Combating cancer immunotherapy resistance: a nano‐medicine perspective

Cancer Communications, Год журнала: 2025, Номер unknown

Опубликована: Апрель 10, 2025

Abstract Cancer immunotherapy offers renewed hope for treating this disease. However, cancer cells possess inherent mechanisms that enable them to circumvent each stage of the immune cycle, thereby evading anti‐cancer immunity and leading resistance. Various functionalized nanoparticles (NPs), modified with cationic lipids, pH‐sensitive compounds, or photosensitizers, exhibit unique physicochemical properties facilitate targeted delivery therapeutic agents tumor microenvironment (TME). These NPs are engineered modify activity. The crucial signal transduction pathways by which counteract resistance outlined, including enhancing antigen presentation, boosting activation infiltration tumor‐specific cells, inducing immunogenic cell death, counteracting immunosuppressive conditions in TME. Additionally, review summarizes current clinical trials involving NP‐based immunotherapy. Ultimately, it highlights potential nanotechnology advance

Язык: Английский

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Establishment of a prognostic signature and immune infiltration characteristics for uterine corpus endometrial carcinoma based on a disulfidptosis/ferroptosis-associated signature

Frontiers in Immunology, Год журнала: 2025, Номер 16

Опубликована: Янв. 27, 2025

Background Disulfidptosis and ferroptosis are two different programmed cell death pathways, their potential therapeutic targets have important clinical prospects. Although there is an association between the two, role of genes associated with these forms in development endometrial cancer remains unclear. Methods In this study, RNA sequencing (RNA-seq) data were obtained from public databases, comprehensive analysis methods, including difference analysis, univariate Cox regression, Least Absolute Shrinkage Selection Operator (LASSO) used to construct a disulfidptosis/ferroptosis-related (DFRGs) prognostic signature. To further explore new feature, pathway functional analyses performed, differences gene mutation frequency level immune infiltration high- low-risk groups studied. Finally, we validated expression profile samples. Results We identified five optimal DFRGs that differentially expressed prognosis uterine corpus carcinoma (UCEC). These include CDKN2A, FZD7, LCN2, ACTN4, MYH10. Based on DFRGs, constructed robust model significantly lower overall survival high-risk group than group, tumor burden invasion risk groups. The key genes, ACTN4 was verified by immunohistochemistry RT-qPCR. Conclusion This study established characteristics assessment disulfidptosis provides insights guide patient management personalized treatment.

Язык: Английский

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Targeting novel regulated cell death: disulfidptosis in cancer immunotherapy with immune checkpoint inhibitors

Biomarker Research, Год журнала: 2025, Номер 13(1)

Опубликована: Фев. 26, 2025

Abstract The battle against cancer has evolved over centuries, from the early stages of surgical resection to contemporary treatments including chemotherapy, radiation, targeted therapies, and immunotherapies. Despite significant advances in treatment recent decades, these therapies remain limited by various challenges. Immune checkpoint inhibitors (ICIs), a cornerstone tumor immunotherapy, have emerged as one most promising advancements treatment. Although ICIs, such CTLA-4 PD-1/PD-L1 inhibitors, demonstrated clinical efficacy, their therapeutic impact remains suboptimal due patient-specific variability immune resistance. Cell death is fundamental process for maintaining tissue homeostasis function. Recent research highlights that combination induced regulatory cell (RCD) ICIs can substantially enhance anti-tumor responses across multiple types. In cells exhibiting high levels recombinant solute carrier family 7 member 11 (SLC7A11) protein, glucose deprivation triggers programmed (PCD) pathway characterized disulfide bond formation REDOX (reduction-oxidation) reactions, termed “disulfidptosis.” Studies suggest disulfidptosis plays critical role efficacy SLC7A11 cancers. Therefore, investigate potential synergy between this study will explore mechanisms both processes progression, with goal enhancing response targeting intracellular pathway.

