Advanced Therapeutics最新文献_第4页

Genetic Engineering Methods in Primary T Cells 原代T细胞的基因工程方法

IF 2.6 4区医学

Advanced Therapeutics Pub Date : 2025-07-09 DOI: 10.1002/adtp.202500149

Anthony Youssef, Hui-Shan Li

引用次数: 0

Fibronectin-Functionalized Tea Polyphenol Nanoparticles Loaded with Ferrostatin-1 for Synergistic Abdominal Aortic Aneurysms Therapy 负载铁他汀-1的纤维连接蛋白功能化茶多酚纳米颗粒协同治疗腹主动脉瘤

IF 2.6 4区医学

Advanced Therapeutics Pub Date : 2025-07-06 DOI: 10.1002/adtp.202500179

Hongyu Zhang, Bohai Li, Xin Li, Changjiang Yu, Ruixin Fan

{"title":"Fibronectin-Functionalized Tea Polyphenol Nanoparticles Loaded with Ferrostatin-1 for Synergistic Abdominal Aortic Aneurysms Therapy","authors":"Hongyu Zhang, Bohai Li, Xin Li, Changjiang Yu, Ruixin Fan","doi":"10.1002/adtp.202500179","DOIUrl":"10.1002/adtp.202500179","url":null,"abstract":"Abdominal aortic aneurysm (AAA) is a life-threatening cardiovascular condition with complex pathophysiology, for which effective pharmacological treatments are currently lacking. Recently, ferroptosis has been identified as a key mechanism of vascular smooth muscle cell (VSMC) death, emerging as a potential therapeutic target for mitigating aortic aneurysms. Here, a drug-delivery nanoparticle system combining tea polyphenol-based nanoparticles and a ferroptosis inhibitor is developed. This system, formed through the oxidative polymerization and self-assembly of epigallocatechin gallate (EGCG), efficiently encapsulates Ferrostatin-1 (Fer-1) during self-assembly and is subsequently functionalized with fibronectin (FN) for targeted treatment of angiotensin II-induced AAA. Both in vitro and in vivo experiments demonstrated that TPN-Fer-1@FN effectively inhibits ferroptosis, suppresses the inflammatory response, and reduces matrix degradation, while preserving the normal contractile function of VSMCs and modulating the NOTCH3 signaling pathway. Moreover, the TPN-Fer-1@FN nanosystem exhibited low toxicity and good biocompatibility. These findings suggest that TPN-Fer-1@FN represents a promising therapeutic strategy for inhibiting ferroptosis and modulating the pathological processes underlying AAA.","PeriodicalId":7284,"journal":{"name":"Advanced Therapeutics","volume":"8 8","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144832786","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Consolidation of Ultrasound and Light: Silicon Phthalocyanine-Based Sensitizer Therapeutic Agent for Synergetic Sonodynamic–Photodynamic Therapy of Breast Cancer 超声与光的巩固：基于酞菁硅的增敏剂治疗剂用于声动力-光动力协同治疗乳腺癌

IF 2.6 4区医学

Advanced Therapeutics Pub Date : 2025-07-06 DOI: 10.1002/adtp.202500053

Hilal Çakmak, Aysegul Turkkol, Umut Kerem Kolac, Göknur Yaşa Atmaca, Aleksey E. Kuznetsov, M. Serdar Çavuş, Mustafa Z. Yıldız, Lukasz Sobotta, Mehmet Dincer Bilgin, Ali Erdoğmuş, Emre Güzel

{"title":"Consolidation of Ultrasound and Light: Silicon Phthalocyanine-Based Sensitizer Therapeutic Agent for Synergetic Sonodynamic–Photodynamic Therapy of Breast Cancer","authors":"Hilal Çakmak, Aysegul Turkkol, Umut Kerem Kolac, Göknur Yaşa Atmaca, Aleksey E. Kuznetsov, M. Serdar Çavuş, Mustafa Z. Yıldız, Lukasz Sobotta, Mehmet Dincer Bilgin, Ali Erdoğmuş, Emre Güzel","doi":"10.1002/adtp.202500053","DOIUrl":"10.1002/adtp.202500053","url":null,"abstract":"Sono-photodynamic therapy (SPDT), a useful technique applied in combination with photodynamic therapy (PDT) and sonodynamic therapy (SDT), reduces potential side effects compared to monotherapy. This study reports the photochemical and sono-photochemical properties and in vitro analysis of silicon (IV) phthalocyanine (SiPc), with a particular focus on its efficiency in singlet oxygen production. When photochemical investigations are conducted alone, the SiPc Φ∆ value is measured as 0.68; however, when light and ultrasound are combined, the value increased by 25% to 0.85 in sono-photochemical studies. The Q-band of the calculated SiPc UV–vis spectrum is found to be in very good agreement with the experimental data, with the computed oscillator strengths (the absorption intensities) for Q-band being higher than for B-band. Furthermore, the therapeutic effects of PDT and SPDT using SiPc are evaluated in MCF-7 and MDA-MB-231 breast cancer cell lines. The results demonstrated that SPDT, combining light and ultrasound, significantly enhanced cytotoxicity compared to PDT alone. Additionally, SPDT triggered pyroptosis, characterized by upregulation of NLRP3, CASP1, IL1B, and IL18, revealing a distinct mechanism of cell death. These findings suggest that SiPc-mediated SPDT amplifies oxidative stress and activates multiple cell death pathways, offering a promising and targeted approach for improving breast cancer therapy.","PeriodicalId":7284,"journal":{"name":"Advanced Therapeutics","volume":"8 8","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144832688","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Microphysiological Systems in Cancer Research: Advancing Immunotherapy through Tumor Microenvironment-Integrated Organ-On-Chip Models 癌症研究中的微生理系统：通过肿瘤微环境集成器官芯片模型推进免疫治疗

