γ-Tocotrienol-Loaded Liposomes for Radioprotection from Hematopoietic Side Effects Caused by Radiotherapeutic Drugs.

With the successful development and increased use of targeted radionuclide therapy for treating cancer comes the increased risk of radiation injury to bone marrow-both direct suppression and stochastic effects, leading to neoplasia. Herein, we report a novel radioprotector drug, a liposomal formulation of γ-tocotrienol (GT3), or GT3-Nano for short, to mitigate bone marrow radiation damage during targeted radionuclide therapy. Methods: GT3 was loaded into liposomes using passive loading. 64Cu-GT3-Nano and 3H-GT3-Nano were synthesized to study the in vivo biodistribution profile of the liposome and GT3 individually. The radioprotection efficacy of GT3-Nano was assessed after acute 137Cs whole-body irradiation at a sublethal (4 Gy), a lethal (9 Gy), or a single high-dose administration of 153Sm-ethylenediamine-N,N,N',N'-tetrakis(methylene phosphonic acid) (EDTMP). Flow cytometry and fluorescence microscopy were used to analyze hematopoietic cell population dynamics and the cellular site of GT3-Nano localization in the spleen and bone marrow, respectively. Results: Bone marrow uptake and retention (percentage injected dose per gram of tissue) at 24 h was 6.98 ± 2.34 for 64Cu-GT3-Nano and 7.44 ± 2.52 for 3H-GT3-Nano. GT3-Nano administered 24 h before or after 4 Gy of total-body irradiation (TBI) promoted rapid and complete hematopoietic recovery, whereas recovery of controls stalled at 60%. GT3-Nano demonstrated dose-dependent radioprotection, achieving 90% survival at 50 mg/kg against lethal 9-Gy TBI. Flow cytometry of the bone marrow indicated that progenitor bone marrow cells MPP2 and CMP were upregulated in GT3-Nano-treated mice. Immunohistochemistry showed that GT3-Nano accumulates in CD105-positive sinusoid epithelial cells. Conclusion: GT3-Nano is highly effective in mitigating the marrow-suppressive effects of sublethal and lethal TBI in mice. GT3-Nano can facilitate rapid recovery of hematopoietic components in mice treated with the endoradiotherapeutic agent 153Sm-EDTMP.

Occurrence of organic wastewater compounds in effluent-dominated streams in Northeastern Kansas.

Fifty-nine stream-water samples and 14 municipal wastewater treatment facility (WWTF) discharge samples in Johnson County, northeastern Kansas, were analyzed for 55 compounds collectively described as organic wastewater compounds (OWCs). Stream-water samples were collected upstream, in, and downstream from WWTF discharges in urban and rural areas during base-flow conditions. The effect of secondary treatment processes on OWC occurrence was evaluated by collecting eight samples from WWTF discharges using activated sludge and six from WWTFs samples using trickling filter treatment processes. Samples collected directly from WWTF discharges contained the largest concentrations of most OWCs in this study. Samples from trickling filter discharges had significantly larger concentrations of many OWCs (p-value<0.05) compared to samples collected from activated sludge discharges. OWC concentrations decreased significantly in samples from WWTF discharges compared to stream-water samples collected from sites greater than 2000 m downstream. Upstream from WWTF discharges, base-flow samples collected in streams draining predominantly urban watersheds had significantly larger concentrations of cumulative OWCs (p-value=0.03), caffeine (p-value=0.01), and tris(2-butoxyethyl) phosphate (p-value<0.01) than those collected downstream from more rural watersheds.