Advanced Healthcare Materials最新文献_第8页

Glutathione-Responsive Fluorinated Nanogels Enabling Dual-Modal Imaging and Photodynamic Therapy. 谷胱甘肽响应氟化纳米凝胶实现双模成像和光动力治疗。

IF 9.6 2区医学

Advanced Healthcare Materials Pub Date : 2025-10-05 DOI: 10.1002/adhm.202503300

Zixuan Wu, Shengjun Huo, Xiaotong Liang, Kai Wang, Danfeng Peng, Dalin Wu, Zhong Cao

{"title":"Glutathione-Responsive Fluorinated Nanogels Enabling Dual-Modal Imaging and Photodynamic Therapy.","authors":"Zixuan Wu, Shengjun Huo, Xiaotong Liang, Kai Wang, Danfeng Peng, Dalin Wu, Zhong Cao","doi":"10.1002/adhm.202503300","DOIUrl":"https://doi.org/10.1002/adhm.202503300","url":null,"abstract":"19F magnetic resonance imaging (19F MRI) is an emerging non-invasive imaging modality with a high signal-to-noise ratio (SNR) and negligible background interference from biological tissues. However, the hydrophobic nature of fluorine atoms limits both 19F signal intensity and in vivo applicability. Therefore, developing fluorinated MRI contrast agents that combine high fluorine content with good hydrophilicity is essential for advancing in vivo 19F MRI. In this study, a fluorine-containing nanogel (FNG) is synthesized via emulsion polymerization and de-protection using trifluoroethyl methacrylate (TFMA) and tert-butyl acrylate (t-BA). The FNG is then loaded with the near-infrared photosensitizer IR780 to obtain a multifunctional imaging probe (IFNG) capable of dual-modal 19F MR and fluorescence (FL) imaging-guided photodynamic therapy (PDT). The resulting IFNG exhibited a T2 relaxation time of 46.32 ms, confirming its excellent MRI performance in vitro. In the tumor microenvironment, IFNG undergoes glutathione (GSH)-responsive decrosslinking, which exposes the encapsulated IR780. This process enhances fluorescence signal and promotes reactive oxygen species (ROS) generation under near-infrared light, thereby triggering effective PDT. Overall, these findings demonstrate IFNG as a promising nanoplatform that integrates dual-modal 19F MR/FL imaging with GSH-activated photodynamic therapy, offering great potential for precise tumor localization and image-guided cancer treatment.","PeriodicalId":113,"journal":{"name":"Advanced Healthcare Materials","volume":" ","pages":"e03300"},"PeriodicalIF":9.6,"publicationDate":"2025-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145231226","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

In Vivo Bioorthogonal Radiolabeling of Nanoparticles to Minimize Liver Radiation. 纳米颗粒体内生物正交放射性标记以减少肝脏辐射。

IF 9.6 2区医学

Advanced Healthcare Materials Pub Date : 2025-10-04 DOI: 10.1002/adhm.202503438

Yun Gao, Xiaotong Wang, Can Chen, Lei Chen, Xiaoyi Cao, Mengyao Wu, Yi Zhou, Jianfeng Zeng, Mingyuan Gao

