Durable glioblastoma multiforme (GBM) management requires long‐term chemotherapy after surgery to eliminate remaining cancerous tissues. Among chemotherapeutics, temozolomide is considered as the first‐line drug for GBM therapy, but the treatment outcome is not satisfactory. Notably, regorafenib, an oral multi‐kinase inhibitor, has been reported to exert a markedly superior effect on GBM suppression compared with temozolomide. However, poor site‐specific delivery and bioavailability significantly restrict the efficient permeability of regorafenib to brain lesions and compromise its treatment efficacy. Therefore, human H‐ferritin (HFn), regorafenib, and Cu2+ are rationally designed as a brain‐targeted nanoplatform (HFn‐Cu‐REGO NPs), fulfilling the task of site‐specific delivery and manipulating autophagy and cuproptosis against GBM. Herein, HFn affords a preferential accumulation capacity to GBM due to transferrin receptor 1 (TfR1)‐mediated active targeting and pH‐responsive delivery behavior. Moreover, regorafenib can inhibit autophagosome‐lysosome fusion, resulting in lethal autophagy arrest in GBM cells. Furthermore, Cu2+ not only facilitates the encapsulation of regorafenib to HFn through coordination interaction but also disturbs copper homeostasis for triggering cuproptosis, resulting in a synergistical effect with regorafenib‐mediated lethal autophagy arrest against GBM. Therefore, this work may broaden the clinical application scope of Cu2+ and regorafenib in GBM treatment via modulating autophagy and cuproptosis.

Inflammatory bowel disease (IBD) is a long-term, progressive, and recurrent intestinal inflammatory disorder. The pathogenic mechanisms of IBD are multifaceted and associated with oxidative stress, unbalanced gut microbiota, and aberrant immune response. Indeed, oxidative stress can affect the progression and development of IBD by regulating the homeostasis of the gut microbiota and immune response. Therefore, redox-targeted therapy is a promising treatment option for IBD. Recent evidence has verified that Chinese herbal medicine (CHM)-derived polyphenols, natural antioxidants, are able to maintain redox equilibrium in the intestinal tract to prevent abnormal gut microbiota and radical inflammatory responses. Here, we provide a comprehensive perspective for implementing natural antioxidants as potential IBD candidate medications. In addition, we demonstrate novel technologies and stratagems for promoting the antioxidative properties of CHM-derived polyphenols, including novel delivery systems, chemical modifications, and combination strategies.

Polyphenols and their derivates, a kind of natural product distributed in herb plants, vegetables, and fruits, are the most abundant antioxidants in the human diet and have been found to display cancer-preventative effects in several epidemiological studies. The scientific community has also validated the anti-cancer bioactivities and low toxicities of polyphenolic compounds, including flavones, tannins, phenolic acids, and anthocyanins, through in vitro and in vivo studies. However, the low stability, weak targeting ability, poor solubility, and low bioavailability of pure polyphenolic agents have significantly impaired their treatment efficacy. Nowadays, nano-based technology has been applied to surmount these restrictions and maximize the treatment efficacy of polyphenols. In this review, we summarize the advantages and related mechanisms of polyphenols in cancer treatment. Moreover, aiming at the poor solubility and low bioavailability of pure polyphenols in vivo, the advantages of nano-based delivery systems and recent research developments are highlighted. Herein, particular emphasis is mainly placed on the most widely used nanomaterials in the delivery of natural products, including liposomes, micelles, and nanogels. Finally, we present an overview and the challenges of future implementations of nano-based delivery systems of polyphenolic compounds in the cancer therapeutic field.

Peroxiredoxin 6 (PRDX6) is widely distributed in several organs, especially the lungs. The role of PRDX6 in oxidative stress is controversial and even contradictory, as indicated by research conducted over the past 20 years. PRDX6 has anti-oxidant or pro-oxidant effects on oxidative stress in different diseases. It can even exhibit both anti-oxidant and pro-oxidant effects in the same disease. These findings are attributed to the fact that PRDX6 is a multifunctional enzyme. The peroxidase and phospholipase A2 activity of PRDX6 is closely related to its anti-oxidant and pro-oxidant effects, which leads to the conflicting regulatory effects of PRDX6 on oxidative stress in respiratory diseases. Moreover, PRDX6 interacts with multiple redox signaling pathways to interfere with cell proliferation and apoptosis. PRDX6 has become a new target in respiratory disease research due to its important regulatory role in oxidative stress. In this paper, the role of PRDX6 in oxidative stress in respiratory diseases and the research progress in targeting PRDX6 are reviewed.