Bioinspired Bimetallic Ions Functionalized MOF SAzyme Nanocomposites for Synergistic Ferroptosis/Cuproptosis-Enhanced Immune Checkpoint Therapy DOI Creative Commons

Linjiao Yang,

Mengmeng Pan,

Haofan Hu

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Авг. 16, 2024

Abstract Immune checkpoint blockade (ICB) generates sustained responses in immunogenic cancers, but its effectiveness is limited tumors lacking immune activity. Here, we construct a bioinspired bimetallic ions functionalized nanoscale metal-organic framework (NMOF) single-atom nanozyme (SAzyme) loaded with doxorubicin (Dox) (NMOF-Fe/Cu-Dox nanocomposite) to effectively trigger anti-tumor while addressing the immunosuppressive tumor microenvironment (TME). The NMOF-Fe/Cu-Dox nanocomposite has been demonstrated efficiently reverse TME by generating reactive oxygen species and oxidizing glutathione. Camouflaging nanocomposites cancer cell membrane (NMOF-Fe/Cu-Dox@M) enables navigation region through homologous targeting. highly efficient uptaken cells selectively induced synergistic ferroptosis cuproptosis these cells. Furthermore, vitro vivo experiments demonstrate that can polarize tumor-associated macrophages (TAMs) towards anti-tumoral M1 phenotype significantly diminish pro-tumoral M2 phenotype. We find NMOF-Fe/Cu-Dox@M could induce of macrophages, no effect macrophages. In addition, significant increase infiltrating CD8 + T cells, remarkable decrease CD4 regulatory were observed. These findings suggested modulate TME, enhance tumoricidal immunity elevate therapeutic efficiency ICB. Moreover, combination αPD-1 eradicated hepatocellular carcinoma , outperforming use either or alone. summary, our study presents strategy leverages coordinated ICB, underscoring promise combined chemoimmunotherapy.

Язык: Английский

A strategy of “adding fuel to the flames” enables a self-accelerating cycle of ferroptosis-cuproptosis for potent antitumor therapy DOI
Lin Huang,

Jiaoyang Zhu,

Guochao Wu

и другие.

Biomaterials, Год журнала: 2024, Номер 311, С. 122701 - 122701

Опубликована: Июль 6, 2024

Язык: Английский

Процитировано

20
Targeting cuproptosis for cancer therapy: mechanistic insights and clinical perspectives DOI Creative Commons
Chenliang Zhang, Tingting Huang, Liping Li

и другие.

Journal of Hematology & Oncology, Год журнала: 2024, Номер 17(1)

Опубликована: Авг. 16, 2024

Cuproptosis is a newly identified form of cell death induced by excessive copper (Cu) accumulation within cells. Mechanistically, cuproptosis results from Cu-induced aggregation dihydrolipoamide S-acetyltransferase, correlated with the mitochondrial tricarboxylic acid cycle and loss iron–sulfur cluster proteins, ultimately resulting in proteotoxic stress triggering death. Recently, has garnered significant interest tumor research due to its potential as crucial therapeutic strategy against cancer. In this review, we summarized cellular molecular mechanisms relationship other types Additionally, reviewed current drugs or strategies available induce cells, including Cu ionophores, small compounds, nanomedicine. Furthermore, targeted metabolism specific regulatory genes cancer therapy enhance sensitivity cuproptosis. Finally, discussed feasibility targeting overcome chemotherapy immunotherapy resistance suggested future directions. This study that could open new avenues for developing therapy.

Язык: Английский

Процитировано

11
Redox-manipulating nanocarriers for anticancer drug delivery: a systematic review DOI Creative Commons
Xuan Meng,

Yongli Shen,

Huanyu Zhao

и другие.

Journal of Nanobiotechnology, Год журнала: 2024, Номер 22(1)

Опубликована: Сен. 28, 2024

Язык: Английский

Процитировано

11
Engineered‐Doping Strategy for Self‐Sufficient Reactive Oxygen Species Blossom to Amplify Ferroptosis/Cuproptosis Sensibilization in Hepatocellular Carcinoma Treatment DOI
Jiahe Hu, Jiuxin Zhu, Kuan Wang

и другие.

Advanced Functional Materials, Год журнала: 2024, Номер 34(46)

Опубликована: Июнь 11, 2024

Abstract Ferroptosis and cuproptosis are emerging modes of programmed cell death have been increasingly used to eliminate tumor cells. However, converting ferroptosis/cuproptosis into effective treatments is challenging because the inherent antioxidant plasma membrane repair systems inefficient copper ion delivery. Herein, an engineered doping method developed encapsulate ZnO 2 with Cu 2+ ‐doped ZIF‐8 modify surface by transferrin (Tf). In resulting @Cu/ZIF‐8‐Tf nanosystem, Tf specifically binds receptors for targeting aggregation. microenvironment, /Fe 3+ released from nanosystem reacted glutathione (GSH) produce + . Excessive accumulation interfered tricarboxylic acid cycle induced coproptosis. Furthermore, additional Fe caused iron overload enhanced ferroptosis. supplied hydrogen peroxide mediate overproduction reactive oxygen species (ROS). Moreover, depletion GSH deactivated peroxidase 4 (GPX4) inhibited system X c − ‐GSH‐GPX4 pathway, amplified ROS triggered lipid peroxidation reprogrammed metabolism, causing malfunctioning both systems. summary, pathways activated at multiple levels in which ensures its outstanding antitumor effect.

