Redox homeostasis refers to the dynamic equilibrium between oxidant and reducing agent in the body which plays a crucial role in maintaining normal physiological activities of the body. The imbalance of redox homeostasis can lead to the development of various human diseases. Lysosomes regulate the degradation of cellular proteins and play an important role in influencing cell function and fate, and lysosomal dysfunction is closely associated with the development of various diseases. In addition, several studies have shown that redox homeostasis plays a direct or indirect role in regulating lysosomes. Therefore, this paper systematically reviews the role and mechanisms of redox homeostasis in the regulation of lysosomal function. Therapeutic strategies based on the regulation of redox exerted to disrupt or restore lysosomal function are further discussed. Uncovering the role of redox in the regulation of lysosomes helps to point new directions for the treatment of many human diseases.

Glucose transporter 1 (GLUT1), a central orchestrator of tumor metabolic reprogramming, sustains malignant progression by enforcing glycolytic dependency and conferring therapeutic resistance. While conventional GLUT1-targeted small-molecule inhibitors demonstrate preclinical efficacy through glucose transport blockade and chemo-radiosensitization, their clinical translation is impeded by intrinsic limitations. Emerging nanomedicine paradigms have redefined GLUT1-targeted interventions through multifunctional platforms that synergistically unify precision therapeutics, imaging guidance, and immunometabolic modulation. Meanwhile, advanced formulations further exploit GLUT1-mediated endocytosis to achieve blood-brain barrier penetration, thus potentially addressing key challenges in the treatment of CNS malignancies. Notably, combinatorial nanoarchitectures simultaneously disrupt metabolic pathways and reprogram immunosuppressive niches via dual-targeting strategies, thereby counteracting tumor adaptation mechanisms. These innovations transcend conventional therapeutic boundaries by establishing metabolic-immune interplay regulation and barrier-defying delivery systems. This review systematically analyses the evolving landscape of GLUT1-targeted nanomedicine, evaluating both traditional molecular inhibitors and next-generation nanoplatforms that harness GLUT1 through diverse modalities. By dissecting molecular mechanisms and translational applications, we elucidate the diagnostic and therapeutic value of GLUT1-targeted nano-strategies in precision oncology while outlining future directions for clinical implementation.

Inducing immunogenic cell death (ICD) can tackle the issue of low immune response levels in tumor immunotherapy. Photodynamic therapy (PDT) uses photosensitizers to generate reactive oxygen species that kill tumor cells, while photothermal therapy (PTT) directly uses heat from photothermal converters to destroy tumor cells. However, these single treatments have their limitations. The development of optical therapy nanodelivery systems, along with the combination of PTT/PDT with chemotherapy and immunotherapy, offers new strategies for tumor immunotherapy. This article explores the application of PDT and PTT mediated by nanodelivery systems in promoting immunogenic cell death in tumor cells. This article explores nano-delivery systems that precisely release photosensitizers to boost efficacy and reduce toxicity. It also discusses their potential for combination therapy through co-delivery, utilizing multimodal strategies to enhance both phototherapy and chemotherapy, thus improving anticancer effectiveness.

Background: Circular RNAs (circRNAs) have been proven to function as pivotal regulators in cancer occurrence and progression. However, the function of circ_0006404 (circRNA Forkhead box O3 (circFOXO3)in prostate cancer (PCa) is poorly understood. Methods: The enrichment of circ_0006404, FOXO3, microRNA-1299 (miR-1299) and cofilin 2 (CFL2) was measured by quantitative real-time polymerase chain reaction (qRT-PCR). The viability, metastasis and proliferation were determined by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, transwell and colony formation assays, respectively. Flow cytometry was used to assess cell cycle progression and apoptosis. Circ_0006404/miRNAs interactions were explored using Circular RNA Interactome database, while TargetScan software was used for seeking the targets of miR-1299. Dual-luciferase reporter assay, RNA-pull down and RNA immunoprecipitation (RIP) assays were conducted to verify the target interaction between miR-1299 and circ_0006404 or CFL2. CFL2 protein level was analyzed by Western blot assay. Animal experiments were performed to test the role of circ_0006404 in PCa tumor growth in vivo. Results: Circ_0006404 level was notably elevated in PCa. Circ_0006404 contributed to the viability, metastasis and proliferation and impaired the apoptosis of PCa cells. Circ_0006404 directly targeted miR-1299, and miR-1299 silencing largely reversed circ_0006404 interference-induced influences in PCa cells. CFL2 directly bound to miR-1299, and miR-1299-induced effects in PCa cells were largely attenuated by CFL2 overexpression. CFL2 was regulated by circ_0006404/miR-1299 axis in PCa cells. Circ_0006404 promoted PCa progression via miR-1299/CFL2 axis in vivo. Conclusion: Circ_0006404 accelerated the survival, motility and proliferation while impeded the apoptosis of PCa cells via miR-1299/CFL2 axis. Circ_0006404 might be a stable potential bio-marker for PCa diagnosis and treatment.

Macromolecular Drugs (including monoclonal antibodies, recombinant proteins, and nucleic acid therapies) have become a cornerstone strategy for intervening in complex pathological mechanisms such as cancer, autoimmune diseases, and genetic disorders due to their high specificity for disease targets and low off-target toxicity. However, compared to traditional small-molecule drugs, the high molecular weight (> 10 kDa) and structural complexity of macromolecular drugs result in extremely low transmembrane permeability. This is particularly challenging in the treatment of central nervous system (CNS) diseases, where the blood-brain barrier (BBB) imposes stringent selectivity, further limiting drug delivery efficiency. This review focuses on the breakthrough strategy of nose-to-brain (NtB) drug delivery. On one hand, the NtB pathway bypasses the BBB, enabling direct CNS drug delivery. On the other hand, nanocarrier technology can synergistically achieve systemic delivery and brain-targeted transport. Based on the latest research advances, this article systematically examines the feasibility of delivering macromolecular drugs via NtB administration. We comprehensively summarize relevant delivery carriers and discuss the potential advantages of intranasal-brain delivery for CNS disease treatment. Notably, while significant progress has been made in this field, further exploration is still needed regarding the mechanisms of NtB delivery and challenges in clinical translation.

Epigenetic dysregulation can significantly trigger the onset and progression of various diseases, epigenetic therapy is a new treatment strategy by changing DNA methylation, histone modification, N6-methyladenosine, chromatin modification and other epigenetic modifications to regulate gene expression levels for therapeutic purposes. However, small-molecule epigenetic drugs face challenges in disease treatment, such as lack of selectivity, limited therapeutic efficacy, and insufficient safety. Nanomedicine delivery systems offer significant advantages in addressing these issues by enhancing drug targeting, improving bioavailability, and reducing nonspecific distribution. This help minimize side effects while increasing both therapeutic effectiveness and safety of epigenetic drugs. In this review, we focus on the mechanism and role of epigenetic regulatory factors in diseases, as well as the challenges faced by small molecule inhibitors in treatment strategies, especially the research advancements in epigenetic drug delivery systems, review and discuss the therapeutic potential and challenges of using nanotechnology to develop epigenetic drug delivery systems.