{"title":"In Vivo Bioorthogonal Radiolabeling of Nanoparticles to Minimize Liver Radiation.","authors":"Yun Gao, Xiaotong Wang, Can Chen, Lei Chen, Xiaoyi Cao, Mengyao Wu, Yi Zhou, Jianfeng Zeng, Mingyuan Gao","doi":"10.1002/adhm.202503438","DOIUrl":"https://doi.org/10.1002/adhm.202503438","url":null,"abstract":"Radiolabeled nanoparticles hold great promise in precision medicine due to its versatile applications in disease imaging and therapy. However, its clinical translation is often hindered by excessive accumulation in reticuloendothelial system organs, particularly the liver, which can lead to radiation-induced toxicity. Herein, an in vivo selective radiolabeling strategy is reported that exploits the distinct subcellular fates of nanoparticles in tumors versus liver. A biorthogonal nanosystem composed of trans-cyclooctene (TCO)-functionalized iron oxide nanoparticles (Fe3O4@TCO) and a radiolabeled tetrazine probe (177Lu-DOTA-Tz) is constructed to validate this concept. Owing to the hydrophilic nature, 177Lu-DOTA-Tz cannot penetrate cell membranes, resulting in spatially restricted bioorthogonal labeling in the extracellular space. At tumor sites, Fe3O4@TCO nanoparticles accumulate via the enhanced permeability and retention effect and remain accessible for efficient binding with 177Lu-DOTA-Tz. In contrast, in the liver, nanoparticles are predominantly internalized by liver cells, and its intracellular localization prevents interaction with the probe, thereby minimizing hepatic radiation retention. By harnessing these subcellular distribution differences, the approach achieves selective in vivo radiolabeling and significantly improves the tumor-to-liver radiation ratio. This study provides a biologically informed strategy for designing radiolabeled nanoplatforms with enhanced safety profiles for theranostic applications.","PeriodicalId":113,"journal":{"name":"Advanced Healthcare Materials","volume":" ","pages":"e03438"},"PeriodicalIF":9.6,"publicationDate":"2025-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145224680","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Personalized Alginate Encapsulation: The Role of Autologous Blood Additives in Parathyroid Cell Transplantation. 个性化海藻酸盐包封：自体血液添加剂在甲状旁腺细胞移植中的作用。

IF 9.6 2区医学

Advanced Healthcare Materials Pub Date : 2025-10-04 DOI: 10.1002/adhm.202501483

Özge Karabıyık Acar, Gülnihal Bozdağ, Ahmed Alperen Tuncer, Ezgi Hacıhasanoğlu, Lal Era Aydoğan, Gülçin Delal Nozhatzadeh, Fikrettin Şahin, Erhan Aysan, Gamze Torun Köse

{"title":"Personalized Alginate Encapsulation: The Role of Autologous Blood Additives in Parathyroid Cell Transplantation.","authors":"Özge Karabıyık Acar, Gülnihal Bozdağ, Ahmed Alperen Tuncer, Ezgi Hacıhasanoğlu, Lal Era Aydoğan, Gülçin Delal Nozhatzadeh, Fikrettin Şahin, Erhan Aysan, Gamze Torun Köse","doi":"10.1002/adhm.202501483","DOIUrl":"https://doi.org/10.1002/adhm.202501483","url":null,"abstract":"The only therapeutic intervention for hypoparathyroidism is parathyroid transplantation, but graft rejection is a concern. This study sought to mitigate this problem by utilizing the patient's blood, serum, or plasma in the transplant. To accomplish this objective, blood additives derived from Sprague-Dawley rats are incorporated within alginate, and human parathyroid cells are encapsulated. The prepared microbeads are monitored for mechanical properties, followed by xenotransplantation into rats for the evaluation of cell function and immunological response. Biodegradation data showed that the structural integrity of the microbeads containing blood and plasma is superior to serum, while the durability of plasma-including microbeads is only comparable to that of the alginate-only group. Plasma-including microbeads released the highest levels of parathyroid hormone (PTH), both in vitro and in vivo. This behavior could be attributed to the beneficial impact of plasma on cellular function while regulating immune response. Blood incorporation provoked an elevated immune response while concurrently offering minimal support to the encapsulated cells. A notable elevation in CCL2 (MCP-1) chemokine levels is observed in both blood and alginate-only microbead groups, correlating with CD68 expression. These findings demonstrated that autologous plasma addition may regulate the immune system, thereby diminishing the risk of rejection in cell transplantations.","PeriodicalId":113,"journal":{"name":"Advanced Healthcare Materials","volume":" ","pages":"e01483"},"PeriodicalIF":9.6,"publicationDate":"2025-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145224749","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Harnessing Next-Generation 3D Cancer Models to Elucidate Tumor-Microbiome Crosstalk. 利用新一代3D癌症模型阐明肿瘤-微生物组串扰。

