Chemotherapy can induce a robust T cell antitumor immune response by triggering immunogenic cell death (ICD), a process in which tumor cells convert from nonimmunogenic to immunogenic forms. However, the antitumor immune response of ICD remains limited due to the low immunogenicity of tumor cells and the immunosuppressive tumor microenvironment. Although autophagy is involved in activating tumor immunity, the synergistic role of autophagy in ICD remains elusive and challenging. Herein, we report an autophagy amplification strategy using an ion-chelation reaction to augment chemoimmunotherapy in cancer treatments based on zinc ion (Zn²⁺)-doped, disulfiram (DSF)-loaded mesoporous silica nanoparticles (DSF@Zn-DMSNs). Upon pH-sensitive biodegradation of DSF@Zn-DMSNs, Zn²⁺ and DSF are coreleased in the mildly acidic tumor microenvironment, leading to the formation of toxic Zn²⁺ chelate through an in situ chelation reaction. Consequently, this chelate not only significantly stimulates cellular apoptosis and generates damage-associated molecular patterns (DAMPs) but also activates autophagy, which mediates the amplified release of DAMPs to enhance ICD. In vivo results demonstrated that DSF@Zn-DMSNs exhibit strong therapeutic efficacy via in situ ion chelation and possess the ability to activate autophagy, thus enhancing immunotherapy by promoting the infiltration of T cells. This study provides a smart in situ chelation strategy with tumor microenvironment-responsive autophagy amplification to achieve high tumor chemoimmunotherapy efficacy and biosafety.

Inflammatory bowel disease (IBD) is an idiopathic chronic inflammatory bowel disease characterized by inflammation, intestinal barrier injury, and imbalance of gut microbiota. Excess accumulation of reactive oxygen species (ROS) is closely correlated with the development and reoccurrence of IBD. Previous researches demonstrate that procyanidin, as a natural antioxidant, exhibits strong ability of eliminating ROS, thus showing good therapeutic effects in the inflammation-related diseases. Non-etheless, its poor stability and solubility always limits the therapeutic outcomes. Here, we typically designed an antioxidant coordination polymer nanoparticle using the engineering of procyanidin (Pc) and free iron (Fe), named Pc-Fe nanozyme, for effectively scavenging ROS and further inhibiting inflammation while altering the gut microbiome for the treatment of colitis. Furthermore, in vitro experiments uncover that Pc-Fe nanoparticles exert strong multi biomimic activities, including peroxidase, and glutathione peroxidase, for the scavenging of ROS and protecting cells from oxidative injury. In addition, the colon accumulation of Pc-Fe nanozyme effectively protects the intestinal mucosa from oxidative damage while significantly downregulates pro-inflammatory factors, repairs the intestinal barriers and alternates gut microbiome after orally administrated in sodium dextran sulfate (DSS) induced colitis mice. The results collectively illustrate that the multienzyme mimicking Pc-Fe nanozyme owns high potential for treating IBD through scavenging ROS, inhibiting inflammation, repairing gut barriers and alternating gut microbiome, which further promising its clinical translation on IBD treatment and other ROS induced intestinal diseases.

Recent advancements in sonodynamic therapy (SDT) for cancer treatment have highlighted the potential of enhancing reactive oxygen species (ROS) generation and improving therapeutic outcomes. This study introduces zinc oxide (ZnO) nanorods (NRs) in situ loaded with silver nanoparticles (ZnO@Ag NRs), designed to optimize ROS production under ultrasound irradiation and offer significant advantages in tumor specificity and biosafety. The transmission electron microscopy and elemental mapping confirmed the consistent size and monodispersed Ag nanoparticle for ZnO@Ag NR. Sonodynamic properties showed that ZnO@Ag NRs produce higher singlet oxygen and hydroxyl radicals under ultrasound. In vitro studies demonstrated excellent biocompatibility and enhanced cell-killing effects of ZnO@Ag NRs on CT-26 cells, while in vivo results confirmed its superior anti-tumor efficacy and biosafety. Furthermore, the ZnO@Ag NRs’ antibacterial properties were also confirmed, suggesting additional benefits in treating cancers associated with bacterial infections. Collectively, these findings establish ZnO@Ag NRs as a potent and safe agent for ultrasound-driven cancer therapy.

Radiation enteritis (RE) is a severe adverse reaction after abdominal and pelvic radiotherapy, with a complicated pathogenesis and no effective treatment. Although gut microbiota dysbiosis was reported to play a critical role in RE, related molecular characteristics and intervention strategies have not been extensively summarized. In this review, the mechanisms of RE, including injury to intestinal stem cells, damage to the vascular endothelium, reshaped immune microenvironment, and mucosal barrier dysfunction, are discussed. In addition, radiation-induced gut microbiota dysbiosis is characterized by decreased abundance of beneficial bacteria such as Faecalibacterium prausnitzii and Bifidobacterium bifidum, and increased abundance of detrimental bacteria such as Escherichia-Shigella and Enterococcus. Beneficial and detrimental bacteria affect the development of RE by regulating inflammatory signaling pathways such as NF-κB and JAK/STAT3, and through their metabolites such as bile acids and short-chain fatty acids. Accordingly, several microbiome-targeted therapeutic strategies, including antibiotic administration, dietary interventions, fecal microbiota transplantation, probiotic administration and engineered bacteria, have been developed to mitigate RE. However, some challenges still remain for these therapeutic strategies. The goal of this review is to highlight the crucial role of gut microbiota dysbiosis in the pathogenesis of RE, thereby accelerating the development of individualized microbial therapies against this disease.

Emerging evidence suggests dietary interventions regulate inflammatory signaling through gut microbiome modulation, yet their therapeutic potential in radiation-induced intestinal injury (RIII) remains underexplored. This study demonstrates that ketogenic diet (KD), a high-fat and low-carbohydrate dietary regimen, exerts protective effects against RIII through dual mechanisms involving microbial regulation and inflammatory pathway inhibition. Using high-salt diet (HSD) as a dietary control, KD significantly attenuated intestinal inflammation by downregulating pro-inflammatory cytokines while enhancing barrier integrity through tight junction protein upregulation in radiation-exposed murine model. 16S rDNA sequencing showed KD enriched Akkermansia and reduced Enterobacteriaceae, whereas HSD exhibited inverse patterns. Mechanistically, RNA sequencing revealed that KD uniquely suppressed the JAK2/STAT3 pathway in RIII mice. In vitro studies demonstrated that β-hydroxybutyrate, a key ketone metabolite, effectively suppressed RORγt expression and subsequent downregulation of IL-17A gene transcription via the inhibition of JAK2/STAT3 pathway, thus mitigate inflammatory damage. Fecal microbiota transplantation validated that KD-modified microbiome directly inhibited JAK2/STAT3 signaling activation, as well as the downregulation of RORγt and IL-17A. These findings establish KD as a promising dietary strategy mitigate acute RIII through synergistic modulation of gut microbiota and inflammatory signaling, providing novel insights into nutritional approaches targeting microbial-host crosstalk in radiation injury.

Oral CeLA alleviates colitis by scavenging ROS, reducing TNF-α/IL-6, restoring tight junctions and barrier integrity, and modulating the gut microbiota.