Язык: Английский

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Exploiting metabolic vulnerabilities through synergistic ferroptosis and disulfidptosis for breast cancer therapy

Journal of Advanced Research, Год журнала: 2025, Номер unknown

Опубликована: Март 1, 2025

Ferroptosis represents a promising therapeutic approach for breast cancer treatment. However, cells can develop resistance through the SLC7A11-GSH-GPX4 axis, wherein increased SLC7A11 expression enhances cystine uptake, replenishes GSH, and reactivates GPX4. Notably, with high become vulnerable to disulfidptosis under glucose-deprived conditions. We aimed dual-mode strategy that simultaneously induces ferroptosis by targeting both lipid peroxidation glucose metabolism in cells. Fe-Cu-SS metal-organic frameworks (MOFs) loaded BAY876 (FCSP@876 MOFs) were synthesized enhance trigger The MOFs characterized using transmission electron microscopy (TEM), Fourier-transform infrared (FTIR) spectroscopy, X-ray photoelectron spectroscopy (XPS), UV-Vis spectroscopy. In vitro experiments demonstrated FCSP@876 reactive oxygen species (ROS) levels while depleting NADPH. Western blotting actin filament staining confirmed underlying mechanisms. vivo xenograft BALB/c mice assessed synergistic effects of induction. During induction, exhibited an adaptive upregulation expression. effectively counteracted this mechanism inducing restricting uptake BAY876, leading NADPH depletion subsequent disulfidptosis. Both enhanced efficacy compared single-mode treatments. This study successfully developed novel combines MOFs, offering overcoming therapy.

Язык: Английский

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Synchronously Evoking Disulfidptosis and Ferroptosis via Systematical Glucose Deprivation Targeting SLC7A11/GSH/GPX4 Antioxidant Axis

ACS Nano, Год журнала: 2025, Номер unknown

Опубликована: Апрель 3, 2025

Disulfidptosis and ferroptosis are recently identified programmed cell deaths for tumor therapy, both of which highly depend on the intracellular cystine/cysteine transformation cystine transporter solute carrier family 7 member 11/glutathione/glutathione peroxidase 4 (SLC7A11/GSH/GPX4) antioxidant axis. However, disulfidptosis usually asynchronous due to opposite effect transport them. Herein, systematic glucose deprivation, by inhibiting upstream uptake promoting downstream consumption, is proposed synchronously evoke ferroptosis. As an example, Au nanodots Fe-apigenin (Ap) complexes coloaded FeOOH nanoshuttles (FeOOH@Fe-Ap@Au NSs) employed regulate SLC7A11/GSH/GPX4 axis performing disulfidptosis- ferroptosis-mediated therapy synchronously. In this scenario, exhibit oxidase-like activity when consuming massive glucose. Meanwhile, Ap can inhibit downregulating 1, depriving fundamentally. The systematical deprivation limits supplement NADPH suppresses axis, thus solving contradiction addition, efficient delivery exogenous iron ions FeOOH@Fe-Ap@Au NSs self-supplied H2O2 through nanodots-catalytic oxidation facilitate Fenton reaction therewith help amplify a result synchronous occurrence ferroptosis, good efficacy in ovarian cancer therapeutic model.

Язык: Английский

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Total antioxidant capacity assessment and accurate quantification of ascorbic acid and glutathione utilizing the enhanced multi-mimetic of Cu-CeO₂ NPs decorated PCN-224

Sensors and Actuators B Chemical, Год журнала: 2025, Номер unknown, С. 137709 - 137709

Опубликована: Апрель 1, 2025

Язык: Английский

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Redox-driven hybrid nanoenzyme dynamically activating ferroptosis and disulfidptosis for hepatocellular carcinoma theranostics

Journal of Colloid and Interface Science, Год журнала: 2025, Номер 693, С. 137611 - 137611

Опубликована: Апрель 15, 2025

Язык: Английский

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