Exploiting topology-directed nanoparticle disassembly for triggered drug delivery

YesThe physical properties of cyclic and linear polymers are markedly different; however, there are few examples which exploit these differences in clinical applications. In this study, we demonstrate that self-assemblies comprised of cyclic-linear graft copolymers are significantly more stable than the equivalent linear-linear graft copolymer assemblies. This difference in stability can be exploited to allow for triggered disassembly by cleavage of just a single bond within the cyclic polymer backbone, via disulfide reduction, in the presence of intracellular levels of l-glutathione. This topological effect was exploited to demonstrate the first example of topology-controlled particle disassembly for the controlled release of an anti-cancer drug in vitro. This approach represents a markedly different strategy for controlled release from polymer nanoparticles and highlights for the first time that a change in polymer topology can be used as a trigger in the design of delivery vehicles. We propose such constructs, which demonstrate disassembly behavior upon a change in polymer topology, could find application in the targeted delivery of therapeutic agents.ERC are acknowledged for support to M.C.A., A.P.D. (grant number: 681559) and R.O.R. (grant number: 615142)

Financial Barriers and Lapses in Treatment and Care of HIV-Infected Adults in a Southern State in the United States

Antiretroviral (ARV) adherence has largely been considered from the perspective of an individual's behavior with less attention given to potential structural causes for lapses in treatment, such as the cost of medications and care. HIV medication expense is typically covered by third party payers. However, private insurance premiums and deductibles may rise, or policies terminated such as with a change in employment. Likewise, a patient's eligibility for publicly funded coverage like state AIDS Drug Assistance Programs (ADAP) or Medicaid can also be lost. We conducted a one-Time survey of a sample of 300 patients receiving HIV care at a single large academic center in the south of United States to examine lapses in HIV therapy due to financial reasons. We found that during the prior year, financial issues including medication cost or coverage led to a lapse in ARVs in 10% (n = 31) of participants. However, of the 42% (n = 125) participants who had been enrolled in ADAP at any time during the prior year, 21% (n = 26) reported an ARV lapse due to problems with ADAP or medication cost. Respondents cited ADAP's required semi-Annual renewal process and other administrative issues as the cause of ARV lapses. The median duration of missed ARVs was 2 weeks (range of <1-23 weeks). Non-HIV medication and transportation to and from clinic costs were also identified as financial burdens to care by respondents. In conclusion, although conducted at a single medical center and one state, this study suggests that a significant minority of HIV-infected patients encounter financial barriers to ARV access, and this is paradoxically more common among those enrolled in the state ADAP. Streamlining, supporting, and simplifying ADAP renewal procedures will likely reduce lapses in ARV adherence and persistence

Fabrication of crystals from single metal atoms

YesMetal nanocrystals offer new concepts for the design of nanodevices with a range of potential applications. Currently the formation of metal nanocrystals cannot be controlled at the level of individual atoms. Here we describe a new general method for the fabrication of multi-heteroatom-doped graphitic matrices decorated with very small, ångström-sized, three-dimensional (3D)-metal crystals of defined size. We irradiate boron-rich precious-metal-encapsulated self-spreading polymer micelles with electrons and produce, in real time, a doped graphitic support on which individual osmium atoms hop and migrate to form 3D-nanocrystals, as small as 15 Å in diameter, within 1 h. Crystal growth can be observed, quantified and controlled in real time. We also synthesize the first examples of mixed ruthenium–osmium 3D-nanocrystals. This technology not only allows the production of ångström-sized homo- and hetero-crystals, but also provides new experimental insight into the dynamics of nanocrystals and pathways for their assembly from single atoms.We thank the Leverhulme Trust (Early Career Fellowship No. ECF-2013-414 to NPEB), the University of Warwick (Grant No. RDF 2013-14 to NPEB), the Swiss National Science Foundation (Grant No. PA00P2_145308 to NPEB and PBNEP2_142949 to APB), the ERC (Grant No. 247450 to PJS), EPSRC (EP/G004897/1 to RKOR, and EP/F034210/1 to PJS) and Science City (AWM/ERDF) for support. We thank the Wellcome Trust (Grant No. 055663/Z/98/Z) for funding the Electron Microscopy Facility, School of Life Sciences, University of Warwick. We also thank COST Action CM1105 for stimulating discussions, Thomas Wilks for supplying the micelle image for Figure 1, and the Australian Synchrotron and the University of Monash for allocation of time on the SAXS/ WAXS beamline and funding. The 2000FX Gatan Orius digital TEM camera used in this research was funded by Science City: Creating and Characterizing Next Generation Advanced Materials, with support from Advantage West Midlands and part funded by the European Regional Development Fund

