The overproduction of reactive oxygen species (ROS) is linked to inflammatory bowel disease (IBD) and causes oxidative damage to DNA, proteins, and lipids. These ROS promote the initiation and progression of ulcerative colitis (UC). This study proposes a unique concept of nanomaterials with intrinsic enzyme-like activity (nanozymes) to mediate catalytic nanotherapy for IBD. Methods : We first synthesized manganese Prussian blue nanozymes (MPBZs) with multi-enzyme activity. A dextran sulfate sodium (DSS)-induced mouse model of colitis was built. The ROS scavenging capacity and anti-inflammatory effects of the MPBZs were investigated. Results : As a proof of concept, MPBZs with multi-enzyme activity were constructed of variable valence elements (Mn and Fe) via a facile and efficient strategy. Due to the increased intestinal permeability and positively charged surfaces of inflamed mucosa in murine colitis, the prepared MPBZs with nanoscale sizes and negative charges preferentially accumulated at inflamed sites after oral administration. Importantly, MPBZs mediated catalytic nanotherapy for IBD in mice via a primary effect on the toll-like receptor signaling pathway without adverse side effects. Conclusion : MPBZs with multi-enzyme activity were constructed to treat IBD. This nanozyme-based approach is a promising strategy for catalytic nanotherapy in patients with colonic IBD.

The overproduction of reactive oxygen species (ROS) is central to the progression of inflammatory bowel disease (IBD), which may be the potential therapeutic target. Prussian blue (PB) nanoparticles with good biosafety can act as an artificial nanozyme, effectively scavenging ROS. To date, PB-based nanomaterials have not been developed and utilized for treatment of IBD. In this study, poly(vinylpyrrolidone)-modified Prussian blue (PPB) nanoparticles are constructed with good physiological stability and biosafety by a simple and efficient method. The prepared PPBs with capabilities of scavenging ROS and inhibiting proinflammatory cytokine significantly reduce colitis in mice without distinct side effects via intravenous administration. This report provides a demonstration of the protective effect of PB-based nanomedicine against IBD in living animals, offering hope and a potential alternative treatment option for patients suffering from IBD.

In this study, biocompatible Fe(III) species‐WS2‐polyvinylpyrrolidone (Fe(III) @ WS2‐PVP) nanocapsules with enhanced biodegradability and doxorubicin (DOX) loading capacity are one‐pot synthesized. In this nanocapsule, there exists a redox reaction between Fe(III) species and WS2 to form Fe2+ and WO42−. The formed Fe2+ could be oxidized to Fe3+, which reacts with Fe(III) @ WS2‐PVP again to continuously produce Fe2+ and WO42−. Such a repeated endogenous redox reaction leads to an enhanced biodegradation and DOX release of DOX @ Fe(III) @ WS2‐PVP. More strikingly, the Fe2+ generation and DOX release are further accelerated by the overexpressed H2O2 and the mild acidic tumor microenvironment (TME), since H2O2 and H+ can accelerate the oxidation of Fe2+. The continuously generated Fe2+ catalyzes a fast Fenton reaction with the innate H2O2 in tumor cells and produces abundant highly toxic hydroxyl radicals for nanocatalytic tumor therapy. Together with the high photothermal transforming capability, the DOX @ Fe(III) @WS2‐PVP nanocapsules successfully achieve the endogenous redox reaction and exogenous TME‐augmented tumor photothermal therapy, chemo and nanocatalytic therapy outcome. The concept of material design can be innovatively extended to the synthesis of biodegradable Fe(III) @ MoS2‐PVP nanocomposite, thus paving a promising novel way for the rational design of intelligent theranostic agents for highly efficient treatment of cancer.

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Although the transcription factor Krüppel-like factor 5 (KLF5) plays important roles in both inflammation and cancer, the mechanism by which this factor promotes cervical carcinogenesis remains unclear. In this study, we demonstrated a potential role for tumour necrosis factor receptor superfamily member 11a (TNFRSF11a), the corresponding gene of which is a direct binding target of KLF5, in tumour cell proliferation and invasiveness. Coexpression of KLF5 and TNFRSF11a correlated significantly with tumorigenesis in cervical tissues (P < 0.05) and manipulation of KLF5 expression positively affected TNFRSF11a mRNA and protein expression. Functionally, KLF5 promoted cancer cell proliferation, migration and invasiveness in a manner dependent partly on TNFRSF11a expression. Moreover, in vivo functional TNFRSF11a-knockdown mouse studies revealed suppression of tumorigenicity and liver metastatic potential. Notably, tumour necrosis factor (TNF)-α induced KLF5 expression by activating the p38 signalling pathway and high KLF5 and TNFRSF11a expression increased the risk of death in patients with cervical squamous cell carcinoma. Our results demonstrate that KLF5 and TNFRSF11a promote cervical cancer cell proliferation, migration and invasiveness.

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Rationale: Acute pancreatitis (AP) is a serious acute condition affecting the abdomen and shows high morbidity and mortality rates. Its global incidence has increased in recent years. Inflammation and oxidative stress are potential therapeutic targets for AP. This study was conducted to investigate the intrinsic anti-oxidative and anti-inflammatory effects of Prussian blue nanozyme (PBzyme) on AP, along with its underlying mechanism. Methods: Prussian blue nanozymes were prepared by polyvinylpyrrolidone modification method. The effect of PBzyme on inhibiting inflammation and scavenging reactive oxygen species was verified at the cellular level. The efficacy and mechanism of PBzyme for prophylactically treating AP were evaluated using the following methods: serum testing in vivo , histological scoring following hematoxylin and eosin staining, terminal deoxynucleotidyl transferase dUTP nick end labeling fluorescence staining, polymerase chain reaction array, Kyoto Encyclopedia of Genes and Genomes analysis and Western blotting analysis. Results: The synthetic PBzyme showed potent anti-oxidative and anti-inflammatory effects in reducing oxidative stress and alleviating inflammation both in vitro and in vivo in the prophylactic treatment of AP. The prophylactic therapeutic efficacy of PBzyme on AP may involve inhibition of the toll-like receptor/nuclear factor-κB signaling pathway and reactive oxygen species scavenging. Conclusion: The single-component, gram-level mass production, stable intrinsic biological activity, biosafety, and good therapeutic efficacy suggest the potential of PBzyme in the preventive treatment of AP. This study provides a foundation for the clinical application of PBzyme.