A cuproptosis nanocapsule for cancer radiotherapy.

Residual tumours that persist after radiotherapy often develop acquired radiation resistance, increasing the risk of recurrence and metastasis while providing obstacles to re-irradiation. Using samples from patients and experimental mice, we discovered that FDX1 and LIAS, key regulators of cuproptosis, were up-regulated in residual tumours following radiotherapy, conferring the increased sensitivity to cuproptosis. Therefore, we proposed a novel radiosensitization strategy focused on cuproptosis, using a copper-containing nanocapsule-like polyoxometalate as a paradigm. In an initial demonstration, we showed that the nanocapsule released copper ions in a controlled manner upon exposure to ionizing radiation. Furthermore, radiation-triggered cuproptosis overcame acquired radiation resistance even at clinically relevant radiation doses and activated a robust abscopal effect, with a 40% cure rate in both radioresistant and re-irradiation tumour models. Collectively, targeting cuproptosis is a compelling strategy for addressing acquired radiation resistance, optimizing the local antitumour effects of radiotherapy while simultaneously activating systemic antitumour immunity.

Lipiodol emulsion as a dual chemoradiation-sensitizer for pancreatic cancer treatment.

Pancreatic ductal adenocarcinoma (PDAC) has a low survival rate and limited treatment options. Concurrent chemoradiotherapy is considered beneficial to improve tumor control, but the low drug bioavailability at tumor site and the low radiation tolerance of surrounding healthy organs greatly limits its effectiveness. Lipiodol, a natural drug carrier used in clinical transarterial chemoembolization, has shown potential as a radiosensitizer due to its high Z element iodine composition. Thus, this study aims to repurpose lipiodol as a sensitizer to simultaneously enhance chemo- and radiotherapy for PDAC. To this end, a stable lipiodol emulsion (IOE) loaded with gemcitabine is designed using clinically approved surfactants. At in vivo level, IOE demonstrates better radiotherapeutic effect than existing nanoradiosensitizers and enhanced drug bioavailability over free drug, leading to significant tumor inhibition and improved survival rates under concurrent chemo-radiotherapy. This may due to the sustained drug release, homogenous spatial distribution, and long-term retention ability of IOE in solid PDAC tumor. Furthermore, to better understand the functioning mechanism of drug-loaded IOE, in vitro study is conducted to reveal the ROS- and DNA damage-related therapeutic pathways. Lastly, a comprehensive toxicity assessment also proves the good biocompatibility and safety of as-prepared IOE. This study offers a clinically feasible sensitizer for simultaneous chemoradiotherapy and holds potential for other types of cancer treatment in clinics.

Manipulating Radiation-Sensitive Z-DNA Conformation for Enhanced Radiotherapy.

DNA double-strand breaks (DSBs) yield highly determines radiotherapy efficacy. However, improving the inherent radiosensitivity of tumor DNA to promote radiation-induced DSBs remains a challenge. Using theoretical and experimental models, the underexplored impact of Z-DNA conformations on radiosensitivity, yielding higher DSBs than other DNA conformations, is discovered. Thereout, a radiosensitization strategy focused on inducing Z-DNA conformation, utilizing CBL@HfO2 nanocapsules loaded with a Z-DNA inducer CBL0137, is proposed. A hollow mesoporous HfO2 (HM-HfO2) acts as a delivery and an energy depositor to promote Z-DNA breakage. The nanocapsule permits the smart DSBs accelerator that triggers its radiosensitization with irradiation stimulation. Impressively, the CBL@HfO2 facilitates the B-Z DNA conformational transition, augmenting DSBs about threefold stronger than irradiation alone, generating significant tumor suppression with a 30% cure rate. The approach enables DSBs augmentation by improving the inherent radiosensitivity of DNA. As such, it opens up an era of Z-DNA conformation manipulation in radiotherapy.

Ergothioneine-Sodium Hyaluronate Dressing: A Promising Approach for Protecting against Radiation-Induced Skin Injury.

Radiotherapy commonly causes damage to healthy tissues, particularly radiation-induced skin injury (RISI) that affects a significant majority of patients undergoing radiotherapy. Effective treatments for RISI are lacking. This study focuses on the pathogenesis of RISI, which primarily involves oxidative stress. Excessive reactive oxygen species (ROS) generation during radiation induces damage to biological macromolecules, triggering oxidative stress and inflammation. To address this, ergothioneine (EGT), a natural and biocompatibile thiol compound with excellent antioxidant activity, is explored as a potential radiation-protective agent. By utilizing its specific transport and absorption in the skin tissue, as well as its efficient and stable clearance of radiation-induced "ROS storm", EGT is combined with sodium hyaluronate (NaHA) to develop a novel radiation protective dressing suitable for the skin. This EGT-NaHA dressing demonstrates an effective ability to scavenge free radicals and reduce oxidative stress in vitro and in vivo, reducing cellular apoptosis and inflammation. These results demonstrate the protective properties of EGT against RISI, with far-reaching implications for research and development in the field of radioprotection.

Tungsten-based Nanomaterials in the Biomedical Field: A Bibliometric Analysis of Research Progress and Prospects.

Tungsten-based nanomaterials (TNMs) with diverse nanostructures and unique physicochemical properties have been widely applied in the biomedical field. Although various reviews have described the application of TNMs in specific biomedical fields, there are still no comprehensive studies that summarize and analyze research trends of the field as a whole. To identify and further promote the development of biomedical TNMs, a bibliometric analysis method is used to analyze all relevant literature on this topic. First, general bibliometric distributions of the dataset by year, country, institute, referenced source, and research hotspots are recognized. Next, a comprehensive review of the subjectively recognized research hotspots in various biomedical fields, including biological sensing, anticancer treatments, antibacterials, and toxicity evaluation, is provided. Finally, the prospects and challenges of TNMs are discussed to provide a new perspective for further promoting their development in biomedical research.

Advances and applications of chiral resolution in pharmaceutical field.

The attention to chiral drugs has been raised to an unprecedented level as drug discovery and development strategies grow rapidly. However, separation of enantiomers is still a huge task, which leads to an increasing significance to equip a wider range of expertise in chiral separation science to meet the current and future challenges. In the last few decades, remarkable progress of chiral resolution has been achieved. This review summarizes and classifies chiral resolution methods in analytical scale and preparative scale systematically and comprehensively, including crystallization-based method, inclusion complexation, chromatographic separation, capillary electrophoresis, kinetic resolution, liquid-liquid extraction, membrane-based separation, and especially one bold new progress based on chiral-induced spin selectivity theory. The advances and recent applications will be presented in detail, in which the contents may bring more thinking to wide-ranging readers in various professional fields, from analytical chemistry, pharmaceutical chemistry, natural medicinal chemistry, to manufacturing of drug production.