Mangiferin functionalized radioactive gold nanoparticles (MGF-198AuNPs) in prostate tumor therapy: green nanotechnology for production, in vivo tumor retention and evaluation of therapeutic efficacy.

We report here an innovative feature of green nanotechnology-focused work showing that mangiferin-a glucose functionalized xanthonoid, found in abundance in mango peels-serves dual roles of chemical reduction and in situ encapsulation, to produce gold nanoparticles with optimum in vivo stability and tumor specific characteristics. The interaction of mangiferin with a Au-198 gold precursor affords MGF-198AuNPs as the beta emissions of Au-198 provide unique advantages for tumor therapy while gamma rays are used for the quantitative estimation of gold within the tumors and various organs. The laminin receptor specificity of mangiferin affords specific accumulation of therapeutic payloads of this new therapeutic agent within prostate tumors (PC-3) of human prostate tumor origin induced in mice which overexpress this receptor subtype. Detailed in vivo therapeutic efficacy studies, through the intratumoral delivery of MGF-198AuNPs, show the retention of over 80% of the injected dose (ID) in prostate tumors up to 24 h. By three weeks post treatment, tumor volumes of the treated group of animals showed an over 5 fold reduction as compared to the control saline group. New opportunities for green nanotechnology and a new paradigm of using mangiferin as a tumor targeting agent in oncology for the application of MGF-198AuNPs in the treatment of cancer are discussed.

Albuterol metered dose inhaler performance under hyperbaric pressures.

The weight change per actuation and aerosol particle size and number delivered by albuterol metered dose inhalers (MDIs) were measured in a multiplace hyperbaric chamber at pressures ranging from one atmosphere absolute (1 ATA, 0 feet of seawater, fsw, 101 kPa) to three ATA (66 fsw, 304 kPa). Weight change per actuation by CFC (chlorofluorocarbon) and long canister HFA (hydrofluoroalkane) powered MDIs was 13 +/- 1% and 12 +/- 1% less, respectively, at 3 ATA compared to 1 ATA. However, weight change per actuation by short canister HFA MDIs was not significantly changed with pressure. The geometric mean diameters of nano particles from the CFC and short canister HFA MDIs decreased from 50 nm at 0 fsw to 32 nm at 66 fsw whereas the long canister HFA aerosol diameters were not affected. The numbers of nanometer size particles delivered at 66 fsw were only 4-7% of those delivered at 0 fsw for the CFC and long canister HFA MDIs whereas for the short canister MDIs it was 26%. We conclude that the weight change per actuation of albuterol and the sizes and numbers of aerosol particles emitted from albuterol MDIs actuated in a hyperbaric environment vary by canister type.

Sticking coefficient-orchestrated selection in a kinetic model for the first origin.

The mathematical formalism of the steady-state Poisson equation is applied to a variant of Freeman Dyson's "Toy Model" for a first origin. Our kinetic approach allows for an examination of the requisite conditions under which metabolism is quantized into discrete eigenstates (e.g. Dyson's disordered, saddle point, and metabolically active toy cell states). The surface reaction machinery additionally allows for more realistic modeling, whence the crucial role of sticking coefficients (catalyst precursors) as prebiotic selectors emerges. In our interior source model, a steady influx of vent nutrients fuels the intracellular synthesis of (impermeable) monomers within a rock-encradled cavity. Random adsorptions and desorptions occur at inactive "cell" wall sites (where the inert monomers remain impermeable until their eventual return to the intracellular metabolite pool). Occasionally, metabolizing reactions also occur due to endogeneous source monomers adsorbing at their "active" sites. Dyson's mean field approach is used to simplify the species-specific sticking coefficients at empty active (substrate) sites to functions of the fraction x of sites occupied by (catalytically) active monomers. In short, our work suggests that disorder-order transition models based on random drift between discrete metabolic eigenstates (Dyson's Toy Model) do not, in general, extend to more realistic metabolisms. From a perspective based on quasi-random feedback kinetics, the contraindication for discretization (spontaneous generation) in non-autocatalytic metabolisms is consistent with the emergence of ordered metabolism under hydrothermal driving forces, a provisio the occurrence of each period of vent dormancy coincides with a discrete zero-source (dormant) metabolic state. Cell drift to higher order is induced by the random reactions which happen to enhance the substrate specificity (chemical selectivity) of the sticking coefficients for active monomers. The result is stronger sink effects for metabolizing species, whence active adsorptions are promoted in favor of inactive adsorptions at substrate sites. Positive feedback plays a crucial role in preserving ("propagating") order in the cell wall reaction kinetics and is held in check by negative feedback inhibition of excessive cell growth. Finally, the eventual desorption of randomly growing dysfunctional proteins is postulated as a deterrent to deterioration catastrophes.

