemblies for addressing biological and biomedical challenges.
miRNA detection using graphene and modifed nucleic acids Simultenous detection of cancer biomarkers from human body fluids External stimulus-controlled biomarker detection
Publications on topic II:
1. Complex Thermodynamic Behavior of Single-Stranded Nucleic Acid Adsorption to Graphene Surfaces, Langmuir, 2016, 32 (24), pp 6028–6034.
2. Unlocked Nucleic Acids for miRNA Detection Using Two Dimensional Nano-Graphene Oxide”, Biosensors and Bioelectronics, in press
3. Discriminating a single nucleotide difference for enhanced miRNA detection using tunable graphene and oligonucleotide nanodevices, Langmuir, 2015, 31 (36), pp 9943–9952
4. Monitoring the multitask mechanism of DNase I activity using graphene nano assemblies”, Bioconjugate Chemistry, 2015, 26 (4), pp 735–745.
5. Smart polymer functionalized graphene nano-devices for thermo-switch controlled biodetection”, ACS Biomaterials Science & Engineering, 2015, 1 (1), pp 27–36.
6. Simultaneous detection of circulating oncomiRs from body fluids for prostate cancer staging using nano-graphene oxide, ACS Applied Materials & Interfaces, 2014, 6 (17), pp 14772–14778.
7. DNA-Length-Dependent Quenching of Fluorescently Labeled Iron Oxide Nanoparticles with Gold, Graphene Oxide and MoS2 Nanostructures”, ACS Applied Materials & Interfaces, 6 (15), 2014, 12100–12110.
8. Nano-graphene oxide as a novel platform for monitoring the effect of LNA modification in nucleic acid interactions”, Analyst, 2014, 139 (4), 714 - 720
9. Doxorubicin loading on graphene oxide, iron oxide and gold nanoparticle hybrid”, Journal of Materials Chemistry B, 2013, 1 (45), 6187 - 6193
III. Image-guided sequential nanodrug activation: The goal of this “technology-development” research is to engineer nanoparticles that are responsive to non-toxic, but highly selective chemical triggers for image-guided delivery and controlled-activation of different types of therapeutic cargoes: small chemodrug molecules and functional RNA macromolecules .Nanoparticles are well-established delivery vehicles capable of shuttling molecular cargoes across different types of biological membranes. A major flaw of the standard nanoparticle assembly is lack of selective control over cargo release. Functional cargoes are typically released by environmental factors, such as pH, redox potential and ATP gradient, that cause cleavage of chemical linkers. Lack of control over this process can result in premature payload release, before the nanoparticles reached their intended target. In turn, this can lead to highly undesirable cytotoxicity and off-target affects. Our research direction for this topic aims to address this flaw using a transformative approach involving bio-orthogonal chemistry. This process can be precisely controlled and chemical design of the bio-orthogonal groups provides for flexibility of the release kinetics. The approach has potential to revolutionize the currently used nanoparticle-based delivery methods.
Ratiometric functionalization of therapeutic nanoparticles Doxorubicin prodrug activation using functional nanoparticles Nanoparticle-mediated in vivo RNA prodrug activation
Publications on topic III:
1. In situ activation of a doxorubicin prodrug using imaging-capable nanoparticles, Chemical Communications, 2016,52, 6174-6177.
2. Controlling RNA expression in cancer using iron oxide nanoparticles detectable by MRI and in vivo optical imaging, Methods Mol. Biol., 2016;1372:163-79.
3. Context-dependent differences in miR-10b breast oncogenesis can be targeted for the prevention and arrest of lymph node metastasis, Oncogene, 2013, 32(12), 1530-1538.