No abstract

Research data are not shared.

Integrating chemodynamic therapy (CDT) and photodynamic therapy (PDT) into one nanoplatform can produce much more reactive oxygen species (ROS) for tumor therapy. Nevertheless, it is still a great challenge to selectively generate sufficient ROS in tumor regions. Meanwhile, CDT and PDT are restricted by insufficient H 2 O 2 content in the tumor as well as by the limited tumor tissue penetration of the light source. In this study, a smart pH/ROS-responsive nanoplatform, Fe 2+ @UCM-BBD, is rationally designed for tumor combination therapy. The acidic microenvironment can induce the pH-responsive release of doxorubicin (DOX), which can induce tumor apoptosis through DNA damage. Beyond that, DOX can promote the production of H 2 O 2 , providing sufficient materials for CDT. Of note, upconversion nanoparticles at the core can convert the 980 nm light to red and green light, which are used to activate Ce6 to produce singlet oxygen ( 1 O 2 ) and achieve upconversion luminescence imaging, respectively. Then, the ROS-responsive linker bis-(alkylthio)alkene is cleaved by 1 O 2 , resulting in the release of Fenton reagent (Fe 2+ ) to realize CDT. Taken together, Fe 2+ @UCM-BBD exhibits on-demand therapeutic reagent release capability, excellent biocompatibility, and remarkable tumor inhibition ability via synergistic chemo/photodynamic/chemodynamic combination therapy.

No abstract

No abstract

A molecular inhibitor of tau protein aggregation offers an attractive therapeutic possibility as disease-modifying treatment of Alzheimer’s disease. However, the ineffectiveness as well as adjoint toxicity due to superficial understanding of the inhibition mechanism has hindered drug development. Conventional approaches for screening drug ligands rely on compatible docking with the well-defined structure of a protein receptor. Therefore, the design of tau aggregation inhibitors has been inevitably hindered by the unstructured, highly dynamic nature of the tau protein. This paper suggested a new strategy for reducing tau aggregation through a dynamic process of conformational isomerization. A group of glucose gallate derivatives were selected as tau aggregation inhibitors. These star-shaped molecules have a biocompatible glucose core surrounded by several gallic acid polyphenol arms, which can bind to peptide chains at different sites, probably through hydrogen bonds and π–π stacking. Theoretically, by elevating the saddle point on the potential energy surfaces (PES) of proteins, the barrier in the dynamic pathway of peptide isomerization, glucose gallates effectively inhibit tau aggregation through a dynamic mechanism. A tau cell model based on human neurons was constructed. For the first time, we confirmed that the moderate thermodynamic binding of the molecular ligand to the tau peptide chain can not only prevent the isomerization of the peptide chain leading to aggregation but also avoid toxicity resulting from the dissociation of tau from microtubules.

No abstract

Combination of chemotherapy and phototherapy has been proposed as one promising treatment of esophageal cancer (EC). Irinotecan as a first-line treatment option is widely prescribed for metastatic EC, however, its...