Yan Liu

More than 70% of cancer patients receive radiotherapy during their treatment, with consequent various side effects on normal cells due to high ionizing radiation doses despite tumor shrinkage. To date, many radioprotectors and radiosensitizers have been investigated in preclinical studies, but their use has been hampered by the high toxicity to normal cells or poor tumor radiosensitization effects. Genistein is a naturally occurring isoflavone found in soy products. It selectively sensitizes tumor cells to radiation while protecting normal cells from radiation-induced damage, thus improving the efficacy of radiotherapy and consequent therapeutic outcomes while reducing adverse effects. Genistein protects normal cells by its potent antioxidant effect that reduces oxidative stress and mitigates radiation-induced apoptosis and inflammation. Conversely, genistein increases the radiosensitivity of tumor cells through specific mechanisms such as the inhibition of DNA repair, the arrest of the cell cycle in the G₂/M phase, the generation of reactive oxygen species (ROS), and the modulation of apoptosis. These effects increase the cytotoxicity of radiation. Preclinical studies demonstrated genistein efficacy in various cancer models, such as breast, prostate, and lung cancer. Despite limited clinical studies, the existing evidence supports the potential of genistein in improving the therapeutic effect of radiotherapy. Future research should focus on dosage optimization and administration, the exploration of combination therapies, and long-term clinical trials to establish genistein benefits in clinical settings. Hence, the unique ability of genistein to improve the radiosensitivity of tumor cells while protecting normal cells could be a promising strategy to improve the efficacy and safety of radiotherapy.

Purpose To assess the value of glutamate chemical exchange saturation transfer (GluCEST) after whole-brain radiotherapy (WBRT) as an imaging marker of radiation-induced brain injury (RBI) and to preliminarily show the feasibility of multiparametric MRI-guided organ at risk (OAR) avoidance. Methods Rats were divided into two groups: the control (CTRL) group (n = 9) and the RBI group (n = 9). The rats in the RBI group were irradiated with an X‑ray radiator and then subjected to a water maze experiment 4 weeks later. In combination with high-performance liquid chromatography (HPLC), we evaluated the value of GluCEST applied to glutamate changes for RBI and investigated the effect of such changes on glutamatergic neuronal function. Results The average GluCEST values were markedly lower in the hippocampus and cerebral cortex. Positive correlations were observed between GluCEST values and regional homogeneity (ReHo) values in both the hippocampus and the cerebral cortex. HPLC showed a positive correlation with GluCEST values in the hippocampus. GluCEST values were positively correlated with spatial memory. Conclusion GluCEST MRI provides a visual assessment of glutamate changes in RBI rats for monitoring OAR cognitive toxicity reactions and may be used as a biomarker of OAR avoidance as well as metabolism to facilitate monitoring and intervention in radiation damage that occurs after radiotherapy.

Concentration plays an essential role in generating hydroxyl radicals in irradiated nanoenhancer suspensions. In this paper, we used coumarin-3-carboxylic acid as a hydroxyl radical-specific probe to investigate the hydroxyl radical production of different concentration nanodiamonds (NDs) and CeO2 NPs in phosphate-buffered saline under x-ray irradiation. NDs significantly enhanced hydroxyl radical production, and the maximum enhancement of hydroxyl radical production was observed at a concentration of 10 µg/ml, with an enhanced factor of 1.398 ± 0.262. CeO2 NPs can increase and scavenge hydroxyl radicals at different concentration ranges, with the lowest and highest enhanced factors of 0.623 ± 0.069 and 1.738 ± 0.264, respectively. We tested the hydrodynamic diameter at various concentrations to explore the concentration effect further. We found that with increasing concentration, there might be factors, such as hydroxyl radical recombination and nanoparticle agglomeration, that lead to changes in the enhancement factor. Based on the data from previous and present studies, the experimental results indicate that the concentration factor is essential for hydroxyl radical generation in nanoenhancer suspensions under ionizing radiation. We also provide possible mechanisms for enhancing hydroxyl radical production by nanoenhancers in water under ionizing radiation and the decrease in enhancement factor at high concentrations of nanoenhancers.