Adsorption on Heterogeneous Regular Surfaces.

Quantifying the role of surface shape and physicochemical surface conditions on the interfacial reactivity of particles and substrates is fundamental to a multitude of natural and engineered surface adsorption phenomena. We consider continuum/jump regime adsorption at the gas or liquid interface of arbitrary regular solid surfaces with heterogeneous surface features. In particular, the 3-D boundary value problem (based on Laplace's diffusion equation) is converted into a 2-D integral equation for the adsorbate concentration at the particle surface. This accommodates numerical descretization via the implementation of 2-D Gauss-Legendre quadratures on an arrangement of high- and low-adsorption patch trace sites constructed to completely cover the particle surface. A generalized computer program is developed to solve the resulting linear algebra problem for the unkown local adsorption current densities. We investigate the role of various distributions of high- and low-adsorption sites for a generalized class of spheres which includes the DNA-like shaped twisted spheres. The biological implications of the role of surface curvature on interfacial adsorption/reactivity at particle surfaces are also discussed. Copyright 2001 Academic Press.

Deposition patterns of molecular phase radon progeny (218Po) in lung bifurcations.

Indoor air contamination by radon and its decay products is currently the focus of considerable attention and is considered by many to be the greatest potential cause of lung cancer in the human environment next to smoking. The bifurcations of the human respiratory tract are regions in which enhanced local deposition of particles (hot spots) can occur. These hot spots are important in estimating the risk from radon exposure but existing mathematical models do not characterize them accurately. In this study, radon progeny in the molecular size range were sampled through an aluminium model of a lung bifurcation. The parent and secondary tube diameters used correspond to the third and fourth generations in Weibel's lung model. Steady state, nominally laminar flows were used in the study. Deposition was measured along the inside, outside, top, and bottom walls of the secondary tubes. Experimental results indicate that the deposition along the inside wall is noticeably higher than that along the other walls. The results also show that along the inside, top, and bottom walls the deposition has its overall maximum at the carina. Other maxima are also observed along the secondary tubes downstream from the carina.

Production of spherical ZrO2-Y2O3 and ZnO particles.

In recent years substantial effort has been focused on the use of engineered ceramics for biomedical applications. To produce ceramic components with reliable and reproducible properties for such speciality applications, it is necessary to use high-purity raw material powders with specific properties. Fine ceramic particles having specific shapes and sizes are also required for conducting biocompatibility experiments. This article reports on the laboratory scale production, in an aerosol reactor, of spherical, submicron zirconia (partially stabilized by yttria; ZrO2-Y2O3) and zinc oxide (ZnO) particles by the thermal decomposition of mists generated from aqueous solutions of inorganic metal salt precursors. The particles produced were characterized by scanning electron microscopy, X-ray diffraction, and Fourier transform infrared spectroscopy.

Computational flow and aerosol concentration profiles in lung bifurcations.

Flows in lung bifurcations are complicated by geometry, and it is recognized that accurate lung dosimetric models require realistic calculations of the flow and particle deposition patterns. A computational fluid dynamics study of flow and particle concentration has been carried out for a lung bifurcation based on the model developed by Weibel. The predicted flow patterns match well with previously reported experimental data. Secondary flow patterns and locations close to the walls having high particle concentrations are clearly seen.

Calculation of radiation dose at a bone-to-marrow interface using Monte Carlo modeling techniques (EGS4)

Radiation dose rate profiles at a bone-to-marrow interface were calculated by simulating a uniform radiation source at the center of the endosteal layer in a long bone. Isotopes (153Sm, 186Re, and 166Ho) were assumed to assimilate as surface agents and the dose profiles were calculated on a microscopic scale using the Electron-Gamma Shower (EGS4) computer program. We validated our computational model against published dose factors (delta) for uniform volume distributed sources replicating them to an accuracy of better than 95%. The calculated dose distributions illustrate the relative contribution of atomic electrons, beta, and photon fractions. The backscatter contribution to marrow dose increased from 3% to 4% at the source to 6% to 8% at a marrow depth of 100 microns. Backscattered dose fraction was not significantly different among the three isotopes. The dose contribution from the three isotopes was remarkably similar at ranges between 25 and 125 microns.