IF 9.6 2区医学

Advanced Healthcare Materials Pub Date : 2025-10-04 DOI: 10.1002/adhm.202503198

Marina Green Buzhor, Giuseppe Longobardi, Or Kandli, Anne Krinsky, Opal Avramoff, Anshika Katyal, Koren Salomon, Adan Miari, Dana Venkert, Tania T Barnatan, América García Alvarado, Shahar Greenberg, Ronit Satchi-Fainaro

{"title":"Harnessing Next-Generation 3D Cancer Models to Elucidate Tumor-Microbiome Crosstalk.","authors":"Marina Green Buzhor, Giuseppe Longobardi, Or Kandli, Anne Krinsky, Opal Avramoff, Anshika Katyal, Koren Salomon, Adan Miari, Dana Venkert, Tania T Barnatan, América García Alvarado, Shahar Greenberg, Ronit Satchi-Fainaro","doi":"10.1002/adhm.202503198","DOIUrl":"https://doi.org/10.1002/adhm.202503198","url":null,"abstract":"The tumor microenvironment (TME) is a complex and dynamic ecosystem increasingly recognized for its interplay with the microbiome. In colorectal, breast, lung, liver, and brain cancers, bacterial communities and their metabolites are shown to influence tumor progression, immune responses, and therapeutic outcomes. To study these interactions in physiologically relevant contexts, advanced 3D in vitro models have emerged, including spheroids, organoids, microfluidic organ-on-a-chip platforms, and 3D-bioprinted constructs. These systems provide spatial organization, mechanical cues, and co-culture capabilities that facilitate investigation of host-microbiome-tumor cross-talk. Incorporation of live bacteria, their metabolites, and immune components into these platforms has yielded new insights into how the microbiome shapes cancer behavior, inflammation, and drug resistance. This review outlines recent advances in 3D model development for studying tumor-microbiome interactions, highlighting organ-specific applications, extracellular matrix-mimicking hydrogels, and biofabrication strategies. It also addresses key challenges, including maintaining microbiome viability, modeling temporal dynamics, and integrating immune complexity. Overcoming these limitations requires interdisciplinary approaches that merge bioengineering, microbiology, and oncology. Evolving 3D platforms offer powerful tools for microbiome-informed cancer modeling and hold significant promise for advancing therapeutic screening and precision oncology.","PeriodicalId":113,"journal":{"name":"Advanced Healthcare Materials","volume":" ","pages":"e03198"},"PeriodicalIF":9.6,"publicationDate":"2025-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145224688","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

New Biomaterials and Technologies in Growth Plate Regeneration. 生长板再生的新生物材料与技术。

IF 9.6 2区医学

Advanced Healthcare Materials Pub Date : 2025-10-03 DOI: 10.1002/adhm.202501906

Zhiqiang Zhang, Manning Qian, Dahui Wang, Luhan Bao, Wenguo Cui

引用次数: 0

Silencing Myostatin Using In Vivo Self-Assembled siRNA Protects Against Cancer- and Dexamethasone-Induced Muscle Atrophy. 使用体内自组装siRNA沉默肌肉生长抑制素可预防癌症和地塞米松诱导的肌肉萎缩。

IF 9.6 2区医学

Advanced Healthcare Materials Pub Date : 2025-10-03 DOI: 10.1002/adhm.202502186

Xin Yin, Azhar Anwar, Jiehao Chen, Qinghao Sun, Likun Zhou, Jie Tang, Jingwei Guo, Linbo Yan, Yongci Chen, Feng Yin, Chen-Yu Zhang, Zigang Li, Jizheng Ma, Liyuan Sheng, Xi Chen

