The effective and targeted treatment of resistant cancer cells presents a significant challenge. Targeting cell ferroptosis has shown remarkable efficacy against apoptosis‐resistant tumors due to their elevated iron metabolism and oxidative stress levels. However, various obstacles have limited its effectiveness. To overcome these challenges and enhance ferroptosis in cancer cells, we have developed a self‐powered photodynamic therapeutic tablet that integrates a ferroptosis inducer (FIN), imidazole ketone erastin (IKE). FINs augment the sensitivity of photodynamic therapy (PDT) by increasing oxidative stress and lipid peroxidation. Furthermore, they utilize the Fenton reaction to supplement oxygen, generating a greater amount of reactive oxygen species (ROS) during PDT. Additionally, PDT facilitates the release of iron ions from the labile iron pool (LIP), accelerating lipid peroxidation and inducing ferroptosis. In vitro and in vivo experiments have demonstrated a more than 85% tumor inhibition rate. This synergistic treatment approach not only addresses the limitations of inadequate penetration and tumor hypoxia associated with PDT but also reduces the required medication dosage. Its high efficiency and specificity towards targeted cells minimize adverse effects, presenting a novel approach to combat clinical resistance in cancer treatment.

Malignant tumors rank as a leading cause of death worldwide. Accurate diagnosis and advanced treatment options are crucial to win battle against tumors. In recent years, Cherenkov luminescence (CL) has shown its technical advantages and clinical transformation potential in many important fields, particularly in tumor diagnosis and treatment, such as tumor detection in vivo, surgical navigation, radiotherapy, photodynamic therapy, and the evaluation of therapeutic effect. In this review, we summarize the advances in CL for tumor diagnosis and treatment. We first describe the physical principles of CL and discuss the imaging techniques used in tumor diagnosis, including CL imaging, CL endoscope, and CL tomography. Then we present a broad overview of the current status of surgical resection, radiotherapy, photodynamic therapy, and tumor microenvironment monitoring using CL. Finally, we shed light on the challenges and possible solutions for tumor diagnosis and therapy using CL.

Introduction: Ulcerative colitis (UC) is a global gastrointestinal disease, which is mainly caused by both dysfunctional epithelial barrier and inflammation response. Iron is a critical fundamental element for both the maintenance of homeostasis and the mediation of inflammation in many tissues. However, the role and mechanism of iron in the phase of enteritis and the subsequent repairing phase of intestinal stem cells has not been elucidated. In this study, we aimed to explore whether and how iron depletion would affect the occurrence and outcome of experimental colitis.Methods: Iron depletion was realized by deferoxamine (DFO) at either the early stage or late stage of dextran sulfate sodium (DSS) induced experimental colitis in mice. The gross images of colons, general health, histology, barrier integrity, and qRT-PCR were performed. Meanwhile, cell culture and colonic organoids were used to examine the influence of iron depletion in vitro. Signaling pathway and inflammatory infiltration were investigated by immunostaining.Results: Iron depletion within the early stage of DSS treatment significantly inhibited the onset of the inflammatory response, maintained the integrity of the colonic epithelium, and preserved the activity of intestinal stem cells (ISCs) both in vivo and in vitro. However, both continuous iron depletion by DFO and late DFO treatment aggravated colonic injury and postponed the recovery from colitis. Early DFO-induced iron depletion was able to maintain the p-STAT3 and p-ERK1/2 signaling pathways within the colonic epithelium at the early phase of colitis, but late DFO treatment inhibited the activity of these two pathways.Discussion: Our study demonstrated that the manipulation of iron depletion by DFO might greatly affect the outcomes of experimental colitis in a phase-dependent manner, which suggests that the balance of iron metabolism might be an effective therapeutic target for the clinical treatment of IBD patients.

