Dual Targeting of Hypoxic and Acidic Tumor Environments with a Cobalt(III) Chaperone Complex

The rational design of prodrugs for selective accumulation and activation in tumor microenvironments is one of the most promising strategies for minimizing the toxicity of anticancer drugs. Manipulation of the charge of the prodrug represents a potential mechanism to selectively deliver the prodrug to the acidic tumor microenvironment. Here we present delivery of a fluorescent coumarin using a cobalt­(III) chaperone to target hypoxic regions, and charged ligands for pH selectivity. Protonation or deprotonation of the complexes over a physiologically relevant pH range resulted in pH dependent accumulation of the fluorophore in colon cancer cells. Furthermore, in a spheroid solid tumor model, the anionic complexes exhibited preferential release of the fluorophore in the acidic/hypoxic region. By fine-tuning the physicochemical properties of the cobalt–chaperone moiety, we have demonstrated selective drug release in the acidic and hypoxic tumor microenvironment

Open burning and open detonation PM₁₀ mass emission factor measurements with optical remote sensing

<div><p>Emission factors (EFs) of particulate matter with aerodynamic diameter ≤10 µm (PM₁₀) from the open burning/open detonation (OB/OD) of energetic materials were measured using a hybrid-optical remote sensing (hybrid-ORS) method. This method is based on the measurement of range-resolved PM backscattering values with a micropulse light detection and ranging (LIDAR; MPL) device. Field measurements were completed during March 2010 at Tooele Army Depot, Utah, which is an arid continental site. PM₁₀ EFs were quantified for OB of M1 propellant and OD of 2,4,6-trinitrotoluene (TNT). EFs from this study are compared with previous OB/OD measurements reported in the literature that have been determined with point measurements either in enclosed or ambient environments, and with concurrent airborne point measurements. PM₁₀ mass EFs, determined with the hybrid-ORS method, were 7.8 × 10⁻³ kg PM₁₀/kg M1 from OB of M1 propellant, and 0.20 kg PM₁₀/kg TNT from OD of TNT. Compared with previous results reported in the literature, the hybrid-ORS method EFs were 13% larger for OB and 174% larger for OD. Compared with the concurrent airborne measurements, EF values from the hybrid-ORS method were 37% larger for OB and 54% larger for OD. For TNT, no statistically significant differences were observed for the EFs measured during the detonation of 22.7 and 45.4 kg of TNT, supporting that the total amount of detonated mass in this mass range does not have an effect on the EFs for OD of TNT.</p> <p></p><p>Implications:</p><p> <i>Particulate matter (PM) in the atmosphere affects the health of humans and ecosystems, visibility, and climate. Fugitive PM emissions are not well characterized because of spatial and temporal ubiquity and heterogeneity. The hybrid-ORS method is appropriate for quantifying fugitive PM emission factors (EFs) because it captures the spatial and temporal dispersion of ground level and elevated plumes in real time, without requiring numerous point measurement devices. The method can be applied to provide an opportunity to reduce the uncertainty of fugitive PM EFs and readily update PM emissions in National Emission Inventories for a range of fugitive PM sources.</i></p> <p></p></div