{"title":"Silencing Myostatin Using In Vivo Self-Assembled siRNA Protects Against Cancer- and Dexamethasone-Induced Muscle Atrophy.","authors":"Xin Yin, Azhar Anwar, Jiehao Chen, Qinghao Sun, Likun Zhou, Jie Tang, Jingwei Guo, Linbo Yan, Yongci Chen, Feng Yin, Chen-Yu Zhang, Zigang Li, Jizheng Ma, Liyuan Sheng, Xi Chen","doi":"10.1002/adhm.202502186","DOIUrl":"https://doi.org/10.1002/adhm.202502186","url":null,"abstract":"Maintaining skeletal muscle mass is crucial for health, as muscle atrophy caused by drugs, cancer, or aging poses serious risks. However, there are few effective pharmacological interventions targeting muscle atrophy, highlighting the need for new therapeutic strategies. In this study, in vivo self-assembled siRNA is designed to silence myostatin (MSTN), a key regulator of muscle growth and atrophy, aiming to prevent muscle atrophy. Using synthetic constructs and the host liver as a scaffold, the assembly of MSTN-siRNA is guided into muscle-specific peptide MSP-tagged small extracellular vesicles (sEVs). These MSP-tagged sEVs selectively deliver MSTN-siRNA to muscle tissue. Treatment significantly reduces MSTN protein levels in skeletal muscle, promotes muscle mass gain in healthy mice, and protectes skeletal muscles from atrophy in cancer- and dexamethasone-induced muscle atrophy models. Notably, the sEV-encapsulated MSTN-siRNA is produced in a nontoxic, nonimmunogenic, and biocompatible manner. This study offers a promising therapeutic approach for muscle atrophy, addressing a key gap in current treatment options and potentially improving outcomes for patients with muscle-wasting conditions.","PeriodicalId":113,"journal":{"name":"Advanced Healthcare Materials","volume":" ","pages":"e02186"},"PeriodicalIF":9.6,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145211157","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Rational Design of Probenecid-Functionalized Silicon Phthalocyanine J-Aggregated Nanoshuttles for Lipid Droplet-Targeted Drug-Resistant Theranostics. 用于脂滴靶向耐药治疗的苯丙酸功能化酞菁硅j聚集纳米穿梭体的合理设计。

IF 9.6 2区医学

Advanced Healthcare Materials Pub Date : 2025-10-03 DOI: 10.1002/adhm.202502542

Yating Shen, Jingtang Wang, Congyi Peng, Guizhi Chen, Wanting Wu, Xinyi Wu, Kuizhi Chen, Kun Wang, Yiru Peng

{"title":"Rational Design of Probenecid-Functionalized Silicon Phthalocyanine J-Aggregated Nanoshuttles for Lipid Droplet-Targeted Drug-Resistant Theranostics.","authors":"Yating Shen, Jingtang Wang, Congyi Peng, Guizhi Chen, Wanting Wu, Xinyi Wu, Kuizhi Chen, Kun Wang, Yiru Peng","doi":"10.1002/adhm.202502542","DOIUrl":"https://doi.org/10.1002/adhm.202502542","url":null,"abstract":"Probenecid, a clinical uricosuric agent with emerging therapeutic potential via membrane protein modulation, is covalently integrated with piperazine silicon phthalocyanine to construct a multifunctional theranostics, propanesulfonylpiperazine silicon phthalocyanine (PP-SiPc), for precise photodynamic therapy (PDT). Through intermolecular π-π stacking, polar interactions, and hydrophobic effects, PP-SiPc self-assembled into J-aggregated nanoshuttles (N-PP-SiPc) that exhibit enhanced UV/Vis absorption, intensified fluorescence, and superior photostability compared to the free form of PP-SiPc. N-PP-SiPc demonstrates high specificity for lipid droplets (LDs), enabling dynamic tracking and discrimination between lysosomal and non-lysosomal LDs-a critical capability for identifying drug-induced lipidosis associated with abnormal accumulation of non-lysosomal LDs. Furthermore, N-PP-SiPc exhibits rapid cellular internalization, improved targeting of LDs, and enhanced light-triggered reactive oxygen species (ROS) generation. These properties collectively contributed to potent PDT efficacy against both cancer cells and drug-resistant strains, underscoring its potential as a theranostic platform capable of overcoming resistance mechanisms. This work establishes a blueprint for developing transporter-modulated theranostic nanomaterials offering organelle-level diagnostic precision.","PeriodicalId":113,"journal":{"name":"Advanced Healthcare Materials","volume":" ","pages":"e02542"},"PeriodicalIF":9.6,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145211170","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

