122 research outputs found

    M13 Virus based detection of bacterial infections in living hosts

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    We report a first method for using M13 bacteriophage as a multifunctional scaffold for optically imaging bacterial infections in vivo. We demonstrate that M13 virus conjugated with hundreds of dye molecules (M13-Dye) can target and distinguish pathogenic infections of F- pili expressing and F -negative strains of E. coli. Further, in order to tune this M13-Dye complex suitable for targeting other strains of bacteria, we have used a 1-step reaction for creating an anti-bacterial antibody -M13-Dye probe. As an example, we show anti-S. aureus -M13-Dye able to target and image infections of S. aureus in living hosts, with a 3.7Ă— increase in fluorescence over background.National Cancer Institute (U.S.) (Center for Cancer Nanotechnology Excellence Grant 5-U54-CA151884-03

    Virus-templated Au and Au–Pt core–shell nanowires and their electrocatalytic activities for fuel cell applications

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    A facile synthetic route was developed to make Au nanowires (NWs) from surfactant-mediated bio-mineralization of a genetically engineered M13 phage with specific Au binding peptides. From the selective interaction between Au binding M13 phage and Au ions in aqueous solution, Au NWs with uniform diameter were synthesized at room temperature with yields greater than 98% without the need for size selection. The diameters of Au NWs were controlled from 10 nm to 50 nm. The Au NWs were found to be active for electrocatalytic oxidation of CO molecules for all sizes, where the activity was highly dependent on the surface facets of Au NWs. This low-temperature high yield method of preparing Au NWs was further extended to the synthesis of Au–Pt core–shell NWs with controlled coverage of Pt shell layers. Electro-catalytic studies of ethanol oxidation with different Pt loading showed enhanced activity relative to a commercial supported Pt catalyst, indicative of the dual functionality of Pt for the ethanol oxidation and Au for the anti-poisoning component of Pt. These new one-dimensional noble metal NWs with controlled compositions could facilitate the design of new alloy materials with tunable properties.United States. Army Research Office (Institute for Collaborative Biotechnologies, grant W911NF-09-0001)National Science Foundation (U.S.) (MRSEC Program, award no. DMR–0819762)Samsung (Firm) (Samsung Foundation of Culture, Samsung Scholarship

    Deep, noninvasive imaging and surgical guidance of submillimeter tumors using targeted M13-stabilized single-walled carbon nanotubes

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    Highly sensitive detection of small, deep tumors for early diagnosis and surgical interventions remains a challenge for conventional imaging modalities. Second-window near-infrared light (NIR2, 950–1,400 nm) is promising for in vivo fluorescence imaging due to deep tissue penetration and low tissue autofluorescence. With their intrinsic fluorescence in the NIR2 regime and lack of photobleaching, single-walled carbon nanotubes (SWNTs) are potentially attractive contrast agents to detect tumors. Here, targeted M13 virus-stabilized SWNTs are used to visualize deep, disseminated tumors in vivo. This targeted nanoprobe, which uses M13 to stably display both tumor-targeting peptides and an SWNT imaging probe, demonstrates excellent tumor-to-background uptake and exhibits higher signal-to-noise performance compared with visible and near-infrared (NIR1) dyes for delineating tumor nodules. Detection and excision of tumors by a gynecological surgeon improved with SWNT image guidance and led to the identification of submillimeter tumors. Collectively, these findings demonstrate the promise of targeted SWNT nanoprobes for noninvasive disease monitoring and guided surgery.National Institutes of Health (U.S.). Center for Nanotechnology Excellence (Grant U54-CA119349-04)National Institutes of Health (U.S.). Center for Nanotechnology Excellence (Grant U54-CA151884)David H. Koch Institute for Integrative Cancer Research at MIT. Frontier Research Program (Kathy and Curt Marble Cancer Research Fund)National Institute of Environmental Health Sciences (Grant P30-ES002109)Marie D. & Pierre Casimir-Lambert FundAmar G. Bose Research Gran

    Layer-by-layer assembled fluorescent probes in the second near-infrared window for systemic delivery and detection of ovarian cancer

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    Fluorescence imaging in the second near-infrared window (NIR-II, 1,000–1,700 nm) features deep tissue penetration, reduced tissue scattering, and diminishing tissue autofluorescence. Here, NIR-II fluorescent probes, including down-conversion nanoparticles, quantum dots, single-walled carbon nanotubes, and organic dyes, are constructed into biocompatible nanoparticles using the layer-by-layer (LbL) platform due to its modular and versatile nature. The LbL platform has previously been demonstrated to enable incorporation of diagnostic agents, drugs, and nucleic acids such as siRNA while providing enhanced blood plasma half-life and tumor targeting. This work carries out head-to-head comparisons of currently available NIR-II probes with identical LbL coatings with regard to their biodistribution, pharmacokinetics, and toxicities. Overall, rare-earth-based down-conversion nanoparticles demonstrate optimal biological and optical performance and are evaluated as a diagnostic probe for high-grade serous ovarian cancer, typically diagnosed at late stage. Successful detection of orthotopic ovarian tumors is achieved by in vivo NIR-II imaging and confirmed by ex vivo microscopic imaging. Collectively, these results indicate that LbL-based NIR-II probes can serve as a promising theranostic platform to effectively and noninvasively monitor the progression and treatment of serous ovarian cancer.United States. Department of Defense. Ovarian Cancer Research Program (TEAL Innovator Award OC120504)National Cancer Institute (U.S.) (Center for Cancer Nanotechnology Excellence Grant 5-U54- CA151884-03

