Advanced Therapeutics最新文献

Self-Assembled Nanocarriers of Synthetic and Natural Plasmalogens for Potential Nanomedicine Development (Adv. Therap. 2/2025)

IF 3.7 4区医学

Advanced Therapeutics Pub Date : 2025-02-13 DOI: 10.1002/adtp.202570004

Yu Wu, Borislav Angelov, Yuru Deng, Takehiko Fujino, Md Shamim Hossain, Thomas Bizien, Angelina Angelova

引用次数: 0

Issue Information (Adv. Therap. 2/2025)

IF 3.7 4区医学

Advanced Therapeutics Pub Date : 2025-02-13 DOI: 10.1002/adtp.202570005

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Eltrombopag Inhibited Liver Cancer by Enhancing SMYD4 Protein Degradationvia TRIP12 Ubiquitinase

IF 3.7 4区医学

Advanced Therapeutics Pub Date : 2025-02-03 DOI: 10.1002/adtp.202400372

Jiale Li, Qiqiang Zhang, Chunyan Wang, Shupeng Liu

{"title":"Eltrombopag Inhibited Liver Cancer by Enhancing SMYD4 Protein Degradationvia TRIP12 Ubiquitinase","authors":"Jiale Li, Qiqiang Zhang, Chunyan Wang, Shupeng Liu","doi":"10.1002/adtp.202400372","DOIUrl":"https://doi.org/10.1002/adtp.202400372","url":null,"abstract":"According to prior studies, SET and MYND domain-containing protein 4 (SMYD4) is involved in tumor progression and metastasis, representing a potential therapeutic target for tumors. However, no specific inhibitors or drugs targeting SMYD4 are currently available. In this study, molecular docking and molecular dynamics simulations were used to screen small molecule lead compounds binding to SMYD4 protein. CCK8 assay, colony formation assay, EdU assay were used to analyze the viability and proliferation of tumor cells. Flow cytometric analysis was used to evaluate cell apoptosis and cell cycle. Clorazepate, Ativan, Darifenacin and Eltrombopag were found to bind with SMYD4 with the highest probability and to meet the five principles of the drug class. Molecular dynamics simulations showed that Eltrombopag had the strongest binding capacity to SMYD4 protein. The functional analysis showed that Eltrombopag inhibited hepatocellular carcinoma cell proliferation and promoted apoptosis in vivo and in vitro at low density. Moreover, Eltrombopag enhanced ubiquitination of SMYD4 protein and promoted its degradation via thyroid hormone receptor interactor 12(TRIP12). These findings suggest that Eltrombopag is a potential inhibitor of SMYD4 protein, representing a novel leading compound for SMYD4 and applied for tumor treatment.","PeriodicalId":7284,"journal":{"name":"Advanced Therapeutics","volume":"8 2","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143396757","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

Targeting VEGF-A in an Immunocompetent Orthotopic Mouse Model of Mesenchymal Glioblastoma Improves Antitumorigenicity and Decreases Proinflammatory Response in Normal Brain Tissue after Fractionated Radiotherapy

IF 3.7 4区医学

Advanced Therapeutics Pub Date : 2025-01-23 DOI: 10.1002/adtp.202400374

Alexander Edward Nieto, Daniel Felix Fleischmann, Kristian Unger, Valerie Albrecht, Jessica Maas, Horst Zitzelsberger, Claus Belka, Martin Proescholdt, Kirsten Lauber, Maximilian Niyazi, Michael Orth

{"title":"Targeting VEGF-A in an Immunocompetent Orthotopic Mouse Model of Mesenchymal Glioblastoma Improves Antitumorigenicity and Decreases Proinflammatory Response in Normal Brain Tissue after Fractionated Radiotherapy","authors":"Alexander Edward Nieto, Daniel Felix Fleischmann, Kristian Unger, Valerie Albrecht, Jessica Maas, Horst Zitzelsberger, Claus Belka, Martin Proescholdt, Kirsten Lauber, Maximilian Niyazi, Michael Orth","doi":"10.1002/adtp.202400374","DOIUrl":"https://doi.org/10.1002/adtp.202400374","url":null,"abstract":"Glioblastoma is the most aggressive primary brain tumor characterized by a dismal prognosis and a profound therapy resistance that is most evident for the mesenchymal molecular subtype of glioblastoma. Targeting vascular endothelial growth factor (VEGF)-A by the monoclonal antibody bevacizumab, despite failing to improve survival in randomized trials, yields relevant benefits in glioblastoma patients such as reduction of radionecrosis, an adverse event associated with radiotherapy. This demands for continued research to identify optimal combinations of anti-VEGF-A and standard therapies for glioblastoma treatment. We show here that blocking VEGF-A in an immune competent orthotopic glioblastoma mouse model resembling the adverse mesenchymal molecular subtype increases the tumoricidal effect of computed tomography (CT)-based fractionated radiotherapy and also rectifies irradiation-induced expression of genes with known association to mesenchymal subtype enrichment as revealed by microarray-based transcriptome analyses of explanted tumors. VEGF-A blockade also decreases the expression of myeloid-cell-related gene patterns in irradiated tumors and lowers inflammatory response in normal brain tissue after tumor irradiation. Hence, these data both provide a hint how blockade of VEGF-A increases the effect of radiotherapy in mesenchymal glioblastoma and a mechanistic base for clinical observations reporting reduced incidences of radionecrosis in glioblastoma patients treated with radiotherapy upon concurrent administration of bevacizumab.","PeriodicalId":7284,"journal":{"name":"Advanced Therapeutics","volume":"8 2","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/adtp.202400374","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143397349","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

