Resulting from harsh hypoxic environmental conditions, central cells in the core of solid tumors are usually more aggressive and malignant with a less stable genome. Therefore, therapeutic agents with improved penetration for the activation of immunity in tumor centers exhibit promising potential in immunotherapies. Here, polydopamine-coated Escherichia coli Nissle 1917 (EcN) bearing chlorin e6 (Ce6)-loaded and polyethyleneimine (PEI)-coated hollow manganese dioxide (shorted as EP-ChP) are applied for enhanced immunotherapy in deep tumors. After accumulation in tumor center through hypoxia targeting, manganese dioxide is degradated under the tumor microenvironment with released Ce6 and thus generates reactive oxygen species (ROS) upon 660 nm laser irradiation, which can further lower thermal-resistance of cancer cells via HSP90α downregulation. Owing to that, heating induced by polydopamine upon 808 nm laser irradiation can achieve effective tumor ablation. Phototherapy upon dual laser induces enhanced immunogenic cell death, while bacterial infections in tumor tissues also trigger innate immunity. This bacteria-based approach provides enhanced antitumor immune responses in deep tumors with great potential in the reshaping of immunosuppression tumor microenvironment.

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.