Reductive damage induced autophagy inhibition for tumor therapy.

Numerous therapeutic anti-tumor strategies have been developed in recent decades. However, their therapeutic efficacy is reduced by the intrinsic protective autophagy of tumors. Autophagy plays a key role in tumorigenesis and tumor treatment, in which the overproduction of reactive oxygen species (ROS) is recognized as the direct cause of protective autophagy. Only a few molecules have been employed as autophagy inhibitors in tumor therapy to reduce protective autophagy. Among them, hydroxychloroquine is the most commonly used autophagy inhibitor in clinics, but it is severely limited by its high therapeutic dose, significant toxicity, poor reversal efficacy, and nonspecific action. Herein, we demonstrate a reductive-damage strategy to enable tumor therapy by the inhibition of protective autophagy via the catalytic scavenging of ROS using porous nanorods of ceria (PN-CeO2) nanozymes as autophagy inhibitor. The antineoplastic effects of PN-CeO2 were mediated by its high reductive activity for intratumoral ROS degradation, thereby inhibiting protective autophagy and activating apoptosis by suppressing the activities of phosphatidylinositide 3-kinase/protein kinase B and p38 mitogen-activated protein kinase pathways in human cutaneous squamous cell carcinoma. Further investigation highlighted PN-CeO2 as a safe and efficient anti-tumor autophagy inhibitor. Overall, this study presents a reductive-damage strategy as a promising anti-tumor approach that catalytically inhibits autophagy and activates the intrinsic antioxidant pathways of tumor cells and also shows its potential for the therapy of other autophagy-related diseases. Electronic Supplementary Material: Supplementary material (cellular uptake of PN-CeO2, effects of PN-CeO2 on several common malignant tumor models, viability of HaCaT cells treated with PN-CeO2 at different concentrations, time-dependent body-weight curves of SCL-1 tumor-bearing nude mice, the biodistribution of Ce element in main tissues and tumors after injection of PN-CeO2, measurement of Ce element concentration in urine and feces samples, H&E-stained images of main organs, and measurement of liver and kidney function in mice after different treatment) is available in the online version of this article at 10.1007/s12274-022-5139-z.

Size-Controlled Synthesis of Pd Nanocatalysts on Defect-Engineered CeO2 for CO2 Hydrogenation.

The size effects of metal catalysts have been widely investigated to optimize their catalytic activity and selectivity. However, the size-controllable synthesis of uniform supported metal nanoparticles without surfactants and/or additives remains a great challenge. Herein, we developed a green, surfactant-free, and universal strategy to tailor the sizes of uniform Pd nanoparticles on metal oxides by an electroless chemical deposition method via defect engineering of supports. The nucleation and growth mechanism suggest a strong electrostatic interaction between the Pd precursor and low-defective CeO2 and a weak reducing capacity for low-defective CeO2, resulting in small Pd nanoparticles. Conversely, large Pd nanoparticles were formed on a highly defective CeO2 surface. Combined with various ex situ and in situ characterizations, a higher intrinsic activity of Pd for the CO2-to-CO hydrogenation was found on large Pd nanoparticles with higher electron density owing to their stronger H2 dissociation ability and H-spillover effects, as well as the larger number of oxygen vacancies generated in situ for CO2 activation under hydrogenation conditions.

Interfacial Frustrated Lewis Pairs of CeO2 Activate CO2 for Selective Tandem Transformation of Olefins and CO2 into Cyclic Carbonates.

Effective activation of CO2 is a prerequisite for efficient utilization of CO2 in organic synthesis. Precisely controlling the interfacial events of solids shows potential for activation. Herein, defect-enriched CeO2 with constructed interfacial frustrated Lewis pairs (FLPs, two adjacent Ce3+···O2-) effectively activates CO2 via the interactions between C/Lewis basic lattice O2- and the two O atoms in CO2/two adjacent Lewis acidic Ce3+ ions. Selective cyclic carbonate production from a catalytically tandem protocol of olefins and CO2 is used to demonstrate FLP-inspired CO2 activation.

Solid frustrated-Lewis-pair catalysts constructed by regulations on surface defects of porous nanorods of CeO2.

Identification on catalytic sites of heterogeneous catalysts at atomic level is important to understand catalytic mechanism. Surface engineering on defects of metal oxides can construct new active sites and regulate catalytic activity and selectivity. Here we outline the strategy by controlling surface defects of nanoceria to create the solid frustrated Lewis pair (FLP) metal oxide for efficient hydrogenation of alkenes and alkynes. Porous nanorods of ceria (PN-CeO2) with a high concentration of surface defects construct new Lewis acidic sites by two adjacent surface Ce3+. The neighbouring surface lattice oxygen as Lewis base and constructed Lewis acid create solid FLP site due to the rigid lattice of ceria, which can easily dissociate H-H bond with low activation energy of 0.17 eV.