Disease-Adaptive Drug Delivery to the Inflamed Intestinal Mucosa Using Poly(Lactic-Co-Glycolic Acid)-cyclodextrin Hybrid Nanocarriers 利用聚（乳酸-共聚甘醇酸）-环糊精混合纳米载体向炎症肠黏膜进行疾病适应性给药

IF 3.7 4区医学

Advanced Therapeutics Pub Date : 2025-01-19 DOI: 10.1002/adtp.202400368

Jonas Schreiner, Felix E. B. Brettner, Sebastian Steigert, Annika Haessler, Raf Mols, Stefanie Gier, Nathalie Jung, Sarah Vogel-Kindgen, Susanne Muschert, Patrick Augustijns, Maike Windbergs

{"title":"Disease-Adaptive Drug Delivery to the Inflamed Intestinal Mucosa Using Poly(Lactic-Co-Glycolic Acid)-cyclodextrin Hybrid Nanocarriers","authors":"Jonas Schreiner, Felix E. B. Brettner, Sebastian Steigert, Annika Haessler, Raf Mols, Stefanie Gier, Nathalie Jung, Sarah Vogel-Kindgen, Susanne Muschert, Patrick Augustijns, Maike Windbergs","doi":"10.1002/adtp.202400368","DOIUrl":"https://doi.org/10.1002/adtp.202400368","url":null,"abstract":"Fluctuating severity of symptoms is a common hallmark of many inflammatory disorders, including inflammatory bowel disease (IBD). Addressing the pH changes during active and resting phases in IBD-affected tissue, a disease-adaptive nanocarrier system is designed for oral administration, enabling pH-dependent local drug release. The hybrid carrier combines poly(lactic-co-glycolic acid) and an amphiphilic cyclodextrin derivative, with physicochemical properties and drug release kinetics controlled by adjusting polymer ratios. The systems exhibited baseline drug release at pH 5 with increased rates at pH 2, which is characteristic of actively inflamed IBD tissue. Assessing the impact of biomolecule adhesion, biocorona formation was studied using ex vivo human intestinal fluids. Corona composition highly depended on the patient's prandial state and the nanocarrier matrix, with proteins predominating in the fasted state and lipids in the fed state. Notably, differences in the attachment of proteins and free fatty acids are detected in the latter. Transport studies using human in vitro models of the inflamed intestine revealed mucosal accumulation, facilitating localized drug delivery and effectively reducing cytokine levels to basal concentrations. This hybrid system highlights the potential of disease-adaptive drug release for inflammatory disease treatment and underscores the impact of biocorona formation on therapeutic performance in the gastrointestinal tract.","PeriodicalId":7284,"journal":{"name":"Advanced Therapeutics","volume":"8 2","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-01-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/adtp.202400368","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143396861","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

Full Disappearance of PC3-Luc Prostate Tumors Mediated by Hyperthermia Under Low Intensity Ultrasound Application in the Presence of Magnetosomes 在磁小体存在的情况下应用低强度超声波，通过热疗促使 PC3-Luc 前列腺肿瘤完全消失

IF 3.7 4区医学

Advanced Therapeutics Pub Date : 2025-01-19 DOI: 10.1002/adtp.202400281

Cynthia El Hedjaj, Eric Barret, Imène Chebbi, Raphaël Le Fèvre, Caroline Maake, Franco Guscetti, François Guyot, Jean-Francois Aubry, Olivier Seksek, Edouard Alphandéry

{"title":"Full Disappearance of PC3-Luc Prostate Tumors Mediated by Hyperthermia Under Low Intensity Ultrasound Application in the Presence of Magnetosomes","authors":"Cynthia El Hedjaj, Eric Barret, Imène Chebbi, Raphaël Le Fèvre, Caroline Maake, Franco Guscetti, François Guyot, Jean-Francois Aubry, Olivier Seksek, Edouard Alphandéry","doi":"10.1002/adtp.202400281","DOIUrl":"https://doi.org/10.1002/adtp.202400281","url":null,"abstract":"Iron oxide nanoparticles have been proposed for magnetic hyperthermia treatment of tumors. However, efficacy depends on the injection of large amounts of such nanoparticles and the equipment is costly. Here, a new thermal cancer treatment is described, in which a tumor containing a low concentration of nonpyrogenic pure iron oxide nanominerals coated with carboxy-methyl-dextran (M-CMD), corresponding to modified magnetosomes, are exposed to ultrasound. Heating PC3 prostate carcinoma cells between 43 and 46°C using ultrasound in the presence of M-CMD resulted in significant necrotic cell death. Furthermore, deposition of M-CMD containing 3 µg of iron per mm3 of tumor in subcutaneous xenografts of PC3-Luc tumors of 150 mm3 followed by 6 to 10 sessions of ultrasound application (1 W cm−2, 1 MHz) of 10 min each led to a tumor temperature of 43–46°C per session and to total tumor disappearance without regrowth over 6 months following treatment start. Sequential histological analyses of the tumor tissues revealed partial tumor occupation by M-CMD and an increase in cell death over time. Neither lesions, nor magnetosome accumulation were found in microscopic sections of various internal organs collected from treated mice euthanized 6 months after the beginning of the treatment, indicating that M-CMD may not lead to long-term side effects.","PeriodicalId":7284,"journal":{"name":"Advanced Therapeutics","volume":"8 2","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-01-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/adtp.202400281","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143396860","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

Controlled Drug Release Systems for Cerebrovascular Diseases (Adv. Therap. 1/2025)

IF 3.7 4区医学

Advanced Therapeutics Pub Date : 2025-01-13 DOI: 10.1002/adtp.202570001

Celia Martín-Morales, Sofia Caspani, Manuel Desco, Célia Tavares de Sousa, María Victoria Gómez-Gaviro

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Hybrid Nanoparticles Dual-Loaded With Curcumin and Benzydamine Hydrochloride for the Treatment of Vulvovaginal Candidiasis: From Development to Biological Application In Vitro and In Vivo (Adv. Therap. 1/2025)

IF 3.7 4区医学

Advanced Therapeutics Pub Date : 2025-01-13 DOI: 10.1002/adtp.202570003

Gabriela C. Carvalho, Maria Nolasco Viseu Domingues, Gabriel Davi Marena, Ermei Mäkilä, Jiachen Li, Gésinda Geertsema-Doornbusch, Cleverton Roberto de Andrade, Marc C. A. Stuart, Mohammad-Ali Shahbazi, Ione Corrêa, Brandon W. Peterson, Jarno Salonen, Helena F. Florindo, Taís Maria Bauab, Marlus Chorilli, Hélder A. Santos

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Issue Information (Adv. Therap. 1/2025)

IF 3.7 4区医学

Advanced Therapeutics Pub Date : 2025-01-13 DOI: 10.1002/adtp.202570002

引用次数: 0

Therapeutic Effect of a Near-Infrared Responsive MTX-Mn3O4@PDA Nano-Delivery System on Rheumatoid Arthritis

IF 3.7 4区医学

Advanced Therapeutics Pub Date : 2025-01-12 DOI: 10.1002/adtp.202400345

Xinwei Zhang, Ziping Wang, Yu Bai, Yulun Hu, Qing Chen, Yueping Liu, Mingming Chang

{"title":"Therapeutic Effect of a Near-Infrared Responsive MTX-Mn3O4@PDA Nano-Delivery System on Rheumatoid Arthritis","authors":"Xinwei Zhang, Ziping Wang, Yu Bai, Yulun Hu, Qing Chen, Yueping Liu, Mingming Chang","doi":"10.1002/adtp.202400345","DOIUrl":"https://doi.org/10.1002/adtp.202400345","url":null,"abstract":"Rheumatoid arthritis (RA) is an autoimmune disease associated with chronic inflammatory processes. RA, which is typically associated with the accumulation of hyperactive immune cells (HICs), particularly M1 proinflammatory macrophages, is accompanied by elevated levels of reactive oxygen species (ROS) and decreased pH in the synovial membranes of the joints. In this work, a nano-delivery system (MTX-Mn3O4@PDA) is designed that can deliver photothermal materials, ROS scavengers, and synovial fibroblast inhibitors at the joint site for the treatment of RA. After injecting MTX-Mn3O4@PDA into the inflamed site of RA, photothermal therapy is initiated by near-infrared (NIR) laser irradiation, which resulted in the death of activated inflammatory cells at the lesion site. While polydopamine (PDA) slowly dissociates under stimulation by a low pH microenvironment. Subsequently, excess ROS interacts with the Mn3O4 nanozyme and the undissociated PDA nanozyme, promoting ROS clearance, while Methotrexate (MTX) inhibits the proliferation of synovial fibroblasts. Intra-articular injection of MTX-Mn3O4@PDA (7 mg kg−1) into collagen-induced arthritis mice demonstrated efficacy in reducing toe swelling and significantly alleviating synovial inflammation, bone erosion, and cartilage degeneration. This nano-delivery system has potential clinical applications for treating RA.","PeriodicalId":7284,"journal":{"name":"Advanced Therapeutics","volume":"8 2","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-01-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143397112","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