Optoacoustic imaging enables the measurement of tissue oxygen saturation (sO₂) and blood perfusion while being utilized for detecting tumor microenvironments. Our aim was to employ multispectral optoacoustic tomography (MSOT) to assess immediate‐early changes of hemoglobin level and sO₂ within breast tumors during diverse treatments. Mouse breast cancer models were allocated into four groups: control, everolimus (EVE), paclitaxel (PTX), and photodynamic therapy (PDT). Hemoglobin was quantified daily, as well as sO₂ and blood perfusion were verified by immunohistochemical (IHC) staining. MSOT showed a temporal window of enhanced oxygenation and improved perfusion in EVE and PTX groups, while sO₂ consistently remained below baseline in PDT. The same results were obtained for the IHC. Therefore, MSOT can monitor tumor hypoxia and indirectly reflect blood perfusion in a non‐invasive and non‐labeled way, which has the potential to monitor breast cancer progression early and enable individualized treatment in clinical practice.

Corrigendum for the article Multifunctional Nanosnowflakes for T1-T2 Double-Contrast Enhanced MRI and PAI Guided Oxygen Self-Supplementing Effective Anti-Tumor Therapy

This file shows supplementary materials and methods

Struma ovarii is a type of monodermal mature teratoma composed entirely or mainly of thyroid tissue, accounting for 1% to 3% of all ovarian teratomas and 0.3% to 1.0% of all ovarian tumors. Of which, struma ovarii with ascites and pleural effusion, called pseudo-Meigs’syndrome and raised cancer antigen-125 levels (CA 125) is even rarer. This paper reports the diagnosis and treatment of a patient of struma ovarii with pseudo-Meigs’syndrome, presenting with the clinical features of ovarian carci noma: Complex pelvic mass, gross ascites, right pleural effusion and markedly elevated serum CA 125 levels. During the operation, a cystic-solid mass about 20 cm × 10 cm × 5 cm in the right adnexa and a solid mass with the size of 3 cm × 2 cm × 0.1 cm in the left ovary were observed. She underwent right adnexectomy and resection of the left ovarian mass and histopathology revealed a mature left-sided ovarian teratoma and struma ovarii of right adnexal mass. During 1-year follow-up, the patient recovered well, tumor markers and other indicators returned to normal. The diagnosis and treatment process of this case suggests that the clinical symptoms of struma ovarii with pseudo-Meigs’syndrome are lack specificity, which is easily misdiagnosed. Clinicians should improve the understanding of this disease, enhance the awareness of early screening, and improve the level of diagnosis and treatment.

Introduction: Accurate tumor diagnosis is essential to achieve the ideal therapeutic effect. However, it is difficult to accurately diagnose cancer using a single imaging method because of the technical limitations. Multimodal imaging plays an increasingly important role in tumor treatment. Photodynamic therapy (PDT) has received widespread attention in tumor treatment due to its high specificity and controllable photocytotoxicity. Nevertheless, PDT is susceptible to tumor microenvironment (TME) hypoxia, which greatly reduces the therapeutic effect of tumor treatment. Methods: In this study, a novel multifunctional nano-snowflake probe ([email protected]₂@Ce6, UMC) for oxygen-enhanced photodynamic therapy was developed. We have fabricated the honeycomb-like MnO₂ to co-load chlorin e6 (Ce6, a photosensitizer) and ultrasmall superparamagnetic iron oxide (USPIO, T1-T2 double contrast agent). Under the high H₂O₂ level of tumor cells, UMC efficiently degraded and triggered the exposure of photosensitizers to the generated oxygen, accelerating the production of reactive oxygen species (ROS) during PDT. Moreover, the resulting USPIO and Mn²⁺ allow for MR T1-T2 imaging and transformable PAI for multimodal imaging-guided tumor therapy. Results: TEM and UV-vis spectroscopy results showed that nano-snowflake probe (UMC) was successfully synthesized, and the degradation of UMC was due to the pH/ H₂O₂ responsive properties. In vitro results indicated good uptake of UMC in 4T-1 cells, with maximal accumulation at 4 h. In vitro and in vivo experimental results showed their imaging capability for both T1-T2 MR and PA imaging, providing the potential for multimodal imaging-guided tumor therapy. Compared to the free Ce6, UMC exhibited enhanced treatment efficiency due to the production of O₂ with the assistance of 660 nm laser irradiation. In vivo experiments confirmed that UMC achieved oxygenated PDT under MR/PA imaging guidance in tumor-bearing mice and significantly inhibited tumor growth in tumor-bearing mice, exhibiting good biocompatibility and minimal side effects. Conclusion: The multimodal imaging contrast agent (UMC) not only can be used for MR and PA imaging but also has oxygen-enhanced PDT capabilities. These results suggest that UMC may have a good potential for further clinical application in the future. Graphical Abstract: