Advanced Therapeutics最新文献_第2页

Revolutionizing Precision Medicine: Unveiling Smart Stimuli-Responsive Nanomedicine 革新精准医学：揭示智能刺激反应纳米医学

IF 2.6 4区医学

Advanced Therapeutics Pub Date : 2025-07-17 DOI: 10.1002/adtp.202500073

Ayushi Taneja, Himanshu Sekhar Panda, Jiban Jyoti Panda, Thakur Gurjeet Singh, Avneet Kour

{"title":"Revolutionizing Precision Medicine: Unveiling Smart Stimuli-Responsive Nanomedicine","authors":"Ayushi Taneja, Himanshu Sekhar Panda, Jiban Jyoti Panda, Thakur Gurjeet Singh, Avneet Kour","doi":"10.1002/adtp.202500073","DOIUrl":"10.1002/adtp.202500073","url":null,"abstract":"Smart stimuli-responsive nanomaterials have emerged as promising candidates in pharmaceutical delivery due to their ability to react to diverse physical, chemical, and biological stimuli. These systems can be precisely engineered to release therapeutic agents in response to specific internal cues, allowing for controlled and targeted interventions tailored to individual patient conditions. Their nanoscale architecture, ease of surface modification, and multifunctional physicochemical properties further enhance their suitability for biomedical applications. Recent advances underscore their potential in treating complex and chronic diseases such as cancer, neurological disorders, and inflammatory conditions, where conventional therapies often fall short. By integrating these responsive nanotechnologies into precision medicine, it is possible to enhance therapeutic efficacy while minimizing systemic toxicity. Herein, this work highlights the ongoing progress in the development and application of stimuli-responsive nanomedicines. This work also emphasizes the need for extensive clinical validation to determine their long-term safety and effectiveness in human subjects.","PeriodicalId":7284,"journal":{"name":"Advanced Therapeutics","volume":"8 8","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144833015","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

Spatiotemporal Control of IL-12 Delivery Improves Its Efficacy in Treatment of Solid Tumors 时空控制IL-12的传递提高其治疗实体瘤的疗效

IF 2.6 4区医学

Advanced Therapeutics Pub Date : 2025-07-16 DOI: 10.1002/adtp.202500077

Jonathan C. Su, Garrett M. Kelly, Joshua J. Milligan, Sonal Deshpande, Rachel L. Strader, Max R. Ney, Nikhil Peterson, Parul Sirohi, Shaily Pal, Lance W. Lindsey, Daniel M. Shapiro, Xinghai Li, Ashutosh Chilkoti

{"title":"Spatiotemporal Control of IL-12 Delivery Improves Its Efficacy in Treatment of Solid Tumors","authors":"Jonathan C. Su, Garrett M. Kelly, Joshua J. Milligan, Sonal Deshpande, Rachel L. Strader, Max R. Ney, Nikhil Peterson, Parul Sirohi, Shaily Pal, Lance W. Lindsey, Daniel M. Shapiro, Xinghai Li, Ashutosh Chilkoti","doi":"10.1002/adtp.202500077","DOIUrl":"10.1002/adtp.202500077","url":null,"abstract":"Despite renewed interest in IL-12 as a cancer immunotherapy due to its ability to stimulate the adaptive immune system, its short half-life and narrow therapeutic window continues to present challenges for effective delivery. Previous studies with IL-12 have investigated the effects of route of delivery or sustained delivery of the cytokine on its efficacy but are unable to simultaneously investigate the effects of both within the same system. This work seeks to address this gap by utilizing an elastin-like polypeptide (ELP) carrier, which can undergo a thermally triggered phase transition to a gel-like depot, to probe the effects of both sustained release and spatial delivery of IL-12. By conjugating IL-12 with an ELP, this work creates an IL-12-ELP fusion that can be injected intratumorally or subcutaneously to form a sustained-release depot. In a B16F10 murine model, intratumoral injection of a depot-forming IL-12-ELP fusion significantly improved survival compared to free IL-12. IL-12-ELP is retained within the tumor approximately fourfold longer than free IL-12, resulting in higher CD8+ T cell recruitment at the tumor and local concentrations of inflammatory cytokines at Day 2. Taken together, this work provides insights into rational cytokine delivery, the importance of tumor localization, and the benefits of sustained release.","PeriodicalId":7284,"journal":{"name":"Advanced Therapeutics","volume":"8 8","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144832642","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

Cytokine mRNA Delivery and Local Immunomodulation in the Placenta Using Lipid Nanoparticles 细胞因子mRNA在胎盘中的传递和局部免疫调节

IF 2.6 4区医学

Advanced Therapeutics Pub Date : 2025-07-16 DOI: 10.1002/adtp.202500148

Samuel I. Hofbauer, Luisa A. Fink, Rachel E. Young, Tara Vijayakumar, Katherine M. Nelson, Nia Bellopede, Mohamad-Gabriel Alameh, Drew Weissman, Jason P. Gleghorn, Rachel S. Riley

{"title":"Cytokine mRNA Delivery and Local Immunomodulation in the Placenta Using Lipid Nanoparticles","authors":"Samuel I. Hofbauer, Luisa A. Fink, Rachel E. Young, Tara Vijayakumar, Katherine M. Nelson, Nia Bellopede, Mohamad-Gabriel Alameh, Drew Weissman, Jason P. Gleghorn, Rachel S. Riley","doi":"10.1002/adtp.202500148","DOIUrl":"10.1002/adtp.202500148","url":null,"abstract":"During pregnancy, the maternal immune system adapts to balance tolerance of the semi-allogenic fetus while protecting the fetus from pathogens. Dysregulated immune activity at the maternal–fetal interface contributes to pregnancy complications, such as recurrent pregnancy loss and preeclampsia. Compared to healthy placentas, preeclamptic placentas exhibit increased pro-inflammatory signaling, including a predominance of inflammatory macrophages, leading to impaired tissue remodeling and restricted blood flow. However, the precise mechanisms driving this immune imbalance remain poorly understood, in part due to the lack of tools to probe individual pathways. Here, lipid nanoparticles (LNPs) are used to deliver cytokine-encoded mRNA to placental cells, called trophoblasts, enabling local immunomodulation. LNP-mediated delivery of IL-4 and IL-13 mRNA induced cytokine secretion by trophoblasts, leading to polarization of primary human monocytes toward anti-inflammatory phenotypes. Notably, lowering the mRNA dose increased expression of alternatively-activated macrophage markers, revealing an inverse relationship between dose and polarization status. Intravenous injection of LNPs in pregnant mice achieves placental secretion of IL-4 and IL-13 with minimal changes to pro-inflammatory cytokines in the serum. These findings establish LNPs as tools for local immunomodulation in the placenta, offering a strategy to study and treat immune dysfunction in pregnancy and in other inflammatory conditions.","PeriodicalId":7284,"journal":{"name":"Advanced Therapeutics","volume":"8 8","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://advanced.onlinelibrary.wiley.com/doi/epdf/10.1002/adtp.202500148","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144833303","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

Liquiritin Exerts a Dual Effect on BMSCs Osteogenic Differentiation and Fracture Healing by Activating the ERK/JNK Pathway and Providing Antioxidant Protection 甘草素通过激活ERK/JNK通路和提供抗氧化保护，对骨髓间充质干细胞成骨分化和骨折愈合具有双重作用

IF 2.6 4区医学

Advanced Therapeutics Pub Date : 2025-07-16 DOI: 10.1002/adtp.202400552

Haijun Mao, Jing Liu, Juan Feng, Yalikun Yusufu, Lei Yang, Qing Jiang, Minghui Sun

{"title":"Liquiritin Exerts a Dual Effect on BMSCs Osteogenic Differentiation and Fracture Healing by Activating the ERK/JNK Pathway and Providing Antioxidant Protection","authors":"Haijun Mao, Jing Liu, Juan Feng, Yalikun Yusufu, Lei Yang, Qing Jiang, Minghui Sun","doi":"10.1002/adtp.202400552","DOIUrl":"10.1002/adtp.202400552","url":null,"abstract":"Liquiritin, a flavonoid from Glycyrrhiza uralensis L., has diverse pharmacological properties, but its impact on fracture healing is unexplored. This study investigates its osteogenic and antioxidative effects on bone marrow mesenchymal stem cells (BMSCs) in vitro and its regenerative effect on rat femoral fractures in vivo. Cytotoxicity is assessed via MTT assay, and osteogenic differentiation via ALP and ARS staining. A rat femoral fracture model validates its therapeutic effects, with micro-CT and histological assessments evaluating healing outcomes. Gene and protein expression in osteogenic and signaling pathways are analyzed through RT-qPCR, western blot, and immunofluorescence. ROS levels are measured using DCFH-DA staining. Results show liquiritin enhances osteogenesis in BMSCs, evidenced by increased ALP activity and calcium deposition. In rats, it facilitates bone regeneration and upregulates phosphorylated ERK and JNK. Additionally, it reduces ROS generation post-oxidative injury, boosting NRF2, HO1, and NQO1 expression.","PeriodicalId":7284,"journal":{"name":"Advanced Therapeutics","volume":"8 8","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://advanced.onlinelibrary.wiley.com/doi/epdf/10.1002/adtp.202400552","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144833302","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

One-Step Freeze Drying Strategy for Scalable Production of Small Extracellular Vesicles Derived From Mesenchymal Stem Cells 间充质干细胞细胞外小泡规模化生产的一步冷冻干燥策略

IF 2.6 4区医学

Advanced Therapeutics Pub Date : 2025-07-13 DOI: 10.1002/adtp.202500121

Yashvi Sharma, Meenakshi Mendiratta, Suchi Gupta, Sonali Rawat, Pardeep Kumar Vaishnav, Sujata Mohanty

{"title":"One-Step Freeze Drying Strategy for Scalable Production of Small Extracellular Vesicles Derived From Mesenchymal Stem Cells","authors":"Yashvi Sharma, Meenakshi Mendiratta, Suchi Gupta, Sonali Rawat, Pardeep Kumar Vaishnav, Sujata Mohanty","doi":"10.1002/adtp.202500121","DOIUrl":"10.1002/adtp.202500121","url":null,"abstract":"The clinical translation of mesenchymal stem cell-derived small extracellular vesicles (MSC-sEV) holds immense promise due to their regenerative and immunomodulatory properties. However, their widespread application is hindered by challenges in storage, stability, and cold chain transport. In this study, it is explored lyophilisation as a strategy to extend the shelf life of MSC-sEV while maintaining their structural integrity and biological functionality. Lyophilised sEV are stored at four different temperatures—room temperature (RT), 4, −20°C, and −80 °C—for durations of 1, 3, and 6 months. This findings reveal that normal refrigeration temperature of 4 °C storage is suitable for maintaining sEV stability for up to 1 month, while −20°C and −80 °C are more effective for longer durations, preserving sEV integrity and functionality for 6 months and beyond. These results underscore the importance of optimizing storage protocols for lyophilised MSC-sEV to ensure their viability for clinical and research applications. This study establishes a foundation for improved storage and cold chain transport of MSC-sEV, paving the way for their integration into scalable and standardized therapeutic platforms.","PeriodicalId":7284,"journal":{"name":"Advanced Therapeutics","volume":"8 8","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-07-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144833203","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

Issue Information (Adv. Therap. 7/2025) 发行信息（ad . Therap. 7/2025）

IF 2.6 4区医学

Advanced Therapeutics Pub Date : 2025-07-10 DOI: 10.1002/adtp.70023

引用次数: 0

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