Exploiting nucleobase-containing materials : from monomers to complex morphologies using RAFT dispersion polymerization

yesThe synthesis of nucleobase-containing polymers was successfully performed by RAFT dispersion polymerization in both chloroform and 1,4-dioxane and self-assembly was induced by the polymerizations. A combination of scattering and microscopy techniques were used to characterize the morphologies. It is found that the morphologies of self-assembled nucleobase-containing polymers are solvent dependent. By varying the DP of the core-forming block, only spherical micelles with internal structures were obtained in chloroform when using only adenine-containing methacrylate or a mixture of adenine-containing methacrylate and thymine-containing methacrylate as monomers. However, higher order structures and morphology transitions were observed in 1,4-dioxane. A sphere-rod-lamella-twisted bilayer transition was observed in this study. Moreover, the kinetics of the dispersion polymerizations were studied in both solvents, suggesting a different formation mechanism in these systems.University of Warwick, Swiss National Science Foundation, EPSRC, Birmingham Science City, Advanatfe West Midlands (AWM), European Regional Development Fund (ERDF), Science City Research Alliance, Higher Education Funding Council for England (HEFCE

Search for the standard model Higgs boson in tau final states

We present a search for the standard model Higgs boson using hadronically decaying tau leptons, in 1 inverse femtobarn of data collected with the D0 detector at the Fermilab Tevatron ppbar collider. We select two final states: tau plus missing transverse energy and b jets, and tau+ tau- plus jets. These final states are sensitive to a combination of associated W/Z boson plus Higgs boson, vector boson fusion and gluon-gluon fusion production processes. The observed ratio of the combined limit on the Higgs production cross section at the 95% C.L. to the standard model expectation is 29 for a Higgs boson mass of 115 GeV.Comment: publication versio

Search for W' bosons decaying to an electron and a neutrino with the D0 detector

This Letter describes the search for a new heavy charged gauge boson W' decaying into an electron and a neutrino. The data were collected with the D0 detector at the Fermilab Tevatron proton-antiproton Collider at a center-of-mass energy of 1.96 TeV, and correspond to an integrated luminosity of about 1 inverse femtobarn. Lacking any significant excess in the data in comparison with known processes, an upper limit is set on the production cross section times branching fraction, and a W' boson with mass below 1.00 TeV can be excluded at the 95% C.L., assuming standard-model-like couplings to fermions. This result significantly improves upon previous limits, and is the most stringent to date.Comment: submitted to Phys. Rev. Let

Search for a scalar or vector particle decaying into Zgamma in ppbar collisions at sqrt(s) = 1.96 TeV

We present a search for a narrow scalar or vector resonance decaying into Zgamma with a subsequent Z decay into a pair of electrons or muons. The data for this search were collected with the D0 detector at the Fermilab Tevatron ppbar collider at a center of mass energy sqrt(s) = 1.96 TeV. Using 1.1 (1.0) fb-1 of data, we observe 49 (50) candidate events in the electron (muon) channel, in good agreement with the standard model prediction. From the combination of both channels, we derive 95% C.L. upper limits on the cross section times branching fraction (sigma x B) into Zgamma. These limits range from 0.19 (0.20) pb for a scalar (vector) resonance mass of 600 GeV/c^2 to 2.5 (3.1) pb for a mass of 140 GeV/c^2.Comment: Published by Phys. Lett.

Search for Higgs bosons decaying to tautau pairs in ppbar collisions at sqrt(s) = 1.96 TeV

We present a search for the production of neutral Higgs bosons decaying into tautau pairs in ppbar collisions at a center-of-mass energy of 1.96 TeV. The data, corresponding to an integrated luminosity of 5.4 fb-1, were collected by the D0 experiment at the Fermilab Tevatron Collider. We set upper limits at the 95% C.L. on the product of production cross section and branching ratio for a scalar resonance decaying into tautau pairs, and we then interpret these limits as limits on the production of Higgs bosons in the minimal supersymmetric standard model (MSSM) and as constraints in the MSSM parameter space.Comment: 7 pages, 5 figures, submitted to PL