ABSTRACT
Nitric oxide (NO) is a crucial gaseous signaling molecules in regulating cardiovascular, immune, and nervous systems. Controlled and targeted NO delivery is imperative for treating cancer, inflammation, and cardiovascular diseases. Despite various enzyme-prodrug therapy (EPT) systems facilitating controlled NO release, their clinical utility is hindered by nonspecific NO release and undesired metabolic consequence. In this study, a novel EPT system is presented utilizing a cellobioside-diazeniumdiolate (Cel2-NO) prodrug, activated by an endocellulase (Cel5A-h38) derived from the rumen uncultured bacterium of Hu sheep. This system demonstrates nearly complete orthogonality, wherein Cel2-NO prodrug maintains excellent stability under endogenous enzymes. Importantly, Cel5A-h38 efficiently processes the prodrug without recognizing endogenous glycosides. The targeted drug release capability of the system is vividly illustrated through an in vivo near-infrared imaging assay. The precise NO release by this EPT system exhibits significant therapeutic potential in a mouse hindlimb ischemia model, showcasing reductions in ischemic damage, ambulatory impairment, and modulation of inflammatory responses. Concurrently, the system enhances tissue repair and promotes function recovery efficacy. The novel EPT system holds broad applicability for the controlled and targeted delivery of essential drug molecules, providing a potent tool for treating cardiovascular diseases, tumors, and inflammation-related disorders.
ABSTRACT
Polyvinyl alcohol (PVA) was used as a solid proton donor to improve the photocatalytic performance of graphitic carbon nitride (CN) for hydrogen peroxide (H2O2) production. The modified CN (CN/PVA) was prepared by mixing CN and PVA at room temperature. The H2O2 production efficiency of CN/PVA was 5.65 times higher than that of CN in pure water. Photocurrent measurement, electrochemical impedance spectroscopy (EIS), and photoluminescence (PL) analysis proved that PVA increased charge separation of CN. X-ray photoelectron spectroscopy (XPS), and Fourier-transform infrared (FTIR) analyses further suggested that PVA acted as the proton donor during H2O2 production by interacting with CN via hydrogen bonds. The combination of the charge separation enhancer and proton donor from PVA promoted the sequential two-step single-electron reduction of O2 for H2O2 production. This study paves the way for the modification of g-C3N4 with hydroxyl-containing materials as solid proton donors for photocatalytic H2O2 production.
ABSTRACT
Hydrogen peroxide photosynthesis suffers from insufficient catalytic activity due to the high energy barrier of hydrogen extraction from H2O. Herein, we report that mechanochemically synthesized keto-form anthraquinone covalent organic framework which is able to directly synthesize H2O2 (4784 µmol h-1 g-1 at λ > 400 nm) from oxygen and alkaline water (pH = 13) in the absence of any sacrificial reagents. The strong alkalinity resulted in the formation of OH-(H2O)n clusters in water, which were adsorbed on keto moieties within the framework and then dissociated into O2 and active hydrogen, because the energy barrier of hydrogen extraction was largely lowered. The produced hydrogen reacted with anthraquinone to generate anthrahydroquinone, which was subsequently oxidized by O2 to produce H2O2. This study ultimately sheds light on the importance of hydrogen extraction from H2O for H2O2 photosynthesis and demonstrates that H2O2 synthesis is achievable under alkaline conditions.