The assembly of nanomaterials using DNA can produce complex nanostructures, but the biological applications of these structures remain unexplored. Here we describe the use of DNA to control the biological delivery and elimination of inorganic nanoparticles by organizing them into colloidal superstructures. The individual nanoparticles serve as building blocks, whose size, surface chemistry, and assembly architecture dictate overall superstructure design. These superstructures interact with cells and tissues as a function of their design, but subsequently degrade into building blocks that can escape biological sequestration. We demonstrate that this strategy reduces nanoparticle retention by macrophages and improves their in vivo tumour accumulation and whole-body elimination. Superstructures can be further functionalized to carry and protect imaging or therapeutic agents against enzymatic degradation. These results suggest a new strategy to engineer nanostructure interactions with biological systems and highlight new directions in the design of biodegradable and multifunctional nanomedicine.
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Understanding the interaction of molecularly assembled nanoparticles with physiological fluids is critical to their use for in vivo delivery of drugs and contrast agents. Here, we systematically investigated the factors and mechanisms that govern the degradation of DNA on the nanoparticle surface in serum. We discovered that a higher DNA density, shorter oligonucleotides, and thicker PEG layer increased protection of DNA against serum degradation. Oligonucleotides on the surface of nanoparticles were highly resistant to DNase I endonucleases, and degradation was carried out exclusively by protein-mediated exonuclease cleavage and full-strand desorption. These results enabled the programming of the degradation rates of the DNA-assembled nanoparticle system from 0.1 to 0.7 h −1 and the engineering of superstructures that can release two different preloaded dye molecules with distinct kinetics and half-lives ranging from 3.3 to 9.8 h. This study provides a general framework for investigating the serum stability of DNA-containing nanostructures. The results advance our understanding of engineering principles for designing nanoparticle assemblies with controlled in vivo behavior and present a strategy for storage and multistage release of drugs and contrast agents that can facilitate the diagnosis and treatment of cancer and other diseases.nanoparticle assembly | DNA nanostructures | serum stability | serum resistance | controlled cargo release
The rapid and accurate detection of antimicrobial resistance is critical to limiting the spread of infections and delivering effective treatments. Here, we developed a rapid, sensitive, and simple colorimetric nanodiagnostic platform to identify disease-causing pathogens and their associated antibiotic resistance genes within 2 h. The platform can detect bacteria from different biological samples (i.e., blood, wound swabs) with or without culturing. We validated the multicomponent nucleic acid enzyme–gold nanoparticle (MNAzyme-GNP) platform by screening patients with central line associated bloodstream infections and achieved a clinical sensitivity and specificity of 86% and 100%, respectively. We detected antibiotic resistance in methicillin-resistant Staphylococcus aureus (MRSA) in patient swabs with 90% clinical sensitivity and 95% clinical specificity. Finally, we identified mecA resistance genes in uncultured nasal, groin, axilla, and wound swabs from patients with 90% clinical sensitivity and 95% clinical specificity. The simplicity and versatility for detecting bacteria and antibiotic resistance markers make our platform attractive for the broad screening of microbial pathogens.
Gas has been detected in a number of debris disk systems. This gas may have arisen from grain sublimation or grain photodesorption. It interacts with the surrounding dust grains through a number of charge and heat exchanges. Studying the chemical composition and physical state of this gas can therefore reveal much about the dust component in these debris disks. We have produced a new code, ontario, to address gas emission from dusty gas-poor disks around A-F stars. This code computes the gas ionization and thermal balance self-consistently, with particular care taken of heating/cooling mechanisms. Line emission spectra are then produced for each species (up to zinc) by statistical equilibrium calculations of the atomic/ionic energy levels. For parameters that resemble the observed β Pictoris gas disk, we find that the gas is primarily heated by photoelectric emission from dust grains, and primarily cooled through the C II 157.7 µm line emission. The gas can be heated to a temperature that is warmer than that of the dust and may in some cases reach temperature for thermal escape. The dominant cooling line, C II 157.7 µm, should be detectable by Herschel , while the O I 63.2 µm line will be too faint. We also study the dependence of the cooling line fluxes on a variety of disk parameters, in light of the much improved sensitivity to thermal line emission in the mid/far infrared and at sub-millimeter wavelengths provided by, in particular, Herschel, SOFIA, and ALMA. These new instruments will yield much new information about dusty debris disks.
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