3D Printing Strategies for Bioengineering Human Cornea. 生物工程人类角膜的3D打印策略。

IF 9.6 2区医学

Advanced Healthcare Materials Pub Date : 2025-10-02 DOI: 10.1002/adhm.202502767

Yunong Yuan, Khoon S Lim, Gerard Sutton, Gordon G Wallace, Jingjing You

{"title":"3D Printing Strategies for Bioengineering Human Cornea.","authors":"Yunong Yuan, Khoon S Lim, Gerard Sutton, Gordon G Wallace, Jingjing You","doi":"10.1002/adhm.202502767","DOIUrl":"https://doi.org/10.1002/adhm.202502767","url":null,"abstract":"Over 4.2 million people worldwide suffer from vision impairment related to corneal diseases, with the shortage of donor corneas limiting surgical interventions. The development of 3D printing provides a promising solution for corneal tissue engineering, offering precise control over dimensionality, structural organization, and cell-matrix interactions. The choice of biomaterials and printing strategies critically determines the properties of 3D-printed corneal constructs. While prior reviews have summarized general bioinks and techniques, few have addressed cornea-specific benchmarks such as transparency, curvature, and mechanical robustness. This review provides a comprehensive discussion on the current study of 3D printed cornea, with a focus on replicating the biomechanical and optical properties of native human cornea. Key limitations in current fabrication methods are outlined, and recent advancements in 3D bioprinting technologies-many of which have been successfully applied in other tissue engineering contexts-are reviewed for their potential in producing anisotropic, multilayered corneal constructs with high resolution and fidelity. 3D printing human cornea is believed to have strong potential in generating scalable and clinically relevant solutions to overcome the global donor cornea tissue shortage, and 3D printing holds a central role in their development.","PeriodicalId":113,"journal":{"name":"Advanced Healthcare Materials","volume":" ","pages":"e02767"},"PeriodicalIF":9.6,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145211150","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A Galactose-Engineered Dual-Responsive Nanocarrier for ASO/CRISPR-Cas9 Delivery to Inhibit HBV Replication. 半乳糖工程双响应纳米载体ASO/CRISPR-Cas9递送抑制HBV复制

IF 9.6 2区医学

Advanced Healthcare Materials Pub Date : 2025-10-02 DOI: 10.1002/adhm.202502835

Liuxian Chen, Qin Huang, Yongjie Liu, Ke Chen, Qing Yang, Hua Tang, Dan Wang, Zhenrong Tang

{"title":"A Galactose-Engineered Dual-Responsive Nanocarrier for ASO/CRISPR-Cas9 Delivery to Inhibit HBV Replication.","authors":"Liuxian Chen, Qin Huang, Yongjie Liu, Ke Chen, Qing Yang, Hua Tang, Dan Wang, Zhenrong Tang","doi":"10.1002/adhm.202502835","DOIUrl":"https://doi.org/10.1002/adhm.202502835","url":null,"abstract":"Complete hepatitis B virus (HBV) cure is hindered primarily by the stable persistence of covalently closed circular DNA (cccDNA). Gene editing approaches to eradicate HBV by targeting cccDNA face challenges and limitations due to suboptimal editing efficiency and substantial off-target effects. Herein, a combinatorial therapeutic strategy is developed that integrates CRISPR/Cas9-mediated cccDNA disruption with an antisense oligonucleotide (ASO)-targeted degradation of pregenomic RNA (pgRNA). To overcome delivery challenges, a hepatocyte-targeting nanocarrier (UACPG) is engineered, featuring low immunogenicity, high payload capacity, and dual-stimuli responsiveness. The UACPG platform enabled liver-specific delivery through surface-conjugated targeting ligands, followed by on-demand release of Cas9 ribonucleoprotein complexes and ASO via RNase H-dependent degradation and near-infrared (NIR) light activation. The results demonstrated that UACPG can effectively reduce HBV replication and viral antigen levels, while significantly lowering cccDNA in hydrodynamic HBV-infected mouse models, with no significant off-target effects observed. This nanocarrier achieved the spatiotemporally controlled release of gene-editing systems in vitro and in vivo, significantly inhibiting the replication of HBV, thereby establishing an innovative technological platform for developing curative HBV therapies.","PeriodicalId":113,"journal":{"name":"Advanced Healthcare Materials","volume":" ","pages":"e02835"},"PeriodicalIF":9.6,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145211075","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

