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Background Reactive oxygen species (ROS) overproduction and excessive hypoxia play pivotal roles in the initiation and progression of ulcerative colitis (UC). Synergistic ROS scavenging and generating O2 could be a promising strategy for UC treatment. Methods Ceria nanozymes (PEG-CNPs) are fabricated using a modified reverse micelle method. We investigate hypoxia attenuating and ROS scavenging of PEG-CNPs in intestinal epithelial cells and RAW 264.7 macrophages and their effects on pro-inflammatory macrophages activation. Subsequently, we investigate the biodistribution, pharmacokinetic properties and long-term toxicity of PEG-CNPs in mice. PEG-CNPs are administered intravenously to mice with 2,4,6-trinitrobenzenesulfonic acid-induced colitis to test their colonic tissue targeting and assess their anti-inflammatory activity and mucosal healing properties in UC. Results PEG-CNPs exhibit multi-enzymatic activity that can scavenge ROS and generate O2, promote intestinal epithelial cell healing and inhibit pro-inflammatory macrophage activation, and have good biocompatibility. After intravenous administration of PEG-CNPs to colitis mice, they can enrich at the site of colonic inflammation, and reduce hypoxia-induced factor-1α expression in intestinal epithelial cells by scavenging ROS to generate O2, thus further promoting disrupted intestinal mucosal barrier restoration. Meanwhile, PEG-CNPs can effectively scavenge ROS in impaired colon tissues and relieve colonic macrophage hypoxia to suppress the pro-inflammatory macrophages activation, thereby preventing UC occurrence and development. Conclusion This study has provided a paradigm to utilize metallic nanozymes, and suggests that further materials engineering investigations could yield a facile method based on the pathological characteristics of UC for clinically managing UC. Graphical Abstract

The oxygen-consuming property of photodynamic therapy (PDT) affects its effects and aggravates tumor hypoxia, thus upregulating the vascular endothelial growth factor (VEGF) to exacerbate tumor metastasis and lead to treatment failure. Therefore, it is necessary to monitor the dynamic changes in the factors related to PDT and tumor development trends in real time, thus helping to improve PDT efficiency. This study fabricated a fluorescent probe, TPE-2HPro, and a fluorescein-labeled aptamer probe, FAM-AptamerVEGF, to detect hydrogen peroxide (H2O2) and VEGF through the photoinduced electron-transfer effect and the specific affinity of the aptamer to VEGF, respectively. The two probes were loaded into the inner pores and absorbed on the surface of polydopamine coating-wrapped mesoporous silica nanoparticles (MSN@PDA) to construct the dual-probe-loaded system, MSNTH@PDAApt, which was kept stable in fetal bovine serum (FBS) solution and achieved pH-responsive release behavior, thus helping to increase the accumulation of the two probes in tumor cells. The dichloroacetic acid-mediated in vitro antitumor tests showed that the changing trends of H2O2 and VEGF levels were consistent with the results of related mechanism studies and could be monitored by MSNTH@PDAApt. The in vitro chlorin e6 (Ce6)-mediated PDT treatment demonstrated that when the illumination condition was 650 nm, 50 mW/cm2 for 10 min, cells were more inclined to metastasis and invasion rather than death due to a substantial increase in VEGF expression at the low Ce6 concentrations. With the increase of the Ce6 concentration, the growth of the H2O2 level gradually exceeded that of VEGF, and the reactive oxygen species (ROS)-mediated cell death dominated when the Ce6 concentration was about 2 times its IC50 values. Besides, hypoxia also affected the H2O2 and VEGF changes. These results demonstrated that MSNTH@PDAApt could precisely monitor and assess the tumor development trends during PDT treatment, thus helping improve the treatment effect.

Dexamethasone (DEX) is widely used in the treatment of rheumatoid arthritis (RA), however serious side effects will be generated after long-term use of it. In this study, a nanotheranostic agent (HCPC/DEX NPs) was designed to improve the therapeutic effect of RA. HCPC/DEX NPs can responsively release drug in the presence of H2O2 and acidic condition, and can prevent drug from excessively leaking in neutral environment. Under the action of hyaluronic acid, HCPC NPs can be selectively taken up by activated macrophages and then release drug in cells. After intravenous administration, HCPC/DEX NPs can be accumulated in adjuvant-induced arthritis (AA) rat joints, and showed better RA treatment effect compared with DEX. HCPC/DEX NPs can effectively alleviate paw swelling, repaire cartilage injury, and reduce inflammatory cell infiltration and proinflammatory cytokines secretion in AA rats. And HCPC/DEX NPs caused no side effects on main organs of normal rats. Our research indicated that HCPC/DEX NPs is an effective and safe RA theranostic agent and has potential application prospects in enhanced RA treatment.

Background Reactive oxygen species (ROS) overproduction and excessive hypoxia play pivotal roles in the initiation and progression of ulcerative colitis (UC). Synergistic ROS scavenging and generating O2 could be a promising strategy for UC treatment. Methods Ceria nanozymes (CNPs) are fabricated using a modified reverse micelle method. We investigate hypoxia attenuating and ROS scavenging of CNPs in intestinal epithelial cells and RAW 264.7 macrophages. We also study the effect of CNPs on pro-inflammatory macrophages activation. Colitis mice induced by administration of 2,4,6-trinitrobenzenesulfonic acid are then given intravenous injection of CNPs to evaluate anti-inflammatory activities, mucosal healing properties and biosafety in UC. Results CNPs with multi-enzymatic activity can synergistically scavenge ROS and generate O2 to treat UC by restoring dysregulated intestinal barriers and inhibiting the pro-inflammatory macrophages activation. CNPs are found to reduce hypoxia-induced factor-1α expression in intestinal epithelial cells by generating O2 based on catalase-mimicking activity, thus further promoting disrupted intestinal mucosal barrier restoration. Meanwhile, CNPs can effectively relieve colonic macrophage hypoxia and scavenge ROS in impaired colon tissues to suppress the pro-inflammatory macrophages activation, thereby preventing UC occurrence and development. Conclusion This study has provided a paradigm to utilize metallic nanozymes, and suggests that further materials engineering investigations could yield a facile method based on the pathological characteristics of UC for clinically managing UC.