A drug-free nanozyme for mitigating oxidative stress and inflammatory bowel disease

Abstract

Inflammatory bowel disease (IBD) is an incurable disease of the gastrointestinal tract with a lack of effective therapeutic strategies. The proinflammatory microenvironment plays a significant role in both amplifying and sustaining inflammation during IBD progression. Herein, biocompatible drug-free ceria nanoparticles (CeNP-PEG) with regenerable scavenging activities against multiple reactive oxygen species (ROS) were developed. CeNP-PEG exerted therapeutic effect in dextran sulfate sodium (DSS)-induced colitis murine model, evidenced by corrected the disease activity index, restrained colon length shortening, improved intestinal permeability and restored the colonic epithelium disruption. CeNP-PEG ameliorated the proinflammatory microenvironment by persistently scavenging ROS, down-regulating the levels of multiple proinflammatory cytokines, restraining the proinflammatory profile of macrophages and Th1/Th17 response. The underlying mechanism may involve restraining the co-activation of NF-κB and JAK2/STAT3 pathways. In summary, this work demonstrates an effective strategy for IBD treatment by ameliorating the self-perpetuating proinflammatory microenvironment, which offers a new avenue in the treatment of inflammation-related diseases. Graphical Abstract

Immunotoxicity of metal and metal oxide nanoparticles: from toxic mechanisms to metabolism and outcomes

“…Exposure to Al 2 O 3 NPs leads to the phosphorylation of STAT3 and inhibition of PTPN6, eventually leading to the increased expression of the apoptosis marker PDCD4 [56] . In line with these findings, Zeng F. et al reported that cerium oxide NPs (CENPPEG) may downregulate ROS and numerous pro-inflammatory cytokines by inhibiting NF-κB and the JAK2/STAT3 signalling pathways, thereby countering the pro-inflammatory microenvironment and inhibiting the pro-inflammatory actions of macrophages and the Th1/Th17 response [57] , which highlights their potential anti-inflammatory effect.…”

Structure design mechanisms and inflammatory disease applications of nanozymes

“…145 Therefore, eradicating ROS may have great potential for ameliorating the pro-inflammatory microenvironment and promoting mucosal healing in IBD so as to treat UC or CD. 30 Nanozymes, as a kind of nanomaterial with multiple enzyme-like activities, are characterized by their ability to eliminate reactive oxygen species and relieve oxidative stress (Table 2).…”

“…and inhibiting their activation, to achieve further anti-inflammation effects. [27][28][29][30] Hence, utilizing nanozymes as a 'drug' for these inflammatory diseases is feasible and has great potential for clinical translation.…”

“…Zeng et al synthesized biocompatible drug-free ceria nanoparticles (CeNP-PEG) with CAT-like and SOD-like activities, and • OH scavenging abilities. 30 CeNP-PEG ameliorated the proinflammatory microenvironment via persistently scavenging ROS, down-regulating the levels of several proinflammatory cytokines, and restraining the proinflammatory profile of macrophages and Th1/Th17 response. The mechanism may be related to the inhibition of the co-activation of NF-κB and JAK2/STAT3 pathways.…”

Nanozyme-Based Remodeling of Disease Microenvironments for Disease Prevention and Treatment: A Review

“…106 Polyethylene glycol (PEG) is a synthetic polymer that is widely used for the modification of drugs to improve their physicochemical properties and biocompatibility. Zeng et al 108 prepared PEG-modified CeO 2 nanozymes for the treatment of inflammatory bowel disease, and the modified nanozymes had better biocompatibility (Figure 2A). Nie et al 109 proposed a modified PEG modification strategy for nanozymes.…”