IF 2.6 4区医学

Advanced Therapeutics Pub Date : 2025-07-04 DOI: 10.1002/adtp.202500098

Fabiana Moresi, Francesco Noto, Jyothsna Vasudevan, Xavier Bisteau, Giulia Adriani, Andrea Pavesi

{"title":"Microphysiological Systems in Cancer Research: Advancing Immunotherapy through Tumor Microenvironment-Integrated Organ-On-Chip Models","authors":"Fabiana Moresi, Francesco Noto, Jyothsna Vasudevan, Xavier Bisteau, Giulia Adriani, Andrea Pavesi","doi":"10.1002/adtp.202500098","DOIUrl":"10.1002/adtp.202500098","url":null,"abstract":"The intricate tumor microenvironment (TME) poses a significant barrier to effective cancer immunotherapy, requiring innovative strategies to model and address its challenges. Traditional models, such as 2D cultures and animal studies, often fail to capture the TME's dynamic, multicellular, and spatially complex nature, limiting their predictive power for therapeutic outcomes. To overcome these limitations, this review examines innovative microphysiological systems (MPS) that enhance the understanding of tumor-immune interactions and pave the way for more effective immunotherapeutic strategies. First the complex features of the TME and its key players are detailed, elaborating on their dynamic interplay with tumors. Importantly, it is highlighted how these components contribute to treatment resistance, offering crucial insights into therapeutic failures. Then, state-of-the-art 3D in vitro organ-on-chip (OoC) models are presented that faithfully recapitulate the TME, incorporating patient-derived tumors to enhance clinical relevance. These advanced systems not only overcome the limitations of traditional animal models and 2D cultures but also provide a robust platform for assessing and improving immunotherapeutic regimens. By bridging the gap between bench and bedside, MPS promises to accelerate the development of novel, more effective immunotherapies for solid tumors, potentially transforming cancer treatment in the near future.","PeriodicalId":7284,"journal":{"name":"Advanced Therapeutics","volume":"8 9","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://advanced.onlinelibrary.wiley.com/doi/epdf/10.1002/adtp.202500098","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145100854","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Immuno-Engineering in the AI Era: From Fundamental Research to Clinical Translation 人工智能时代的免疫工程：从基础研究到临床转化

IF 2.6 4区医学

Advanced Therapeutics Pub Date : 2025-07-02 DOI: 10.1002/adtp.202500087

Meng Zhu, Andy Tay, Xianlei Li

{"title":"Immuno-Engineering in the AI Era: From Fundamental Research to Clinical Translation","authors":"Meng Zhu, Andy Tay, Xianlei Li","doi":"10.1002/adtp.202500087","DOIUrl":"10.1002/adtp.202500087","url":null,"abstract":"Artificial intelligence (AI) plays a pivotal role in advancing immune engineering, a field aimed at developing personalized therapies for cancer, autoimmune diseases, and infections. AI is overcoming significant challenges in immune engineering, such as immune system complexity, patient-specific variability, and the dynamic interactions within the immune microenvironment. This perspective highlights how AI is bridging the gap between laboratory research and clinical application through three major pillars: 1) Mechanistic Decoding, where AI integrates multi-omics data to understand immune system complexity and predict molecular interactions; 2) Therapeutic Innovation, where AI designs personalized immunotherapies, such as optimizing antibody-antigen binding and immune receptor dynamics; and 3) Clinical Acceleration, where AI enhances clinical trial designs, speeds up drug development, and adjusts therapies in real-time based on patient responses. Further discussion addresses algorithmic bias, data privacy, and the need for global standards in AI-powered decision-making, ethical and regulatory challenges. AI is not only enabling breakthroughs in immune engineering but also paving the way for customized immune-based therapies. It ensures that the technologies are applied responsibly and equitably in clinical practice.","PeriodicalId":7284,"journal":{"name":"Advanced Therapeutics","volume":"8 9","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145101006","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Topology and Mechanism of Broadband and Fast Multi-Characteristic Opsin for Neuromodulation 宽带和快速多特征视蛋白的神经调节拓扑结构和机制

