Glucosamine-Modified Reduction-Responsive Polymeric Micelles for Liver Cancer Therapy

In this work, glucose transporter-1 (GLUT-1) and glutathione (GSH) over-expression in liver cancer was utilized to design a reduction-responsive and active targeting drug delivery system AG-PEG-SS-PCL (APSP) for the delivery of sorafenib (SF). The SF-APSP micelles were prepared using the thin film hydration method and characterized by various techniques. In vitro release experiments showed that the cumulative release of SF-APSP micelles in the simulated tumor microenvironment (pH 7.4 with GSH) reached 94.76 ± 1.78% at 48 h, while it was only 20.32 ± 1.67% in the normal physiological environment (pH 7.4 without GSH). The in vitro study revealed that glucosamine (AG) enhanced the antitumor effects of SF, and SF-APSP micelles inhibited proliferation by targeting HepG2 cells and suppressing cyclin D1 expression. The in vivo antitumor efficacy study further confirmed that the SF-APSP micelles had excellent antitumor effects and better tolerance against nude mouse with HepG2 cells than other treatment groups. All in all, these results indicated that SF-APSP micelles could be a promising drug delivery system for anti-hepatoma treatment

Hexamethylene amiloride synergizes with venetoclax to induce lysosome-dependent cell death in acute myeloid leukemia

Summary: Tumors maintain an alkaline intracellular environment to enable rapid growth. The proton exporter NHE1 participates in maintenance of this pH gradient. However, whether targeting NHE1 could inhibit the growth of tumor cells remains unknown. Here, we report that the NHE1 inhibitor Hexamethylene amiloride (HA) efficiently suppresses the growth of AML cell lines. Moreover, HA combined with venetoclax synergized to efficiently inhibit the growth of AML cells. Interestingly, lysosomes are the main contributors to the synergism of HA and venetoclax in inhibiting AML cells. Most importantly, the combination of HA and venetoclax also had prominent anti-leukemia effects in both xenograft models and bone marrow samples from AML patients. In summary, our results provide evidence that the NHE1 inhibitor HA or its combination with venetoclax efficiently inhibits the growth of AML in vitro and in vivo

Large-scale assembly of isotropic nanofiber aerogels based on columnar-equiaxed crystal transition

Abstract Ice-templating technology holds great potential to construct industrial porous materials from nanometers to the macroscopic scale for tailoring thermal, electronic, or acoustic transport. Herein, we describe a general ice-templating technology through freezing the material on a rotating cryogenic drum surface, crushing it, and then re-casting the nanofiber slurry. Through decoupling the ice nucleation and growth processes, we achieved the columnar-equiaxed crystal transition in the freezing procedure. The highly random stacking and integrating of equiaxed ice crystals can organize nanofibers into thousands of repeating microscale units with a tortuous channel topology. Owing to the spatially well-defined isotropic structure, the obtained Al2O3·SiO2 nanofiber aerogels exhibit ultralow thermal conductivity, superelasticity, good damage tolerance, and fatigue resistance. These features, together with their natural stability up to 1200 °C, make them highly robust for thermal insulation under extreme thermomechanical environments. Cascading thermal runaway propagation in a high-capacity lithium-ion battery module consisting of LiNi0.8Co0.1Mn0.1O2 cathode, with ultrahigh thermal shock power of 215 kW, can be completely prevented by a thin nanofiber aerogel layer. These findings not only establish a general production route for nanomaterial assemblies that is conventionally challenging, but also demonstrate a high-energy-density battery module configuration with a high safety standard that is critical for practical applications