Язык: Английский

Процитировано

8
Copper-Based Biomaterials for Anti-Tumor Therapy: Recent Advances and Perspectives DOI
Shufang Zhang, Shuping Peng

Acta Biomaterialia, Год журнала: 2025, Номер unknown

Опубликована: Янв. 1, 2025

Язык: Английский

Процитировано

1
Dual‐Release Free Iron and Breakdown of Ferroptosis Defenses to Achieve Ferroptosis Cascade Storms for Potent Antitumor Therapy DOI Open Access

Wenting Xu,

Yuzhen Yang, Lijuan Liu

и другие.

Advanced Functional Materials, Год журнала: 2025, Номер unknown

Опубликована: Янв. 19, 2025

Abstract Ferroptosis is a newly identified type of regulated cell death characterized by iron‐dependent lipid peroxidation. Among the main ferroptosis‐suppressing systems, dihydroorotate dehydrogenase (DHODH)‐ ubiquinone axis closely related to mitochondria and energy metabolism, implying that protects cells from oxidative stress damage via maintenance redox homeostasis. However, ferroptosis initiation requires suitable environment breakthrough in homeostatic limitations systems. Hence, nanoparticles are rationally engineered achieve efficient induction releasing dual‐release free iron disrupting Atovaquone (ATO)‐loaded hollow mesoporous etching zeolitic imidazolate framework‐67 double‐coated oxide/calcium phosphate (Fe 3 O 4 /CaP) conjugated with polyethylene glycol. The external Fe /CaP structure enhances efficiency multiple reactive oxygen species (ROS) generation promoting stress. Still, it achieves increase content unstable pools for igniting ROS storm peroxidation spark. release ATO not only affects metabolism mitochondrial respiratory chain binding complex III but also downregulates DHODH restrict ubiquinol system disrupt Therefore, design this composite nanomedicine provides an approach inducing theoretical basis clinical anti‐tumor trials.

Язык: Английский

Процитировано

1
Advances in cuproptosis harnessing copper-based nanomaterials for cancer therapy DOI
Yuanying Yang, Chen Dong, Xuehua Ma

и другие.

Journal of Materials Chemistry B, Год журнала: 2025, Номер unknown

Опубликована: Янв. 1, 2025

This review discusses the recent developments in copper-based nanomaterials that utilize copper-induced cell death, categorized by materials systems, while highlighting limitations of current cuproptosis related nanomaterials.

Язык: Английский

Процитировано

1
Nanoparticle‐Mediated Cuproptosis and Photodynamic Synergistic Strategy: A Novel Horizon for Cancer Therapy DOI Creative Commons
Junrui Zhang,

Anren Zhang,

Yibing Guo

и другие.

Cancer Medicine, Год журнала: 2025, Номер 14(3)

Опубликована: Янв. 27, 2025

Photodynamic therapy (PDT) is a noninvasive cancer treatment that works by using light to stimulate the production of excessive cytotoxic reactive oxygen species (ROS), which effectively eliminates tumor cells. However, therapeutic effects PDT are often limited hypoxia, prevents effective cell elimination. The (O2) consumption during can further exacerbate leading post-treatment adverse events. This review aims explore potential cuproptosis, recently discovered copper-dependent form programmed death, enhance anticancer PDT. Cuproptosis highly dependent on mitochondrial respiration, specifically tricarboxylic acid (TCA) cycle, and increase O2 ROS levels or decrease glutathione (GSH) levels, thereby improving outcomes. discusses latest research advancements in field, detailing mechanisms regulate cuproptosis It also explores how nanoparticle (NP)-based strategies be used exploit synergistic between article examines prospects activity guided nanodelivery systems, could overcome challenges associated with hypoxia treatment. combination PDT, facilitated NP-based delivery presents promising approach effectiveness therapy. concludes discussing future directions for this therapy, highlighting need investigation into optimization improve outcomes

Язык: Английский

Процитировано

1
HPB@LA@PDA nanoplatform ameliorates osteoarthritis by scavenging reactive oxygen species and remodelling the inflammatory microenvironment: An in vitro and in vivo study DOI

Dongze Ren,

Mingjie Liu,

Min Cao

и другие.

Chemical Engineering Journal, Год журнала: 2025, Номер unknown, С. 160592 - 160592

Опубликована: Фев. 1, 2025

Язык: Английский

Процитировано

1
Apoptosis‐Sensitizing Tumor Nanomedicine by Regulating Pyroptosis‐Associated Inflammatory Cell Death DOI

Fangxue Du,

Hongxin Zhao,

Yangmeihui Song

и другие.

Advanced Functional Materials, Год журнала: 2024, Номер 34(44)

Опубликована: Май 25, 2024

Abstract The vigorous development of cancer nanomedicine has revolutionized traditional oncology medicine, but it is also limited by the continuous mutation cunning cells, leading to apoptosis insensitivity and therapeutic disappointment. Inflammatory‐regulated cell death (RCD), especially pyroptosis‐related death, demonstrates huge potential for sensitization due its unique biochemical characteristics. aim this research present a thorough synopsis current knowledge on pyroptosis‐associated inflammatory including pyroptosis, cuproptosis, PANoptosis, synergistic function in nano therapy. Paradigm studies death‐mediated apoptosis‐sensitizing tumor nanotherapeutics are introduced detail, coordination mechanisms based nanomaterials discussed. In addition, multi‐angle analysis future prospects pyroptosis‐sensitized various emphasized further expand application scope RCD. It believed that emerging auxiliary treatments RCD will greatly promote progress nanomedicine.

Язык: Английский

Процитировано

7