IF 2.6 4区医学

Advanced Therapeutics Pub Date : 2025-07-02 DOI: 10.1002/adtp.202500009

Samarendra Mohanty, Pratyajit Mohapatra, Amir Singh, William Marks, Subrata Batabyal, Michael Carlson, Najam Sharif, Sanghoon Kim

{"title":"Topology and Mechanism of Broadband and Fast Multi-Characteristic Opsin for Neuromodulation","authors":"Samarendra Mohanty, Pratyajit Mohapatra, Amir Singh, William Marks, Subrata Batabyal, Michael Carlson, Najam Sharif, Sanghoon Kim","doi":"10.1002/adtp.202500009","DOIUrl":"10.1002/adtp.202500009","url":null,"abstract":"Optogenetics has enabled targeted manipulation of neural circuits, offering insights into the intricacies of brain function and paving the way for potential therapeutic applications in neurological disorders. Multi-characteristic Opsin (MCO) is an optogenetics therapy candidate that is undergoing multiple clinical trials, including randomized control trials. However, its cellular topography and mechanism of action have remained unknown. Here, we reveal the biophysical characteristics of the MCO molecule, including its unique structure and function, using a combination of predictive protein modeling, western blotting-based protease protection assay, and electrophysiology. MCO’s first extracellular subunit forms a cation-channel pore, while the second subunit is partially embedded in the membrane, extending to the third intracellular cytoplasmic subunit. Functional studies using whole-cell recordings showed that MCO is activated by broadband visible light with fast on-off kinetics with high photosensitivity, and large dynamic range across the visible spectrum, enabling best-in-class light-activation of MCO-expressing cells. Further, multi-electrode array recording confirmed multi-color light-activation of MCO-expressing neurons in the retina. The unique topological and functional activation features of fused MCO protein represent novel findings linking the in-vitro and in-vivo efficacy of this opsin, which is particularly important for neuromodulation leading to vision restoration in retinal degenerative diseases and other neurological therapies.","PeriodicalId":7284,"journal":{"name":"Advanced Therapeutics","volume":"8 8","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144832811","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

RNA-Based Therapeutics: Cutting-Edge Advances in Clinical Research rna疗法：临床研究的前沿进展

IF 2.6 4区医学

Advanced Therapeutics Pub Date : 2025-07-01 DOI: 10.1002/adtp.202500082

Débora Ferreira, Ligia R. Rodrigues

{"title":"RNA-Based Therapeutics: Cutting-Edge Advances in Clinical Research","authors":"Débora Ferreira, Ligia R. Rodrigues","doi":"10.1002/adtp.202500082","DOIUrl":"10.1002/adtp.202500082","url":null,"abstract":"Over the years, the relevance of gene therapy has increased as an alternative to conventional drugs. Pharmaceutical industries have been directing their efforts toward the creation of novel gene-based therapies for a broad range of diseases. RNA-based therapeutics can efficiently trigger gene silencing and, despite the initial research setbacks, this technology laid the groundwork for advancements in RNA-based drug design that ultimately contributed to the remarkably rapid advance of messenger RNA (mRNA) vaccines to combat the COVID-19 pandemic. In light of this information, RNA medicines are currently well-positioned to have a noteworthy impact in clinical practice. Various RNA medicines have received clinical approval, while others are still in the research phase or undergoing preclinical trials. In this review, an overview of RNA-based therapeutics is aimed to provide, including antisense oligonucleotides and RNA interference-based mechanisms, mRNA-encoded approaches, aptamers, and clustered regularly interspaced short palindromic repeats (CRISPR-Cas)-mediated genome editing. Furthermore, the commonly used chemistries in drug delivery systems and strategies for targeting specific cells, as well as the key nanocarriers used in RNA loading, are explored. The main advances and current challenges will be thoroughly summarized.","PeriodicalId":7284,"journal":{"name":"Advanced Therapeutics","volume":"8 8","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144832320","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Fungal Keratitis: Clinical Presentations, Mechanism and Management Strategies 真菌性角膜炎：临床表现、机制和治疗策略

