The universal sensor array is composed of 12 fluorescently silent non-specific artificial nanoreceptors (2D-nps) for the identification and classification of five proteins, three types of breast cancer cells and a structure-switching event of a macromolecule.
In this study, we have investigated the intrinsic peroxidase-like activity of citrate-capped AuNPs (perAuxidase) and demonstrated that the nanozyme function can be multiplexed and tuned by integrating oligonucleotides on a nanoparticle surface. Systematic studies revealed that by controlling the reaction parameters, the mutiplexing effect can be delayed or advanced and further used for aptasensor applications.
Circulating oncomiRs are highly stable diagnostic, prognostic, and therapeutic tumor biomarkers, which can reflect the status of the disease and response to cancer therapy. miR-141 is an oncomiR, which is overexpressed in advanced prostate cancer patients, whereas its expression is at the normal levels in the early stages of the disease. On the other hand, miR-21 is significantly elevated in the early stage, but not in the advanced prostate cancer. Here, we have demonstrated simultaneous detection of exogenous miR-21 and miR-141 from human body fluids including blood, urine and saliva using nanographene oxide. Our system enables us to specifically and reliably detect each oncomiR at different fluorescence emission channels from a large population of RNAs extracted from body fluids. We were also able to determine the content and the ratio of the miR-21 and miR-141 in 10 different miRNA cocktails composed of various, but unknown, concentrations of both oncomiRs. A strong agreement (around 90%) between the experimental results and the actual miRNA compositions was observed. Moreover, we have demonstrated that overexpressed miR-21 or miR-141 increases the fluorescence only at their signature wavelengths of 520 and 670 nm, respectively. The approach in this study combines two emerging fields of nanographene in biomedicine and the role of circulating miRNAs in cancer. Our strategy has the potential to address the current challenges in diagnosis, prognosis and staging of prostate cancer with a non- or minimally invasive approach.
In just over a decade since its discovery, research on graphene has exploded due to a number of potential applications in electronics, materials, and medicine. In its water-soluble form of graphene oxide, the material has shown promise as a biosensor due to its preferential absorption of single-stranded polynucleotides and fluorescence quenching properties. The rational design of these biosensors, however, requires an improved understanding of the binding thermodynamics and ultimately a predictive model of sequence-specific binding. Toward these goals, here we directly measured the binding of nucleosides and oligonucleotides to graphene oxide nanoparticles using isothermal titration calorimetry and used the results to develop molecular models of graphene-nucleic acid interactions. We found individual nucleosides binding KD values lie in the submillimolar range with binding order of rG < rA < rC < dT < rU, while 5mer and 15mer oligonucleotides had markedly higher binding affinities in the range of micromolar and submicromolar KD values, respectively. The molecular models developed here are calibrated to quantitatively reproduce the above-mentioned experimental results. For oligonucleotides, our model predicts complex binding features such as double-stacked bases and a decrease in the fraction of graphene stacked bases with increasing oligonucleotide length until plateauing beyond ∼10-15 nucleotides. These experimental and computational results set the platform for informed design of graphene-based biosensors, further increasing their potential and application.
Magnetic particle imaging (MPI) is a new imaging modality with the potential for high‐resolution imaging while retaining the noninvasive nature of other current modalities such as magnetic resonance imaging (MRI) and positron emission tomography (PET). It is able to track location and quantities of special superparamagnetic iron oxide nanoparticles without tracing any background signal. MPI utilizes the unique, intrinsic aspects of the nanoparticles: how they react in the presence of the magnetic field, and the subsequent turning off of the field. The current group of nanoparticles that are used in MPI are usually commercially available for MRI. Special MPI tracers are in development by many groups that utilize an iron‐oxide core encompassed by various coatings. These tracers would solve the current obstacles by altering the size and material of the nanoparticles to what is required by MPI. In this review, the theory behind and the development of these tracers are discussed. In addition, applications such as cell tracking, oncology imaging, neuroimaging, and vascular imaging, among others, stemming from the implementation of MPI into the standard are discussed.Level of Evidence: 5Technical Efficacy Stage: 3J. Magn. Reson. Imaging 2020;51:1659–1668.
Myelin sheath thickness is precisely regulated and essential for rapid propagation of action potentials along myelinated axons. In the peripheral nervous system, extrinsic signals from the axonal protein neuregulin 1 (NRG1) type III regulate Schwann cell fate and myelination. Here we ask if modulating NRG1 type III levels in neurons would restore myelination in a model of congenital hypomyelinating neuropathy (CHN). Using a mouse model of CHN, we improved the myelination defects by early overexpression of NRG1 type III. Surprisingly, the improvement was independent from the upregulation of
In this study, we have coupled the DNA polymerization capability of hybridization chain reaction (HCR) with the plasmonic properties of gold nanoparticles to develop a reprogrammable and multiplexed detection of three circulating oncomiRs (miR-10b, miR-21 and miR-141) dysregulated in various disease states of breast cancer. We have demonstrated that by simply changing the initiator (label-free short single stranded DNA) content of the HCR, while keeping everything else unchanged, the same nanoparticle assembly can be reprogrammed for the detection of the target oncomiRs individually or simultaneously in all possible combinations. We have shown that as little as 20 femtomoles of each oncomiR can be detected visually without using any analytical instrument. Furthermore, we demonstrated that the target oncomiR can be detected in an RNA pool isolated from a liquid biopsy mimic of breast cancer.
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