Multifunctional nanomedicines-enabled chemodynamic-synergized multimodal tumor therapy via Fenton and Fenton-like reactions.

Chemodynamic therapy (CDT) is well-known for using the tumor microenvironment to activate the Fenton reaction or Fenton-like reaction to generate strong oxidative hydroxyl radicals for tumor-specific treatment. It is highly selective and safe, without depth limitation of tissue penetration, and shows its potential as a new green therapeutic method with great clinical application. However, the catalytic efficiency of reagents involved in the Fenton reaction is severely affected by the inherent microenvironmental limitations of tumors and the strict Fenton reaction-dependent conditions. With the increasing application of nanotechnology in the medical field, combined therapies based on different types of functional nanomaterials have opened up new avenues for the development of next-generation CDT-enhanced system. This review will comprehensively exemplify representative results of combined therapies of CDT with other antitumor therapies such as chemotherapy, phototherapy, sonodynamic therapy, radiation therapy, magnetic hyperthermia therapy, immunotherapy, starvation therapy, gas therapy, gene therapy, oncosis therapy, or a combination thereof for improving antitumor efficiency from hundreds of the latest literature, introduce strategies such as the ingenious design of nanomedicines and tumor microenvironment regulations to enhance the combination therapy, and further summarize the challenges and future perspective of CDT-based multimodal anticancer therapy.

Predicting early necrosis of colorectal liver metastases using volumetric enhancement on baseline MRI and oil deposition on post-cTACE unenhanced CT.

PURPOSE: To predict tumor necrosis after conventional TACE (cTACE) in patients with colorectal liver metastasis (CRLM) based on volumetric oil deposition on CT one day after treatment. METHODS: Thirty-four lesions in 20 men and 6 women were included in this IRB-approved HIPAA-compliant, retrospective lesion-by-lesion-based study. Semiautomatic volumetric segmentation of target lesions was performed on baseline MRI and post-treatment CT. Predicted percentage of tumor necrosis was defined as 100%-(%baseline MRI enhancement-%CT oil deposition). Necrosis on post-TACE MRI was measured after volumetric segmentation to assess the accuracy of predicting tumor necrosis. The relationship between predicted necrosis percent and post-cTACE measured necrosis percent on MRI was compared using Pearson correlation analysis. Inter-reader agreement was calculated by intraclass correlation coefficient (ICC) after using the same method. RESULTS: Patients in this cohort had a mean age of 64 ± 14 years. Mean percentage of the viable tumor on pre-cTACE venous phase MRI was 58.5% ± 23.9%. Mean oil deposition was 19.8% ± 14.6%. Mean percentage of calculated necrosis one month after cTACE was 59.2% ± 22.7% on venous phase MRI, which had a significant correlation with predicted necrotic percentage of 61.3% ± 19.3% (r = 0.89, p < 0.0001). ICC for enhancement percentage on pre-cTACE and post-cTACE venous phase MRIs were 0.93 (95% CI 0.83, 0.97) and 0.86 (95% CI 0.66, 0.94), respectively. ICC for oil deposition was 0.92 (95% CI 0.81, 0.96). CONCLUSION: Measuring oil deposition of the whole tumor on CT one day after cTACE can assist to predict post-cTACE tumor necrosis.

Discovery and biological evaluation of some (1H-1,2,3-triazol-4-yl)methoxybenzaldehyde derivatives containing an anthraquinone moiety as potent xanthine oxidase inhibitors.

A series of (1H-1,2,3-triazol-4-yl)methoxybenzaldehyde derivatives containing an anthraquinone moiety were synthesized and identified as novel xanthine oxidase inhibitors. Among them, the most promising compounds 1h and 1k were obtained with IC50 values of 0.6µM and 0.8µM, respectively, which were more than 10-fold potent compared with allopurinol. The Lineweaver-Burk plot revealed that compound 1h acted as a mixed-type xanthine oxidase inhibitor. SAR analysis showed that the benzaldehyde moiety played a more important role than the anthraquinone moiety for inhibition potency. The basis of significant inhibition of xanthine oxidase by 1h was rationalized by molecular modeling studies.