Unlocking the Potential of Disulfidptosis: Nanotechnology‐Driven Strategies for Advanced Cancer Therapy DOI
Wenyao Zhen, Tianzhi Zhao, Xiaoyuan Chen

et al.

Small, Journal Year: 2025, Volume and Issue: unknown

Published: April 24, 2025

Abstract Tumor tissues exhibit elevated oxidative stress, with the cystine‐glutamate transporter x CT solute carrier family 7 member 11 ( CT/SLC7A11) protecting cancer cells from damage by facilitating cystine uptake for glutathione synthesis. Disulfidptosis, a newly identified form of programmed cell death (PCD), occurs in high CT/SLC7A11 expression under glucose‐deprived conditions. Distinct other PCD pathways, disulfidptosis is characterized aberrant disulfide bond formation and cellular dysfunction, ultimately resulting death. This novel mechanism offers remarkable therapeutic potential targeting inherent stress vulnerabilities rapidly growing cells. Advances nanotechnology enable development nanomaterials capable inducing reactive oxygen species (ROS) generation, disrupting bonds. In addition, they are to deliver agents directly tumors, thereby improving precision minimizing off‐target effects. Moreover, combining ROS‐induced immunogenic can remodel tumor microenvironment enhance anti‐tumor immunity. review explores mechanisms underlying disulfidptosis, its treatment, synergistic role amplifying Selective induction using represents promising strategy achieving more effective, selective, less toxic therapies.

Language: Английский

Nanoscale Mixed-Ligand Metal–Organic Framework for X-ray Stimulated Cancer Therapy DOI
Wenyao Zhen, Ziwan Xu,

Y.Z. Mao

et al.

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 20, 2024

Concurrent localized radiotherapy and systemic chemotherapy are standards of care for many cancers, but these treatment regimens cause severe adverse effects in patients. Herein, we report the design a mixed-ligand nanoscale metal–organic framework (nMOF) with ability to simultaneously enhance radiotherapeutic trigger release potent chemotherapeutic under X-ray irradiation. We synthesized new functional quaterphenyl dicarboxylate ligand conjugated SN38 (H2QP-SN) via hydroxyl radical-responsive covalent linkage. Because similar length QP-SN bis(p-benzoato)porphyrin (DBP) ligands, was incorporated into Hf-DBP nMOF afford novel multifunctional Hf-DBP-QP-SN good biocompatibility. not only enhances radiation damage tumors unique radiotherapy-radiodynamic therapy (RT-RDT) process also increases ·OH generation from radiolysis electron-dense Hf12 secondary building units (SBUs) chemotherapy. Elevated levels hydrogen peroxide tumor microenvironment further stimulate by enhancing With low doses irradiation, suppressed growth CT26 colon 4T1 breast 93.5% 95.2%, respectively, without any sign general toxicity. Our study highlights potential using ionizing radiation-mediated chemistry on-demand activation nanotherapeutics synergistic causing effects.

Language: Английский

Citations

4
Nitric Oxide‐Releasing Nanoscale Metal‐Organic Layer Overcomes Hypoxia and Reactive Oxygen Species Diffusion Barriers to Enhance Cancer Radiotherapy DOI Creative Commons
Yuxuan Xiong, Jinhong Li, Xiaomin Jiang

et al.

Advanced Science, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Abstract Hafnium (Hf)‐based nanoscale metal‐organic layers (MOLs) enhance radiotherapeutic effects of tissue‐penetrating X‐rays via a unique radiotherapy‐radiodynamic therapy (RT‐RDT) process through efficient generation hydroxy radical (RT) and singlet oxygen (RDT). However, their efficacy is limited by hypoxia in deep‐seated tumors short half‐lives reactive species (ROS). Herein the conjugation nitric oxide (NO) donor, S‐nitroso‐N‐acetyl‐DL‐penicillamine (SNAP), to Hf 12 secondary building units (SBUs) Hf‐5,5′‐di‐p‐benzoatoporphyrin MOL reported afford SNAP/MOL for enhanced cancer radiotherapy. Under X‐ray irradiation, efficiently generates superoxide anion (O 2 −. ) releases spatio‐temporally synchronized fashion. The released NO rapidly reacts with O form long‐lived highly cytotoxic peroxynitrite which diffuses freely cell nucleus causes DNA double‐strand breaks. Meanwhile, sustained release from tumor microenvironment relieves reduce radioresistance cells. Consequently, plus low‐dose irradiation inhibits growth reduces metastasis colorectal triple‐negative breast models.

Language: Английский

Citations

0
Synchronously Evoking Disulfidptosis and Ferroptosis via Systematical Glucose Deprivation Targeting SLC7A11/GSH/GPX4 Antioxidant Axis DOI

Mengsi Zhang,

Hao Zheng,

Xuanqi Zhu

et al.

ACS Nano, Journal Year: 2025, Volume and Issue: unknown

Published: April 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.

Language: Английский

Citations

0
Transforming Malignant Tumors into Vulnerable Phenotypes via Nanoscale Coordination Polymer Mediated Cell Senescence and Photodynamic Therapy DOI
Wenyao Zhen, Xiaomin Jiang, E. Li

et al.

Biomaterials, Journal Year: 2025, Volume and Issue: unknown, P. 123355 - 123355

Published: April 1, 2025

Language: Английский

Citations

0
Unlocking the Potential of Disulfidptosis: Nanotechnology‐Driven Strategies for Advanced Cancer Therapy DOI
Wenyao Zhen, Tianzhi Zhao, Xiaoyuan Chen

et al.

Small, Journal Year: 2025, Volume and Issue: unknown

Published: April 24, 2025

Abstract Tumor tissues exhibit elevated oxidative stress, with the cystine‐glutamate transporter x CT solute carrier family 7 member 11 ( CT/SLC7A11) protecting cancer cells from damage by facilitating cystine uptake for glutathione synthesis. Disulfidptosis, a newly identified form of programmed cell death (PCD), occurs in high CT/SLC7A11 expression under glucose‐deprived conditions. Distinct other PCD pathways, disulfidptosis is characterized aberrant disulfide bond formation and cellular dysfunction, ultimately resulting death. This novel mechanism offers remarkable therapeutic potential targeting inherent stress vulnerabilities rapidly growing cells. Advances nanotechnology enable development nanomaterials capable inducing reactive oxygen species (ROS) generation, disrupting bonds. In addition, they are to deliver agents directly tumors, thereby improving precision minimizing off‐target effects. Moreover, combining ROS‐induced immunogenic can remodel tumor microenvironment enhance anti‐tumor immunity. review explores mechanisms underlying disulfidptosis, its treatment, synergistic role amplifying Selective induction using represents promising strategy achieving more effective, selective, less toxic therapies.

Language: Английский

Citations

0