YAP Expression Confers Therapeutic Vulnerability to Cuproptosis in Breast Cancer Cells by Regulating Copper Homeostasis. YAP表达通过调节铜稳态赋予乳腺癌细胞治疗性铜退化易感性。

IF 9.6 2区医学

Advanced Healthcare Materials Pub Date : 2025-10-02 DOI: 10.1002/adhm.202502769

Zei-Wei Liu, Cheng-Ying Chu, Yu-Ling Chen, Chu-Hung Chung, Fwu-Long Mi, Ming-Hua Ho, Wen-Jing Hsu, Ming-Yi Hsieh, Ming-Chen Chiang, Cheng-Jui Huang, Pei-Wei Shueng, Ching-Chieh Yang, Chi-Ching Lee, Cheng-Wei Lin

{"title":"YAP Expression Confers Therapeutic Vulnerability to Cuproptosis in Breast Cancer Cells by Regulating Copper Homeostasis.","authors":"Zei-Wei Liu, Cheng-Ying Chu, Yu-Ling Chen, Chu-Hung Chung, Fwu-Long Mi, Ming-Hua Ho, Wen-Jing Hsu, Ming-Yi Hsieh, Ming-Chen Chiang, Cheng-Jui Huang, Pei-Wei Shueng, Ching-Chieh Yang, Chi-Ching Lee, Cheng-Wei Lin","doi":"10.1002/adhm.202502769","DOIUrl":"https://doi.org/10.1002/adhm.202502769","url":null,"abstract":"Copper metabolism plays a complex role in tumor growth and cancer progression and thus holds potential as a therapeutic target. However, reliable diagnostic markers and therapeutic tools for successfully predicting personalized treatment outcomes with copper inhibition remain elusive. In this study, it is discovered that Yes-associated protein (YAP) expression conferred susceptibility toward cuproptosis. Molecular analyses revealed that YAP inhibition significantly abolished cuproptotic characteristics. Interestingly, YAP inhibition does not affect protein lipoylation but disrupts copper homeostasis. Mechanistically, YAP regulates antioxidant-1 (ATOX1), a copper chaperone, and overexpression of ATOX1 restored cuproptotic sensitivity in YAP-silenced cells. To advance copper-targeting therapy, it is identified that melatonin inhibited YAP signaling and attenuated the expression of copper metabolism-related genes. Furthermore, a copper-based functional nanomaterial, EsMP@Fu is developed, which incorporates melatonin and the cuproptosis inducer elesclomol complex with copper ions (Cu(II)) (Es:Cu). This formulation facilitates cuproptotic cytotoxicity via fucoidan-decorated nanocarrier to enhance the targeted delivery toward tumor cells. In vivo study demonstrated that EsMP@Fu significantly suppressed tumor growth by 60%, with more pronounced effects on distant metastasis and the induction of antitumor immunity. Collectively, the findings demonstrate that YAP overexpression confers sensitivity and therapeutic vulnerability to cuproptosis induction, presenting a promising strategy for precision medicine through tailored copper-based therapy.","PeriodicalId":113,"journal":{"name":"Advanced Healthcare Materials","volume":" ","pages":"e02769"},"PeriodicalIF":9.6,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145211078","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0