Duo Yu

Radiotherapy plays a pivotal role in the management of nonsmall-cell lung cancer (NSCLC), particularly for patients who are not candidates for surgical intervention. Despite its significance, the issue of radioresistance remains a substantial challenge in the treatment of the NSCLC. Therefore, it is crucial to uncover new targets to enhance radiotherapy and investigate the mechanisms underlying radioresistance. Cuproptosis, as an emerging form of cell death dependent on intracellular copper (Cu) ions, remains unclear in its role in radioresistant NSCLCs. This study investigates the development of radioresistant NSCLC models, focusing on the role of the FOS-like antigen 1 (FOSL1) as a significant factor in mediating radioresistance. The FOSL1 gene is downregulated in radioresistant cells. Overexpression of FOSL1 induces mitochondrial damage and dysfunction, causing cuproptosis in radioresistant cells. To tackle the challenge of radioresistance in NSCLC, we propose an innovative nanostrategy focused on cuproptosis, aiming to enhance the efficacy of radiotherapy specifically in radioresistant NSCLC. This intervention could significantly enhance an increase in intracellular Cu2+ concentration and glutathione depletion while also increasing irradiation (IR)-induced oxidative stress and mitochondrial damage. The resulting mitochondrial dysfunction leads to tricarboxylic acid cycle disruption and Fe–S cluster protein destabilization. These cumulative effects ultimately induced cuproptosis and enhanced the response of radioresistant NSCLC cells to IR. Our findings highlight the potential of combining cuproptosis targeting with nanotechnology to enhance the efficacy of radiotherapy, presenting a promising strategy to address radioresistance in clinical contexts.

Idiopathic pulmonary fibrosis (IPF) is a fatal and progressive lung disorder. Its pathological process involves persistent epithelial damage, ongoing inflammation, and dysregulated tissue repair. Currently, there are no effective treatment methods to improve patient survival. However, post-translational modifications (PTMs) have gradually garnered widespread attention. They are the processes by which various chemical groups are added to or removed from proteins’ amino acid side chains or the N- or C-terminal ends of the polypeptide chain following synthesis. Additionally, they can regulate the energy supply of cells, regulate the cell cycle, and affect important signaling pathways such as TGF-β. This review systematically summarizes different categories of PTMs, organizes the PTMs involved in various injury stages of IPF, outlines the roles of different cells throughout the process, and analyzes future clinical diagnosis and treatment strategies as well as intervention targets for IPF, providing guiding significance for the systematic intervention of IPF in the future.

Radiation therapy (RT) is one of the core therapies for current cancer management. However, the emergence of radioresistance has become a major cause of radiotherapy failure and disease progression. Therefore, overcoming radioresistance to achieve highly effective treatment for refractory tumors is significant yet challenging. Here, pH‐responsive DSPE‐PEoz modified hollow Bi₂Se₃‐RSL3/diABZi (DP‐HBN/RA) nanomedicine is designed as a radiation sensitizer for efficient treatment of triple‐negative breast cancer by simultaneously amplifying ferroptosis and immune system activation. DP‐HBN/RA can efficiently concentrate X‐ray radiation energy inside the tumor, thereby promoting precise ionizing radiation exposure in tumor cells to produce large amounts of reactive oxygen species (ROS), leading to lipid peroxidation‐induced ferroptosis. Meanwhile, ferroptotic cell death is intensified through the inactivation of GPX4 by RSL3 released from DP‐HBN/RA to acidic conditions in the tumor microenvironment. Additionally, DP‐HBN/RA enhances RT efficacy to exacerbate unrepairable DNA damage and release DNA fragments that activate the cGAS‐STING signal pathway, evoking a systematic immune response. Ingeniously, the released diABZi reinforces cGAS‐STING activation to boost the immunology antitumor effect. This work links the induction of ferroptosis and the initiation of systematic immune response to achieve highly effective tumor suppression, which opens up new avenues for future treatments of refractory tumors.

Liver cancer has high incidence and mortality rates and its treatment generally requires the use of a combination treatment strategy. Therefore, the early detection and diagnosis of liver cancer is crucial to achieving the best treatment effect. In addition, it is imperative to explore multimodal combination therapy for liver cancer treatment and the synergistic effect of two liver cancer treatment drugs while preventing drug resistance and drug side effects to maximize the achievable therapeutic effect. Gold nanoparticles are used widely in applications related to optical imaging, CT imaging, MRI imaging, biomarkers, targeted drug therapy, etc., and serve as an advanced platform for integrated application in the nano-diagnosis and treatment of diseases. Dual-drug-delivery nano-diagnostic and therapeutic agents have drawn great interest in current times. Therefore, the present report aims to review the effectiveness of dual-drug-delivery nano-diagnostic and therapeutic agents in the field of anti-tumor therapy from the particular perspective of liver cancer diagnosis and treatment.

Nanotechnology, an emerging and promising therapeutic tool, may improve the effectiveness of phototherapy (PT) in antitumor therapy because of the development of nanomaterials (NMs) with light-absorbing properties. The tumor-targeted PTs, such as photothermal therapy (PTT) and photodynamic therapy (PDT), transform light energy into heat and produce reactive oxygen species (ROS) that accumulate at the tumor site. The increase in ROS levels induces oxidative stress (OS) during carcinogenesis and disease development. Because of the localized surface plasmon resonance (LSPR) feature of copper (Cu), a vital trace element in the human body, Cu-based NMs can exhibit good near-infrared (NIR) absorption and excellent photothermal properties. In the tumor microenvironment (TME), Cu²⁺ combines with H₂O₂ to produce O₂ that is reduced to Cu¹⁺ by glutathione (GSH), causing a Fenton-like reaction that reduces tumor hypoxia and simultaneously generates ROS to eliminate tumor cells in conjunction with PTT/PDT. Compared with other therapeutic modalities, PTT/PDT can precisely target tumor location to kill tumor cells. Moreover, multiple treatment modalities can be combined with PTT/PDT to treat a tumor using Cu-based NMs. Herein, we reviewed and briefly summarized the mechanisms of actions of tumor-targeted PTT/PDT and the role of Cu, generated from Cu-based NMs, in PTs. Furthermore, we described the Cu-based NMs used in PTT/PDT applications.

Copper serves as a vital microelement which is widely present in the biosystem, functioning as multi-enzyme active site, including oxidative stress, lipid oxidation and energy metabolism, where oxidation and reduction characteristics are both beneficial and lethal to cells. Since tumor tissue has a higher demand for copper and is more susceptible to copper homeostasis, copper may modulate cancer cell survival through reactive oxygen species (ROS) excessive accumulation, proteasome inhibition and anti-angiogenesis. Therefore, intracellular copper has attracted great interest that multifunctional copper-based nanomaterials can be exploited in cancer diagnostics and antitumor therapy. Therefore, this review explains the potential mechanisms of copper-associated cell death and investigates the effectiveness of multifunctional copper-based biomaterials in the field of antitumor therapy.