Inflammatory bowel disease (IBD) is an autoimmune gastrointestinal disease characterized by chronic relapsing inflammation of the intestine. Excessive pyroptosis that exists in the inflamed intestine can activate damage signals and aggravate local inflammation in IBD. Here, we designed an oral pyroptosis nanoinhibitor, DXMS@CuM@PPADT@PSS (DCMP), which can target intestinal lesions, and respond to reactive oxygen species (ROS) to release active sites and drugs at the lesion. DCMP can inhibit the activation of the nucleotide-binding domain and leucine-rich repeat family pyrin domain containing 3 (NLRP3) inflammasomes by scavenging ROS, resulting in the down-regulation of gasdermin D (GSDMD) cleavage thus inhibiting pyroptosis. It also improved intestinal barrier function, decreased inflammatory cytokine levels, and increased the diversity of gut microbiota in mice with colitis. This work is believed to expand the biomedical application of nanomaterials for innate immunity modulation.

We report gold nanoparticles (AuNPs) doped iron-based metal-organic frameworks (GIM) which displays near-infrared light (NIR)-enhanced cascade nanozyme against hypoxic tumors. Due to the strong protein adsorption-induced surface passivation, AuNPs suffer from the loss of glucose oxidase (GOx) activity. However, GIM could protect the GOx-like activity of AuNPs with the satisfactory shield capability. In addition, GIM exhibited excellent photothermal conversion ability and unique NIR light-enhanced GOx-like activity, which could efficiently increase the endogenous H₂O₂ production. Meanwhile, as the produced H₂O₂ is converted by GIM into O₂ and highly toxic ⋅OH. Thus, GIM-catalyzed cascade reactions with NIR light irradiation not only offer the O₂ but also promote the reactive oxygen species (ROS) generation at tumor sites. The produced O₂ could be further applied to AuNPs catalytic oxidation of glucose and relieve hypoxic condition of tumor microenvironment (TME). As a proof-of-concept study, GIM demonstrates the admirable tumor ablation under NIR irradiation in vivo.