Chemodynamic therapy (CDT) is an emerging therapy method that kills cancer cells by converting intracellular hydrogen peroxide (H2O2) into highly toxic hydroxyl radicals (•OH). To overcome the current limitations of the insufficient endogenous H2O2 and the high concentration of glutathione (GSH) in tumor cells, an intelligent nanocatalytic theranostics (denoted as PGC‐DOX) that possesses both H2O2 self‐supply and GSH‐elimination properties for efficient cancer therapy is presented. This nanoplatform is constructed by a facile one‐step biomineralization method using poly(ethylene glycol)‐modified glucose oxidase (GOx) as a template to form biodegradable copper‐doped calcium phosphate nanoparticles, followed by the loading of doxorubicin (DOX). As an enzyme catalyst, GOx can effectively catalyze intracellular glucose to generate H2O2, which not only starves the tumor cells, but also supplies H2O2 for subsequent Fenton‐like reaction. Meanwhile, the redox reaction between the released Cu2+ ions and intracellular GSH will induce GSH depletion and reduce Cu2+ to Fenton agent Cu+ ions, and then trigger the H2O2 to generate •OH by a Cu+‐mediated Fenton‐like reaction, resulting in enhanced CDT efficacy. The integration of GOx‐mediated starvation therapy, H2O2 self‐supply and GSH‐elimination enhanced CDT, and DOX‐induced chemotherapy, endow the PGC‐DOX with effective tumor growth inhibition with minimal side effects in vivo.
Ferroelectrics are usually inflexible oxides that undergo brittle deformation. We synthesized freestanding single-crystalline ferroelectric barium titanate (BaTiO3) membranes with a damage-free lifting-off process. Our BaTiO3 membranes can undergo a ~180° folding during an in situ bending test, demonstrating a super-elasticity and ultraflexibility. We found that the origin of the super-elasticity was from the dynamic evolution of ferroelectric nanodomains. High stresses modulate the energy landscape markedly and allow the dipoles to rotate continuously between the a and c nanodomains. A continuous transition zone is formed to accommodate the variant strain and avoid high mismatch stress that usually causes fracture. The phenomenon should be possible in other ferroelectrics systems through domain engineering. The ultraflexible epitaxial ferroelectric membranes could enable many applications such as flexible sensors, memories, and electronic skins.
This review highlights the empirical design guidelines and photophysical property manipulation of Aza-BODIPY dyes and the latest advances in their bioapplications.
The transient receptor potential vanilloid 5 (TRPV5) channel is a member of the transient receptor potential (TRP) channel family, which is highly selective for Ca2+, that is present primarily at the apical membrane of distal tubule epithelial cells in the kidney and plays a key role in Ca2+ reabsorption. Here we present the structure of the full-length rabbit TRPV5 channel as determined using cryo-EM in complex with its inhibitor econazole. This structure reveals that econazole resides in a hydrophobic pocket analogous to that occupied by phosphatidylinositides and vanilloids in TRPV1, thus suggesting conserved mechanisms for ligand recognition and lipid binding among TRPV channels. The econazole-bound TRPV5 structure adopts a closed conformation with a distinct lower gate that occludes Ca2+ permeation through the channel. Structural comparisons between TRPV5 and other TRPV channels, complemented with molecular dynamics (MD) simulations of the econazole-bound TRPV5 structure, allowed us to gain mechanistic insight into TRPV5 channel inhibition by small molecules.
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