Advanced Therapeutics最新文献_第6页

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 靶向VEGF-A的免疫功能小鼠间充质胶质母细胞瘤模型可提高正常脑组织分步放疗后的抗肿瘤性并降低促炎反应

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

Lipopeptide 01 from Staphylococcus Epidermidis Resists Pathogenic Bacteria and Promotes Bone Healing in Implant-Associated Infections 表皮葡萄球菌脂肽01抵抗病原菌并促进种植体相关感染的骨愈合

IF 3.7 4区医学

Advanced Therapeutics Pub Date : 2025-01-19 DOI: 10.1002/adtp.202400477

Shengjie Wang, Wei Liu, Chao Yang, Changwei Li, Xianlong Zhang

{"title":"Lipopeptide 01 from Staphylococcus Epidermidis Resists Pathogenic Bacteria and Promotes Bone Healing in Implant-Associated Infections","authors":"Shengjie Wang, Wei Liu, Chao Yang, Changwei Li, Xianlong Zhang","doi":"10.1002/adtp.202400477","DOIUrl":"https://doi.org/10.1002/adtp.202400477","url":null,"abstract":"Implant-associated infections (IAI) present a significant clinical challenge. Effective prevention of and recovery from IAI is complex, involving antibacterial treatment and the promotion of bone integration. However, the current artificial implants used in clinics often lack effective antibacterial properties and have limited functionality. In this study, Lipopeptide 01 (LP01), a lipopeptide derived from the skin commensal Staphylococcus epidermidis is successfully immobilized, onto the porous surface of sulfonated Poly (ether-ether-ketone) (SPEEK) to create a novel artificial implant, LP01-PS. Both in vivo and in vitro experiments demonstrates that LP01-PS displays favorable material properties, biocompatibility, outstanding antibacterial characteristics, and the ability to promote bone formation. Mechanistically, LP01-PS enhances antibacterial activities by triggering TLR2/P65 signaling, upregulating the expression of LL37 and β-defensins in macrophages. Furthermore, it can boost the osteogenic differentiation capability of bone marrow mesenchymal stem cells (BMSCs) through the β-catenin signaling pathway, thereby facilitating bone formation. The discovery of LP01-PS with dual antibacterial and osteogenic effects, coupled with insights into its mode of action, suggests that LP01-PS can serve as a promising implant material to enhance the success rates of total joint replacement surgeries, mitigate the risks of infection and prosthetic loosening, and foster the repair and regeneration of bone tissue.","PeriodicalId":7284,"journal":{"name":"Advanced Therapeutics","volume":"8 5","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-01-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143945046","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

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

Pathophysiology of IBD as a Key Strategy for Polymeric Nanoparticle Development IBD的病理生理是聚合物纳米颗粒开发的关键策略

IF 3.7 4区医学

Advanced Therapeutics Pub Date : 2025-01-19 DOI: 10.1002/adtp.202400439

Elena Gardey, Johannes C. Brendel, Andreas Stallmach

{"title":"Pathophysiology of IBD as a Key Strategy for Polymeric Nanoparticle Development","authors":"Elena Gardey, Johannes C. Brendel, Andreas Stallmach","doi":"10.1002/adtp.202400439","DOIUrl":"https://doi.org/10.1002/adtp.202400439","url":null,"abstract":"Inflammatory bowel disease (IBD) is a complex chronic inflammatory disorder of the gastrointestinal (GI) tract with an uncertain etiology. Currently, IBD therapy relies on the induction of clinical remission followed by maintenance therapy using anti-inflammatory drugs and immunosuppressants; however, a definite cure of the disease is still out of scope. Established approaches are characterized by adverse drug-related side effects that can even be potentially life-threatening. In contrast, increased interest and remarkable scientific progress in targeted drug delivery systems offer a promising approach to reduce systemic adverse events, delivering the therapeutic substances only to inflamed tissue. All alteration in gastrointestinal barrier integrity, especially a disturbed epithelial barrier, a unique pattern of the receptors on cell surface and/or an oxidative stress milieu in inflamed areas can be used as effective approaches for targeted and controlled drug delivery. Hence, this review focuses on the pathophysiology of the inflamed GI tract as a potential strategy for targeted polymeric nanoparticles for IBD treatment. Interdisciplinary efforts between the polymeric chemistry and gastroenterology/immunology promise to create novel synergies that improve the development of effective nanoparticle systems with significant clinical impact. In this regard, the current challenges in the clinical translation of promising nanomedicine are also discussed.","PeriodicalId":7284,"journal":{"name":"Advanced Therapeutics","volume":"8 3","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.202400439","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143645782","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) 脑血管疾病药物控释系统（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

引用次数: 0

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) 姜黄素和盐酸苄胺复合纳米颗粒治疗外阴阴道念珠菌病：从发展到体外和体内生物学应用（ad . 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

引用次数: 0

Issue Information (Adv. Therap. 1/2025) 发布信息（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 近红外响应MTX-Mn3O4@PDA纳米递送系统对类风湿关节炎的治疗效果

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

Recent Advances in Promoting Bone Regeneration in Type 2 Diabetes Using Drug Delivery Vehicles and Vehicle-Free Therapeutics 利用药物输送载体和无载体疗法促进 2 型糖尿病患者骨再生的最新进展

IF 3.7 4区医学

Advanced Therapeutics Pub Date : 2025-01-12 DOI: 10.1002/adtp.202400400

Yasamin Pesaran Afsharian, Mostafa Rahimnejad, Sayed Mahmood Rabiee, Farideh Feizi, Hermann Seitz

{"title":"Recent Advances in Promoting Bone Regeneration in Type 2 Diabetes Using Drug Delivery Vehicles and Vehicle-Free Therapeutics","authors":"Yasamin Pesaran Afsharian, Mostafa Rahimnejad, Sayed Mahmood Rabiee, Farideh Feizi, Hermann Seitz","doi":"10.1002/adtp.202400400","DOIUrl":"https://doi.org/10.1002/adtp.202400400","url":null,"abstract":"The incidence of type 2 diabetes (T2DM) increases significantly worldwide. Due to consistent hyperglycemia, insulin resistance, and chronic inflammation, T2DM patients encounter osteoporosis and induced osteoporotic fracture risks. Antidiabetic drugs have been traditional therapies that seek to control blood glucose, balance bone metabolism, and favor systemic immunosuppression. However, such drugs impact bone quality and its nano-scale features in the long-term. Today, biomedical experts are continuously advancing drug delivery tools for local delivery of osteo-immunomodulatory agents in T2DM. It is demonstrated that bioavailability and release profile determine osteo-immunomodulatory and osteoconductivity outcomes of such therapeutics. This review focuses on introducing currently used local drug delivery vehicles in T2DM. The fabrication techniques of such biomaterial-based systems are thoroughly examined. Furthermore, the feasibility and the potential factors contributing to consistent release of bioactive agents are surveyed. Furthermore, the extent of in vivo responses is described in the context of current research examples. Targeted signaling mechanisms are also assessed in detail to elucidate the activated healing routes.","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":"143397111","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