PPRX-1701, a nanoparticle formulation of 6'-bromoindirubin acetoxime, improves delivery and shows efficacy in preclinical GBM models.

Derivatives of the Chinese traditional medicine indirubin have shown potential for the treatment of cancer through a range of mechanisms. This study investigates the impact of 6'-bromoindirubin-3'-acetoxime (BiA) on immunosuppressive mechanisms in glioblastoma (GBM) and evaluates the efficacy of a BiA nanoparticle formulation, PPRX-1701, in immunocompetent mouse GBM models. Transcriptomic studies reveal that BiA downregulates immune-related genes, including indoleamine 2,3-dioxygenase 1 (IDO1), a critical enzyme in the tryptophan-kynurenine-aryl hydrocarbon receptor (Trp-Kyn-AhR) immunosuppressive pathway in tumor cells. BiA blocks interferon-γ (IFNγ)-induced IDO1 protein expression in vitro and enhances T cell-mediated tumor cell killing in GBM stem-like cell co-culture models. PPRX-1701 reaches intracranial murine GBM and significantly improves survival in immunocompetent GBM models in vivo. Our results indicate that BiA improves survival in murine GBM models via effects on important immunotherapeutic targets in GBM and that it can be delivered efficiently via PPRX-1701, a nanoparticle injectable formulation of BiA.

Release of Electron Donors during Thermal Treatment of Soils.

Thermal treatment of soil and groundwater may provide an in situ source of soluble organic compounds and hydrogen (H2) that could stimulate microbial reductive dechlorination (MRD) at sites impacted by chlorinated solvents. The objectives of this study were to identify and quantify the release of electron donors and fermentable precursors during soil heating and to estimate availability of these compounds following thermal treatment. Fourteen solid materials containing <0.01 to 63.81 wt % organic carbon (OC) were incubated at 30, 60, or 90 °C for up to 180 d, leading to the release of direct electron donors (i.e., H2 and acetate) and fermentable volatile fatty acids (VFAs). Total VFA release ranged from 5 ± 0 × 10-9 carbon per gram solid (mol C/gs) during 30 °C incubation of quartz sand to 820 ± 50 × 10-6 mol C/gs during 90 °C incubation of humic acid, and was positively impacted by incubation time, temperature, and solid-phase OC content. H2 gas was detected at a maximum of 180 ± 50 × 10-9 mol H2/gs, accounting for less than 0.3% of reducing equivalents associated with VFAs released under the same conditions. These findings will allow for more reliable prediction of substrate release during thermal treatment, supporting the implementation of coupled thermal and biological remediation strategies.