IF 2.6 4区医学

Advanced Therapeutics Pub Date : 2025-06-30 DOI: 10.1002/adtp.202500247

Min Wang, Manwen Yang, Hang Yin, Zhen Li, Xianwen Wang, Lei Shi

引用次数: 0

Optimization of the Isolation Method for Large-Scale Production of Synthetic Bacterial Vesicles for Cancer Immunotherapy 大规模生产肿瘤免疫治疗合成细菌囊泡分离方法的优化

IF 2.6 4区医学

Advanced Therapeutics Pub Date : 2025-06-26 DOI: 10.1002/adtp.202500084

Negar Ordouzadeh, Rossella Crescitelli, Agnes Zimmer, Petra Tjärnlund, Cecilia Lässer, Jan Lötvall, Kyong-Su Park

{"title":"Optimization of the Isolation Method for Large-Scale Production of Synthetic Bacterial Vesicles for Cancer Immunotherapy","authors":"Negar Ordouzadeh, Rossella Crescitelli, Agnes Zimmer, Petra Tjärnlund, Cecilia Lässer, Jan Lötvall, Kyong-Su Park","doi":"10.1002/adtp.202500084","DOIUrl":"10.1002/adtp.202500084","url":null,"abstract":"Bacterial vesicles have emerged as therapeutic drug candidates to treat a wide range of diseases, including cancer. However, critical concerns remain regarding their safety, in view of inducing systemic inflammation. To address this, semi-synthetic bacterial vesicles (SyBV) have recently been developed, directly derived from bacterial cell membranes. These vesicles have reduced toxicity but retained immunomodulatory ability, which is important for immuno-oncology purposes. In this study, the manufacturing process of SyBV has been further refined to meet Good Manufacturing Practice (GMP) standards. Multiple steps are reconsidered in the optimized method, including adaptation of centrifugation steps, benzonase treatment, and elimination of sonication steps, thereby producing a new set of optimized SyBV, designated as SyBVOpti. Similarly to SyBV isolated using the previous protocol, SyBVOpti do not activate macrophages but stimulate dendritic cells to produce IL-12 in a dose-dependent manner—moreover, these vesicles attenuate tumor growth in vivo in a model of malignant melanoma. Further, the optimized process applies to a GMP-compatible Escherichia coli source for producing SyBVOpti under GMP conditions. Collectively, these findings describe a reliable technique for large-scale production of SyBV with preserved therapeutic potential, allowing GMP manufacturing and translation of these bioactive vesicles into clinical practice.","PeriodicalId":7284,"journal":{"name":"Advanced Therapeutics","volume":"8 8","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://advanced.onlinelibrary.wiley.com/doi/epdf/10.1002/adtp.202500084","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144832974","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Rewiring Neuroimmunity: Nanoplatform Innovations for CNS Disease Therapy 神经免疫重组：中枢神经系统疾病治疗的纳米平台创新

IF 2.6 4区医学

Advanced Therapeutics Pub Date : 2025-06-25 DOI: 10.1002/adtp.202500124

Muhammad Usman Akbar, Weiwei Guo, Xin Shen, Yimeng Fang, Yilin Liu, Peng-Yuan Wang, Roey Elnathan, Yaping Chen

{"title":"Rewiring Neuroimmunity: Nanoplatform Innovations for CNS Disease Therapy","authors":"Muhammad Usman Akbar, Weiwei Guo, Xin Shen, Yimeng Fang, Yilin Liu, Peng-Yuan Wang, Roey Elnathan, Yaping Chen","doi":"10.1002/adtp.202500124","DOIUrl":"10.1002/adtp.202500124","url":null,"abstract":"Central nervous system (CNS) diseases pose a significant global health challenge, currently affecting one in six individuals worldwide. Despite extensive research into their molecular and cellular mechanisms, effective treatment remains elusive due to the inherent complexity of CNS disorders and the protective constraints of the blood-brain barrier (BBB).Conventional monotherapies often fail to produce satisfactory outcomes. In recent years, nanomaterials have emerged as promising therapeutic platforms—offering enhanced pharmacokinetics, improved biodistribution, and reduced systemic toxicity. More importantly, multifunctional nanomaterials can be engineered to actively target the brain parenchyma and lesion sites, co-deliver multiple therapeutics, and modulate neuroimmune responses synergistically. Their tunability and adaptability to diverse pathological contexts make them well-suited to address the multifactorial nature of CNS diseases. This review discusses the mechanisms contributing to therapeutic resistance in common brain disorders and highlights the potential of engineered nanomaterials that can address the multifaceted disease microenvironment. We also identify current challenges and prospects for the rational design of multifunctional nanoplatforms tailored to CNS disease treatment.","PeriodicalId":7284,"journal":{"name":"Advanced Therapeutics","volume":"8 9","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://advanced.onlinelibrary.wiley.com/doi/epdf/10.1002/adtp.202500124","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145102253","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0