Triple-negative breast cancer (TNBC) is resistant to radiotherapy due to tumor hypoxia and abnormal angiogenesis, necessitating strategies to enhance therapeutic outcomes. This study evaluates the use of minibeam radiation therapy (MBRT), delivered through a novel 3D-printed collimator made of polylactic acid (PLA) and tungsten, to modulate the TNBC microenvironment and potentially overcome radioresistance. Three collimator configurations (400, 600, 800 μm beam widths) were tested. Mice received MBRT (150 Gy) or conventional radiotherapy (CRT, 7 or 15 Gy), with tumor responses assessed using histology, RNA sequencing, and immunohistochemistry. The measured beam FWHM values for the MBRT 0.4, 0.6, and 0.8 groups were 419 ± 23 μm, 575 ± 31 μm, and 798 ± 50 μm, respectively, while the CTC distances were 832 ± 25 μm, 1296 ± 21 μm, and 1651 ± 49 μm. MBRT generated stable, spatially fractionated dose distributions with high peak-to-valley ratios. Compared to CRT at equivalent valley doses, MBRT significantly reduced tumor growth, proliferation, and hypoxia while increasing necrosis. Mechanistically, MBRT downregulated HIF-1α/VEGFR signaling, alleviating hypoxia and angiogenesis, and enhanced vascular normalization via increased pericyte coverage. These findings suggest MBRT reprograms the TNBC microenvironment, supporting its potential as a radiosensitizing strategy for clinical translation.

Introduction: Butyric acid is a major gut microbiota metabolite that exhibits many biological functions, including the suppression of colorectal cancer (CRC) growth. However, previous studies have mainly been conducted using cell lines, which do not recapitulate the genuine three−dimensional spatial characteristics of CRC. In this study, we explored the therapeutic outcome and precise molecular targets of butyrate with sodium butyrate (NaB) using tumor organoids of CRC. Methods: Firstly, we examined the influence of butyrate on CRC subcutaneous allografts. And then the biological effects of butyrate were mainly determined using CRC organoids derived from KPC mice and Caco-2 cells. The morphological characteristics of butyrate-treated CRC organoids were analyzed, and multiple experimental assays were employed to determine the biological and molecular influences of butyrate. Finally, the inhibitor of HDAC2 was used to mimic the biological effects of butyrate on CRC organoids. Results: It was observed that butyrate significantly suppressed the growth of CRC allografts. Importantly, butyrate could apparently inhibit the proliferation, disrupt epithelial integrity, and induce apoptosis in CRC organoids. Transcriptomic analyses revealed that butyrate acts as an epigenetic modulator, targeting HDAC2 and selectively repressing its transcription. This led to inhibition of cyclin D1, CDK4/6, and upregulation of p21 expression, suggesting cell cycle arrest. The selective HDAC2 inhibitor similarly recapitulated the influences of butyrate on CRC organoids. Discussion: Butyrate exerts the definitive blocking effects on cell cycle progression in CRC organoids, and HDAC2 is one of the important targets. Butyrate modulates cell cycle via targeting HDAC2, constituting a novel therapeutic pathway for CRC. This study provides new evidence for gut microbial metabolites as a potential means for the prevention and treatment of colorectal cancer.

The quiescence-activation transition of cancer stem cells regulated by environmental stimuli has been shown to potentially contribute to cancer maintenance and regrowth after therapy. However, little is known about how the neoplastic niche couples with neighboring signals to control the activation of quiescent rectal cancer stem cells during radiotherapy. Lineage-tracing experiments were performed usingHopx^CreERT2;Rosa^tdTomato mice and organoids to visualize the dynamics and radioresistance ofHopx-expressing cells in vivo. BrdU pulse-chase assays and cell cycle analysis were used to identify whether Hopx⁺ stem cells were label-retaining cells (LRCs). The paracrine pro-survival effect of radiotherapy-induced dying cancer cells on neighboring Hopx⁺ quiescent stem cells was analyzed in the context of both apoptosis and necroptosis blockade. Human rectal cancer organoids and patient-derived xenografts (PDXs) were used to assess the radiotherapy-enhanced efficacy of Hopx targeting. Lineage tracing experiments revealed that Hopx⁺ quiescent stem cell subpopulation exhibited an enhanced regeneration, which functionally drove the recurrence of rectal cancer after irradiation. Mechanistically, iron released from radiotherapy-induced tumor cell death triggered a Stat3-dependent pro-survival program in neighbor-surviving Hopx⁺ quiescent stem cells. Interestingly, we demonstrated activated Hopx⁺ cancer stem cells antagonized ferroptosis that should be caused by iron-overload via the inhibition of de novo lipid synthesis. Collectively, quiescent cancer stem cells could establish a new dependency on anti-apoptotic programs in their dying neighbors. This study highlights targeting and regulating Hopx⁺ quiescent stem cells could be a promising therapeutic approach to overcome the refractoriness of human rectal cancer.