    M13-templated magnetic nanoparticles for targeted in vivo imaging of prostate cancer

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    Molecular imaging allows clinicians to visualize the progression of tumours and obtain relevant information for patient diagnosis and treatment1. Owing to their intrinsic optical, electrical and magnetic properties, nanoparticles are promising contrast agents for imaging dynamic molecular and cellular processes such as protein–protein interactions, enzyme activity or gene expression2. Until now, nanoparticles have been engineered with targeting ligands such as antibodies and peptides to improve tumour specificity and uptake. However, excessive loading of ligands can reduce the targeting capabilities of the ligand3, 4, 5 and reduce the ability of the nanoparticle to bind to a finite number of receptors on cells6. Increasing the number of nanoparticles delivered to cells by each targeting molecule would lead to higher signal-to-noise ratios and would improve image contrast. Here, we show that M13 filamentous bacteriophage can be used as a scaffold to display targeting ligands and multiple nanoparticles for magnetic resonance imaging of cancer cells and tumours in mice. Monodisperse iron oxide magnetic nanoparticles assemble along the M13 coat, and its distal end is engineered to display a peptide that targets SPARC glycoprotein, which is overexpressed in various cancers. Compared with nanoparticles that are directly functionalized with targeting peptides, our approach improves contrast because each SPARC-targeting molecule delivers a large number of nanoparticles into the cells. Moreover, the targeting ligand and nanoparticles could be easily exchanged for others, making this platform attractive for in vivo high-throughput screening and molecular detection.National Institutes of Health (U.S.) (NIH Center for Cancer Nanotechnology Excellence U54-CA151884)National Institutes of Health (U.S.) (NIH NCI RO1 CA137071

    Engineered yeast for enhanced CO2 mineralization

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    In this work, a biologically catalysed CO2 mineralization process for the capture of CO2 from point sources was designed, constructed at a laboratory scale, and, using standard chemical process scale-up protocols, was modelled and evaluated at an industrial scale. A yeast display system in Saccharomyces cerevisae was used to screen several carbonic anhydrase isoforms and mineralization peptides for their impact on CO2 hydration, CaCO3 mineralization, and particle settling rate. Enhanced rates for each of these steps in the CaCO3 mineralization process were confirmed using quantitative techniques in lab-scale measurements. The effect of these enhanced rates on the CO2 capture cost in an industrial scale CO2 mineralization process using coal fly ash as the CaO source was evaluated. The model predicts a process using bCA2-yeast and fly ash is [similar]10% more cost effective per tonne of CO2 captured than a process with no biological molecules, a savings not realized by wild-type yeast and high-temperature stable recombinant CA2 alone or in combination. The levelized cost of electricity for a power plant using this process was calculated and scenarios in which this process compares favourably to CO2 capture by MEA absorption process are presented.MIT Energy InitiativeEni S.p.A. (Firm)National Institutes of Health (U.S.) (NIH Biotechnology Training Program)Thomas and Stacey Siebel Foundatio

    Tunable Localized Surface Plasmon-Enabled Broadband Light-Harvesting Enhancement for High-Efficiency Panchromatic Dye-Sensitized Solar Cells

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    In photovoltaic devices, light harvesting (LH) and carrier collection have opposite relations with the thickness of the photoactive layer, which imposes a fundamental compromise for the power conversion efficiency (PCE). Unbalanced LH at different wavelengths further reduces the achievable PCE. Here, we report a novel approach to broadband balanced LH and panchromatic solar energy conversion using multiple-core–shell structured oxide-metal-oxide plasmonic nanoparticles. These nanoparticles feature tunable localized surface plasmon resonance frequencies and the required thermal stability during device fabrication. By simply blending the plasmonic nanoparticles with available photoactive materials, the broadband LH of practical photovoltaic devices can be significantly enhanced. We demonstrate a panchromatic dye-sensitized solar cell with an increased PCE from 8.3% to 10.8%, mainly through plasmon-enhanced photoabsorption in the otherwise less harvested region of solar spectrum. This general and simple strategy also highlights easy fabrication, and may benefit solar cells using other photoabsorbers or other types of solar-harvesting devices.Eni-MIT Energy Initiative Founding Member ProgramNational Science Foundation (U.S.) (ECCS Award 1028568)United States. Air Force Office of Scientific Research (AFOSR MURI Award FA9550-12-1-0488
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